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  • CLASSES

    Selective Serotonin Reuptake Inhibitor Antidepressants, SSRIs

    BOXED WARNING

    Children, growth inhibition, suicidal ideation

    Citalopram is not FDA approved for any indication in children. In October 2004, the FDA directed manufacturers of all antidepressants to include a boxed warning detailing the risk of suicide in pediatric patients. A causal role has been established for antidepressants in inducing suicidality in pediatric patients. The risk of suicidality for these drugs was identified in a pooled analysis of 24 placebo-controlled trials (n = 4,400) lasting up to 16 weeks in pediatric patients with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders. The analysis showed a greater risk of suicidality during the first few months of treatment in those receiving antidepressants (SSRIs and others). The average risk of such events on drug was 4% and 2% for placebo; however, no suicides occurred in these trials. Pooled analysis of short-term clinical trials during early phase treatment with SSRIs and other antidepressants in young adults (18 to 24 years) also showed an increased risk of suicidal thinking and behavior. The clinical need for an antidepressant in children or young adults for any use must be weighed against the risk of increased suicidality; patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior, particularly within the first few months of starting therapy or at the time of dose increase or decrease. It is unknown if the suicidality risk in children and young adults extends to longer-term therapy (i.e., beyond several months). The possibility of a suicide attempt is inherent in patients with depressive symptoms, whether these occur in primary depression or in association with another primary disorder such as OCD. All patients with a history of suicidal ideation or behaviors and those with a prominence of suicidal ideation prior to treatment are considered at an increased risk for suicidal ideation or attempts, and should be closely monitored during treatment with citalopram. In patients who exhibit changes in symptoms, worsening of depression or emergent suicidality, a decision should be made to change or discontinue treatment. If discontinuing, the medication should be tapered as rapidly as possible, but with recognition that abrupt discontinuation can also cause adverse symptoms. All antidepressants should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose. The potential for growth inhibition in pediatric patients should be monitored during SSRI therapy. Monitor height and weight periodically while the patient is receiving citalopram. Data are inadequate to determine whether the chronic use of SSRIs causes long-term growth inhibition; however, decreased weight gain has been observed in children and adolescents receiving citalopram.

    DEA CLASS

    Rx

    DESCRIPTION

    Selective serotonin reuptake inhibitor (SSRI)
    Indicated in adults for the treatment of depression; no approved uses in pediatrics
    Known risk of QT prolongation; increased risk of suicidality in pediatric and young adult patients at treatment initiation and changes

    COMMON BRAND NAMES

    Celexa

    HOW SUPPLIED

    Celexa/Citalopram/Citalopram Hydrobromide Oral Sol: 5mL, 10mg
    Celexa/Citalopram/Citalopram Hydrobromide Oral Tab: 10mg, 20mg, 40mg

    DOSAGE & INDICATIONS

    For the treatment of major depression.
    For the treatment of major depression in adult patients.
    Oral dosage
    Adults 60 years and younger

    Initially, 20 mg PO once daily. Titrate in increments of 20 mg at intervals of no less than one week. Max: 40 mg/day in the general population and 20 mg/day in poor metabolizers of CYP2C19 due to the potential for QT prolongation. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Acute episodes of depression usually require several months or longer of sustained pharmacologic therapy. Whether the dose needed to induce remission is identical to the dose needed for maintenance is unknown. Antidepressant efficacy of SSRIs in adults is maintained for up to 1 year of active treatment.

    Adults older than 60 years

    20 mg PO once daily is the recommended and maximum dosage. Higher dosages are not recommended due to an association with QT prolongation. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    For the treatment of major depression† in pediatric patients.
    Oral dosage
    Children and Adolescents 7 to 17 years

    10 mg PO once daily initially. Some experts recommend initial doses of 20 mg/day PO in those 12 years and older, and a few pediatric studies have used this higher starting dose in patients as young as 7 years. Clinical practice guidelines recommend starting with a low dose and titrating gradually, in 10 mg/day increments at 4-week intervals until clinical response is achieved. Some studies have reported titration as often as every week. A dose of 20 mg/day PO is considered effective; reported mean dose range is 20 to 25 mg PO per day. Max: 40 mg/day in the general population and 20 mg/day in poor metabolizers of CYP2C19 due to the potential for QT prolongation. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Patients with minimal or no response after 8 weeks of treatment will likely need alternative treatment. Continuation of medication for 6 to 12 months after symptom remission is recommended; those who require further maintenance therapy should be periodically reassessed to determine the need for ongoing treatment.

    For the treatment of social phobia (social anxiety disorder)†.
    Oral dosage
    Children and Adolescents 8 to 17 years

    10 mg PO once daily initially, followed by titration to response and tolerability. Data are extremely limited. In one small, open-label pilot study combining pharmacologic with psychotherapeutic interventions, 12 patients received an initial citalopram dose of 10 mg/day PO followed by upward titration to a maximum of 40 mg/day based upon response and tolerability. Nine children completed the study (12 weeks). Based on clinician global ratings of change, 41.7% of subjects were very much improved and 41.7% were much improved. No subjects worsened. At study end, the mean dosage was 35 mg/day. Patients should be periodically reassessed to determine the need for ongoing maintenance treatment. Max: 40 mg/day in the general population and 20 mg/day in poor metabolizers of CYP2C19 due to the potential for QT prolongation. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    For the treatment of obsessive-compulsive disorder (OCD)†.
    Oral dosage
    Adults 60 years and younger

    Initially, 20 mg PO once daily; may increase to 40 mg PO once daily after 1 week. In an open pilot study, 40 to 60 mg PO once daily alleviated symptoms of OCD in 76% of patients. Max: 40 mg/day in the general population and 20 mg/day in poor metabolizers of CYP2C19 due to the potential for QT prolongation. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Geriatric Adults older than 60 years

    The recommended and maximum daily dose is 20 mg/day PO. Higher dosages are not recommended due to an association with QT prolongation. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Children and Adolescents 6 to 17 years

    10 mg PO once daily initially, followed by titration based on response and tolerability. Data are extremely limited. Results from small open-label studies suggest a possible role of citalopram in the treatment of childhood OCD. In one study, citalopram was initiated at 10 mg/day PO followed by titration based upon response and tolerability to a maximum dose of 20 mg/day PO in children (6 years of age and older) and 30 mg/day PO in adolescents. Ninety-three percent of participants were considered responders according to the primary efficacy measure (CY-BOCS). In a separate study, doses of 10 to 40 mg/day PO were effective in 75% of participating children and adolescents (9 years of age and older). Patients should be periodically reassessed to determine the need for ongoing maintenance treatment. Max: 40 mg/day in the general population and 20 mg/day in poor metabolizers of CYP2C19 due to the potential for QT prolongation. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    For the treatment of panic disorder† (with or without agoraphobia).
    Oral dosage
    Adults 60 years and younger

    20 to 60 mg PO once daily has been used in published studies. Higher dosages (i.e., 40 to 60 mg per day) appear to be no more effective than lower dosages (i.e., 20 to 30 mg per day). Max: 40 mg/day in the general population and 20 mg/day in poor metabolizers of CYP2C19 due to the potential for QT prolongation. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Geriatric Adults older than 60 years

    The maximum recommended daily dose is 20 mg/day PO. Higher dosages are not recommended due to an association with QT prolongation. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    For the treatment of posttraumatic stress disorder (PTSD)†.
    Oral dosage
    Adults 60 years and younger

    20 to 60 mg PO once daily has been used in clinical studies. Pilot studies indicate that citalopram may be effective for a wide variety of traumatic stressors, including combat. Max: 40 mg/day in the general population and 20 mg/day in poor metabolizers of CYP2C19 due to the potential for QT prolongation. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Geriatric Adults older than 60 years

    The maximum daily dose is 20 mg/day PO. Higher dosages are not recommended due to an association with QT prolongation. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Adolescents

    Data are limited. One open study has suggested that 20 mg/day PO is effective. Max: 40 mg/day in the general population and 20 mg/day in poor metabolizers of CYP2C19 due to the potential for QT prolongation. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    For the treatment of premenstrual dysphoric disorder (PMDD)†.
    Oral dosage
    Adult females

    20 mg PO once daily (range: 10 to 30 mg PO once daily) as a target dose during the luteal phase is more effective than placebo in treating marked pre-menstrual irritability. Luteal phase dosing is as effective as continuous administration of similar doses; data are limited by the small study size. SSRIs as a class are considered effective in reducing the symptoms of PMDD, such as irritability, depressed mood, and carbohydrate cravings, whether taken in the luteal phase only or continuously. Adverse effects are relatively frequent and dose-related, the most common being nausea and asthenia. Citalopram is the less commonly studied SSRI for this condition. Max: 40 mg/day in the general population and 20 mg/day in poor metabolizers of CYP2C19 due to the potential for QT prolongation. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    For the treatment of hot flashes† in women experiencing symptoms of menopause†.
    Oral dosage
    Adult females 60 years and younger

    Initially 10 mg PO once daily with titration to 20 to 30 mg PO once daily, if tolerated. In 29 patients ranging in age from 34 to 82 years who did not respond to venlafaxine for the treatment of hot flashes, 4 weeks of citalopram was associated with a reduction in hot flash score (assesses both frequency and intensity) to 47% of baseline (p < 0.001). The frequency of hot flashes was reduced by 45% (p < 0.001) compared to baseline. In another study, 9 months in duration, fluoxetine or citalopram was not associated with a reduction in hot flash frequency or severity; however, citalopram was associated with an improvement in insomnia. Further studies are needed to confirm these findings. Max: 40 mg/day in the general population and 20 mg/day in poor metabolizers of CYP2C19 due to the potential for QT prolongation. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Geriatric Adult females older than 60 years

    Initially 10 mg PO once daily with titration to 20 to 30 mg PO once daily, if tolerated, has been used. Dosages above 20 mg/day are not recommended in those over 60 years of age due to an association with QT prolongation. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In 29 patients ranging in age from 34 to 82 years who did not respond to venlafaxine for the treatment of hot flashes, 4 weeks of citalopram was associated with a reduction in hot flash score (assesses both frequency and intensity) to 47% of baseline (p < 0.001). The frequency of hot flashes was reduced by 45% (p < 0.001) compared to baseline. In another study, 9 months in duration, fluoxetine or citalopram was not associated with a reduction in hot flash frequency or severity; however, citalopram was associated with an improvement in insomnia. Further studies are needed to confirm these findings.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    60 years and younger: 40 mg/day PO in the general population and 20 mg/day PO in poor metabolizers of CYP2C19.
    Older than 60 years: 20 mg/day PO.

    Geriatric

    20 mg/day PO.

    Adolescents

    Safety and efficacy have not been established; however, doses up to 40 mg/day PO have been used off-label for depression and anxiety disorders. Do not exceed 20 mg/day PO in poor metabolizers of CYP2C19.

    Children

    6 to 12 years: Safety and efficacy have not been established; however, doses up to 40 mg/day PO have been used off-label for depression and anxiety disorders. Do not exceed 20 mg/day PO in poor metabolizers of CYP2C19.
    1 to 5 years: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Citalopram 20 mg PO once daily is the recommended maximum dose in adults with hepatic impairment, due to the risk of QT prolongation. There are no guidelines available for pediatric patients. Child-Pugh classification is a poor predictor of the need for dosage adjustment based on data from clinical trials.

    Renal Impairment

    CrCl >= 20 mL/minute: No dosage adjustment is necessary.
    CrCl < 20 mL/minute: Use caution; specific guidelines for dosage adjustments are not available due to lack of available data.
     
    Intermittent hemodialysis
    Citalopram is unlikely to be significantly removed by hemodialysis given its large volume of distribution. Use caution; specific guidelines for dosage adjustments are not available due to lack of available data.

    ADMINISTRATION

    Oral Administration

    May be administered in the morning or evening, with or without food.
    A Med Guide is available that provides information about the risks of antidepressant use. The Med Guide should be dispensed with each new and refilled prescription.

    Oral Solid Formulations

    Orally disintegrating tablets: Remove tablet from blister pack just prior to administration; once removed, it cannot be stored. Open blister pack by peeling back the foil. Do not push tablet through foil. After removing from blister pack, the tablet should be placed in the mouth where it will dissolve within seconds and can then be swallowed with saliva. May be taken with or without water or food. Do not chew, break, or split the tablets.

    Oral Liquid Formulations

    Oral solution: Measure dosage with an oral syringe or calibrated measuring device.

    STORAGE

    Celexa:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Citalopram hypersensitivity, escitalopram hypersensitivity

    Citalopram is contraindicated in patients with a citalopram hypersensitivity or hypersensitivity to any of the formulation components. Escitalopram is the active isomer of racemic citalopram; therefore, the 2 drugs should not be taken together as this would constitute duplicative therapy. Cross-sensitivity with citalopram should be anticipated in patients with an escitalopram hypersensitivity.

    Abrupt discontinuation

    Avoid abrupt discontinuation of any SSRI if possible. Gradual tapering is recommended during discontinuation of citalopram to decrease or prevent the occurrence of potential discontinuation symptoms. The most frequent SSRI discontinuation symptoms include dizziness, vertigo, nausea, vomiting, flu-like symptoms, sensory disturbances (e.g., paresthesias, electric shock sensation), sleep disturbances, irritability, anxiety, and/or agitation. Discontinuation symptoms are more likely to occur after withdrawal of SSRIs with a short half-life such as paroxetine.

    Bipolar disorder, mania

    All effective antidepressants can transform depression into mania or hypomania in predisposed individuals. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. If a patient develops symptoms suggestive of mania, citalopram should be held and the appropriate therapy to treat the manic symptoms initiated. Additionally, depression may be the presenting symptom of a mixed/manic episode of bipolar disorder. Patients should be adequately screened for bipolar disorder prior to initiating an antidepressant. Such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. Patients with depression or comorbid depression in the setting of other psychiatric illness being treated with antidepressants should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes. Caregivers should be advised to closely observe the patient on a daily basis and to communicate immediately with the prescriber the emergence of agitation, irritability, unusual changes in behavior, or suicidality. It should be noted that citalopram is not approved for use in treating bipolar depression.

    Children, growth inhibition, suicidal ideation

    Citalopram is not FDA approved for any indication in children. In October 2004, the FDA directed manufacturers of all antidepressants to include a boxed warning detailing the risk of suicide in pediatric patients. A causal role has been established for antidepressants in inducing suicidality in pediatric patients. The risk of suicidality for these drugs was identified in a pooled analysis of 24 placebo-controlled trials (n = 4,400) lasting up to 16 weeks in pediatric patients with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders. The analysis showed a greater risk of suicidality during the first few months of treatment in those receiving antidepressants (SSRIs and others). The average risk of such events on drug was 4% and 2% for placebo; however, no suicides occurred in these trials. Pooled analysis of short-term clinical trials during early phase treatment with SSRIs and other antidepressants in young adults (18 to 24 years) also showed an increased risk of suicidal thinking and behavior. The clinical need for an antidepressant in children or young adults for any use must be weighed against the risk of increased suicidality; patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior, particularly within the first few months of starting therapy or at the time of dose increase or decrease. It is unknown if the suicidality risk in children and young adults extends to longer-term therapy (i.e., beyond several months). The possibility of a suicide attempt is inherent in patients with depressive symptoms, whether these occur in primary depression or in association with another primary disorder such as OCD. All patients with a history of suicidal ideation or behaviors and those with a prominence of suicidal ideation prior to treatment are considered at an increased risk for suicidal ideation or attempts, and should be closely monitored during treatment with citalopram. In patients who exhibit changes in symptoms, worsening of depression or emergent suicidality, a decision should be made to change or discontinue treatment. If discontinuing, the medication should be tapered as rapidly as possible, but with recognition that abrupt discontinuation can also cause adverse symptoms. All antidepressants should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose. The potential for growth inhibition in pediatric patients should be monitored during SSRI therapy. Monitor height and weight periodically while the patient is receiving citalopram. Data are inadequate to determine whether the chronic use of SSRIs causes long-term growth inhibition; however, decreased weight gain has been observed in children and adolescents receiving citalopram.

    MAOI therapy

    Citalopram is contraindicated for concomitant use in patients receiving MAOI therapy, due to the risk for serotonin syndrome. Citalopram should not be used in combination with an MAOI, or within 14 days of discontinuing treatment with an MAOI intended to treat psychiatric disorders. Conversely, at least 14 days should be allowed after stopping citalopram before starting an MAOI intended to treat psychiatric disorders. In addition, do not start citalopram in a patient who is being treated with linezolid or intravenous methylene blue. Serotonin syndrome has been reported with SSRIs and SNRIs, including citalopram, both when taken alone, but especially when coadministered with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort). If such symptoms occur, discontinue citalopram and initiate supportive treatment. If concomitant use of citalopram with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.

    Electroconvulsive therapy (ECT), seizure disorder

    Although anticonvulsant effects of citalopram have been observed in animal studies, citalopram has not been systematically evaluated in patients with a history of seizure disorder; initiate therapy with caution. In clinical trials, seizures occurred in 0.3% of patients treated with citalopram and 0.5% of patients treated with placebo. Citalopram's effects during electroconvulsive therapy (ECT) have not been evaluated in clinical studies to date.

    Acute myocardial infarction, alcoholism, bradycardia, cardiac arrhythmias, cardiac disease, coronary artery disease, diabetes mellitus, females, heart failure, hypertension, hypocalcemia, hypokalemia, hypomagnesemia, malnutrition, myocardial infarction, QT prolongation, thyroid disease, torsade de pointes, ventricular tachycardia

    Citalopram causes dose-dependent QT prolongation which, in some cases, has been associated with torsade de pointes (TdP), ventricular tachycardia, and sudden death. Citalopram is not recommended for use in patients with congenital long QT syndrome, bradycardia, hypokalemia, hypomagnesemia, recent acute myocardial infarction, uncompensated heart failure, or in patients receiving medications associated with QT prolongation. However, if citalopram therapy is considered essential under any of these circumstances, electrocardiogram (ECG) monitoring is recommended. Patients at risk for significant electrolyte disturbances should have baseline serum potassium and magnesium measurements with periodic monitoring. Hypokalemia and/or hypomagnesemia should be corrected prior to treatment initiation. Use citalopram with caution in patients with other cardiac disease or other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, heart failure, myocardial infarction, hypertension, coronary artery disease, hypocalcemia, or in patients receiving medications known to cause electrolyte imbalances. Females, elderly patients, patients with diabetes mellitus, thyroid disease, malnutrition, alcoholism, or hepatic impairment may also be at increased risk for QT prolongation. Due to the risk of QT prolongation, a lower maximum daily dose is recommended in adult and elderly patients above 60 years of age, patients with hepatic impairment, and those who are poor metabolizers of CYP2C19 or who are receiving a CYP2C19 inhibitor. Citalopram should be discontinued in patients who experience persistent QTc measurements above 500 milliseconds.

    Dehydration, hyponatremia, hypovolemia

    Selective serotonin reuptake inhibitors (SSRIs), including citalopram, may cause hyponatremia, which is frequently the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). In some cases, serum sodium levels less than 110 mmol/L have been reported; however, the adverse effect appeared reversible upon discontinuation of the causative SSRI. Elderly patients, those receiving diuretics or prone to dehydration, and those who are otherwise volume depleted (e.g., hypovolemia) appear to be at greatest risk. Hyponatremia may manifest as headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness which may result in falls. Severe manifestations include hallucinations, syncope, seizure, coma, respiratory arrest, and death. Symptomatic hyponatremia may require discontinuation of citalopram, as well as implementation of the appropriate medical interventions.

    Renal failure, renal impairment

    Excretion of unchanged citalopram in the urine is a minor route of elimination. No dosage adjustment is necessary for patients with mild or moderate renal impairment. However, citalopram should be used with caution in patients with severe renal impairment (i.e., CrCl less than 20 mL/minute) or renal failure until this population has been evaluated during chronic treatment with citalopram; there are no pharmacokinetic data in these patients.

    Hepatic disease, poor metabolizers

    Citalopram should be used with caution in patients with hepatic disease because the drug is extensively metabolized in the liver, resulting in decreased clearance and increased plasma concentrations in patients with hepatic dysfunction. The maximum recommended dose for adult patients with hepatic impairment is 20 mg/day. Patients who are CYP2C19 poor metabolizers also have reduced clearance, increased maximal plasma concentrations, and increased exposure to citalopram and should also receive reduced dosages. The maximum recommended dose for adult patients who are CYP2C19 poor metabolizers is 20 mg/day.

    Anticoagulant therapy, bleeding, thrombolytic therapy

    Monitor patients taking an SSRI such as citalopram for signs and symptoms of bleeding. Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage). Concurrent use of aspirin, NSAIDs, anticoagulant therapy, thrombolytic therapy, or other medications that enhance bleeding potential may increase this risk. Patients should be instructed to promptly report any bleeding events to the practitioner.

    Bone fractures, osteoporosis

    Use selective serotonin reuptake inhibitors (SSRIs), including citalopram, cautiously in patients with osteoporosis. Epidemiological studies on bone fracture risk following exposure to SSRIs have reported an association between SSRI treatment and bone fractures. It is unknown to what extent fracture risk is directly attributable to SSRI treatment. If an citalopram-treated patient presents with unexplained bone pain, point tenderness, swelling, or bruising, consider the possibility of a fragility fracture. Patients at risk for osteoporosis, such as postmenopausal females, may benefit from more frequent monitoring of bone density during long-term use of an SSRI.

    Closed-angle glaucoma, increased intraocular pressure

    Caution is recommended when prescribing citalopram to patients with closed-angle glaucoma. The pupillary dilation that can occur with antidepressants may precipitate a closed-angle glaucoma attack in patients with anatomically narrow angles who do not have a patent iridectomy. An acute attack of closed-angle glaucoma is considered a medical emergency because the increased intraocular pressure is rapid and severe, and may quickly result in blindness if left untreated.

    Akathisia

    The use of citalopram or other SSRIs has been associated with the development of akathisia, which is characterized by an inner sense of restlessness and psychomotor agitation such as an inability to sit or stand still usually associated with subjective distress. This is most likely to occur within the first few weeks of treatment. It is generally recommended to discontinue SSRI treatment if akathisia occurs.

    Anorexia nervosa

    Decreased appetite and weight loss have been observed during administration of SSRIs. Therefore, caution is advisable when administering citalopram to patients with anorexia nervosa or other conditions where weight loss is undesirable.

    Driving or operating machinery, ethanol ingestion

    Because any psychoactive drug may impair judgment, thinking, or motor skills, patients should use caution when driving or operating machinery, until the full effect of citalopram is determined. Although citalopram has not been shown to increase the impairment of mental and motor skills caused by alcohol, patients should be advised to avoid ethanol ingestion while taking citalopram. Additionally, other coadministered centrally-acting drugs may augment cognitive impairment.

    Neonates, pregnancy

    There are no adequate and well-controlled studies in pregnant women; citalopram should be used in pregnancy only when the benefits to the mother outweigh the potential risk to the fetus. There is some evidence that SSRI use may cause non-teratogenic fetal harm during human pregnancy. Neonates exposed to citalopram and other SSRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Symptoms have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of serotonergic agents or, possibly, a neonatal abstinence syndrome. Epidemiologic reports also suggest a possible association between maternal use of SSRIs after 20 weeks gestation and the development of persistent pulmonary hypertension (PPHN) of the newborn. More recent retrospective studies have not shown an increased risk of PPHN with SSRI exposure. In December 2011, the FDA issued a safety announcement stating that based on conflicting data an increased risk of PPHN from SSRI exposure cannot be determined, and that healthcare professionals should not alter their current practice of treating depression in pregnancy at this time. Women who are pregnant, or are planning a pregnancy, and currently taking citalopram should consult with their physician about whether to continue taking it. When treating a pregnant woman with an SSRI or other serotonergic agent during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. If clinically feasible, gradual tapering of the medication prior to delivery may be considered. A prospective study of pregnant women receiving antidepressant treatment found that only 26% of those maintained on their antidepressant had relapsed versus 68% of those who had discontinued their medication. Increasing evidence suggests an association between antidepressant use during pregnancy and a subsequent diagnosis of autism spectrum disorder (ASD) in the offspring. In 2 separate population based case-control studies, an approximate 2-fold increased risk of autism spectrum disorder was observed. One study found the increased risk was associated only with SSRI use, while the other study found an increased risk associated with use of SSRIs and tricyclic antidepressants. In animal studies, citalopram has been shown to have adverse effects on embryo/fetal and postnatal development, including teratogenic effects, when administered at doses greater than human maximum therapeutic doses. In general, animal studies have shown that SSRIs downregulate the serotonin receptors in the fetal cortex and that these changes can be present for a period of time after birth. The effect of citalopram on labor and delivery is unknown. The National Pregnancy Registry for Psychiatric Medications is dedicated to evaluating the safety of psychiatric medications that may be taken by women during pregnancy to treat a wide range of mood, anxiety, or psychiatric disorders. The primary goal of this Registry is to determine the frequency of major malformations, such as heart defects, cleft lip, or neural tube defects, in babies exposed to various psychiatric drugs during pregnancy. While the research concentrates on atypical antipsychotics and antidepressant use, pregnant women using other psychiatric medications are encouraged to register. For more information, contact the registry at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry or by phone 1-866-961-2388.

    Breast-feeding

    Citalopram should be used with caution in lactating women because of the excretion of the drug into human breast milk. There have been 2 reports of infants experiencing excessive somnolence, decreased feeding, and weight loss in association with breast-feeding from a citalopram-treated mother; in 1 case, the infant was reported to recover completely upon discontinuation of citalopram by the mother and in the second case, no follow-up information was available. Small studies assessing adverse events in infants exposed to citalopram during breast-feeding found no significant difference when compared to infants in control groups. Another published case report has noted infant sleep disturbances; the breast-milk concentrations of citalopram were comparable to those of the maternal serum in this case. Quantifiable levels of citalopram were also noted in the serum of the infant. The sleep disturbance in the infant subsided after dividing the mothers medication in 2 doses daily and replacing 2 of the daily infant feeds with formula. SSRI use during breast-feeding may be of concern. Patients should advise their physician of their intention to breast-feed. If citalopram must be continued during lactation due to the benefit of the drug to the mother, infant breast-feedings should be avoided during the times of maximum maternal serum concentrations (i.e., within 4 hours of the daily dose). Substitution of formula during times of maximal drug concentrations should help limit the potential for adverse effects in the infant. Alternatively, discontinuation of citalopram during lactation or the use of formula for all feeds may be indicated. A pooled analysis found that maternal use of sertraline, along with nortriptyline and paroxetine, usually produced undetectable or low drug concentrations in infant serum and, therefore, may be the preferred antidepressants in breast-feeding mothers. A study assessing the transfer of escitalopram into breast milk concluded that the absolute infant dose of escitalopram was lower than the absolute infant dose of citalopram when breast-feeding mothers were taking equivalent antidepressant doses of the 2 drugs. Consider the benefits of breast-feeding, the risk of potential drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding baby experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Geriatric

    Citalopram should be used with caution in the older adult and geriatric patients more than 60 years of age. Older adults are more likely to have conditions that contribute to lowered serum sodium concentrations, may have lowered clearance of the drug, or may be more sensitive to the drug in general, although clinical use has not revealed any issues concerning the efficacy or overall differences in adverse effects vs. younger adults. Prolongation of the QT interval is a concern at citalopram dosages exceeding recommendations. The maximum dose for geriatric patients more than 60 years of age is 20 mg/day PO.[28269] Despite these cautions, the selective serotonin reuptake inhibitors (SSRIs) are often a preferred antidepressant group for treatment of depression or other behavioral symptoms in the elderly, including patients with dementia.  According to the Beers Criteria, SSRIs are considered potentially inappropriate medications (PIMs) in elderly patients with a history of falls or fractures and should be avoided, unless safer alternatives are not available. SSRIs can produce ataxia, impaired psychomotor function, syncope, and additional falls. If an SSRI must be used, consider reducing the use of other CNS-active medications that increase the risk of falls and fractures and implement other strategies to reduce fall risk. Also, SSRIs can cause or exacerbate hyponatremia and SIADH, and the elderly are at increased risk of developing these conditions. Sodium levels should be closely monitored when starting or changing dosages in older adults.[63923] The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of antidepressants in residents of long-term care facilities; treatment duration should follow recommendations of pertinent literature and clinical practice guidelines for the condition treated. Monitor treated patients closely for worsening of depression and suicidal behavior or thinking, especially during initiation of therapy and during dose changes. Antidepressants may cause a variety of adverse effects; some side effects can increase the risk of falls. Before discontinuation, many antidepressants, such as the SSRIs, may need a taper to avoid a withdrawal syndrome. At least quarterly, the facility should review the continued need of the antidepressant and document the rationale for continuation. When the drug is being used to manage behavior, stabilize mood, or treat a psychiatric disorder, the facility should attempt to taper the medication as outlined in the OBRA guidelines, unless a taper is clinically contraindicated.[60742]

    ADVERSE REACTIONS

    Severe

    bradycardia / Rapid / 0.1-1.0
    myocardial infarction / Delayed / 0.1-1.0
    stroke / Early / 0.1-1.0
    heart failure / Delayed / 0.1-1.0
    seizures / Delayed / 0.3-0.3
    cholecystitis / Delayed / 0-0.1
    coagulopathy / Delayed / 0-0.1
    atrial fibrillation / Early / 0-0.1
    cardiac arrest / Early / 0-0.1
    keratitis / Delayed / 0-0.1
    bronchospasm / Rapid / 0-0.1
    oliguria / Early / 0-0.1
    suicidal ideation / Delayed / 1.0
    pancreatitis / Delayed / Incidence not known
    thrombosis / Delayed / Incidence not known
    GI bleeding / Delayed / Incidence not known
    pulmonary embolism / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    SIADH / Delayed / Incidence not known
    ventricular fibrillation / Early / Incidence not known
    torsade de pointes / Rapid / Incidence not known
    ventricular tachycardia / Early / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    ocular hypertension / Delayed / Incidence not known
    hepatic necrosis / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    rhabdomyolysis / Delayed / Incidence not known
    serotonin syndrome / Delayed / Incidence not known
    bone fractures / Delayed / Incidence not known
    persistent pulmonary hypertension of the newborn / Delayed / Incidence not known
    neonatal abstinence syndrome / Early / Incidence not known

    Moderate

    ejaculation dysfunction / Delayed / 6.1-6.1
    teeth grinding (bruxism) / Delayed / 0.1-1.0
    hemorrhoids / Delayed / 0.1-1.0
    gastritis / Delayed / 0.1-1.0
    esophagitis / Delayed / 0.1-1.0
    dysphagia / Delayed / 0.1-1.0
    stomatitis / Delayed / 0.1-1.0
    myoclonia / Delayed / 0.1-1.0
    dyskinesia / Delayed / 0.1-1.0
    neuropathic pain / Delayed / 0.1-1.0
    hypertonia / Delayed / 0.1-1.0
    ataxia / Delayed / 0.1-1.0
    psychosis / Early / 0.1-1.0
    hallucinations / Early / 0.1-1.0
    euphoria / Early / 0.1-1.0
    lymphadenopathy / Delayed / 0.1-1.0
    anemia / Delayed / 0.1-1.0
    leukopenia / Delayed / 0.1-1.0
    peripheral vasodilation / Rapid / 0.1-1.0
    peripheral edema / Delayed / 0.1-1.0
    hypertension / Early / 0.1-1.0
    angina / Early / 0.1-1.0
    atopic dermatitis / Delayed / 0.1-1.0
    psoriasis / Delayed / 0.1-1.0
    dyspnea / Early / 0.1-1.0
    conjunctivitis / Delayed / 0.1-1.0
    elevated hepatic enzymes / Delayed / 0.1-1.0
    galactorrhea / Delayed / 0.1-1.0
    vaginal bleeding / Delayed / 0.1-1.0
    urinary retention / Early / 0.1-1.0
    urinary incontinence / Early / 0.1-1.0
    dysuria / Early / 0.1-1.0
    hyperglycemia / Delayed / 0.1-1.0
    bone pain / Delayed / 0.1-1.0
    myasthenia / Delayed / 0.1-1.0
    QT prolongation / Rapid / 0-0.5
    mania / Early / 0.2-0.2
    cholelithiasis / Delayed / 0-0.1
    glossitis / Early / 0-0.1
    colitis / Delayed / 0-0.1
    hyperesthesia / Delayed / 0-0.1
    lymphocytosis / Delayed / 0-0.1
    lymphopenia / Delayed / 0-0.1
    bleeding / Early / 0-0.1
    bundle-branch block / Early / 0-0.1
    phlebitis / Rapid / 0-0.1
    pneumonitis / Delayed / 0-0.1
    photophobia / Early / 0-0.1
    cataracts / Delayed / 0-0.1
    jaundice / Delayed / 0-0.1
    hepatitis / Delayed / 0-0.1
    hyperbilirubinemia / Delayed / 0-0.1
    nephrolithiasis / Delayed / 0-0.1
    flank pain / Delayed / 0-0.1
    hematuria / Delayed / 0-0.1
    hypoglycemia / Early / 0-0.1
    hypokalemia / Delayed / 0-0.1
    goiter / Delayed / 0-0.1
    hypothyroidism / Delayed / 0-0.1
    dehydration / Delayed / 0-0.1
    osteoporosis / Delayed / 0-0.1
    migraine / Early / 1.0
    depression / Delayed / 1.0
    confusion / Early / 1.0
    amnesia / Delayed / 1.0
    sinus tachycardia / Rapid / 1.0
    orthostatic hypotension / Delayed / 1.0
    hypotension / Rapid / 1.0
    blurred vision / Early / 1.0
    akathisia / Delayed / Incidence not known
    dystonic reaction / Delayed / Incidence not known
    choreoathetosis / Delayed / Incidence not known
    impulse control symptoms / Delayed / Incidence not known
    hostility / Early / Incidence not known
    hematoma / Early / Incidence not known
    platelet dysfunction / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    hyponatremia / Delayed / Incidence not known
    chest pain (unspecified) / Early / Incidence not known
    hyperprolactinemia / Delayed / Incidence not known
    priapism / Early / Incidence not known
    osteopenia / Delayed / Incidence not known
    withdrawal / Early / Incidence not known
    growth inhibition / Delayed / Incidence not known

    Mild

    nausea / Early / 21.0-21.0
    xerostomia / Early / 20.0-20.0
    drowsiness / Early / 18.0-18.0
    insomnia / Early / 15.0-15.0
    hyperhidrosis / Delayed / 11.0-11.0
    diarrhea / Early / 8.0-8.0
    tremor / Early / 8.0-8.0
    dyspepsia / Early / 5.0-5.0
    fatigue / Early / 5.0-5.0
    rhinitis / Early / 5.0-5.0
    anorexia / Delayed / 4.0-4.0
    vomiting / Early / 4.0-4.0
    anxiety / Delayed / 4.0-4.0
    libido decrease / Delayed / 1.3-3.8
    abdominal pain / Early / 3.0-3.0
    agitation / Early / 3.0-3.0
    sinusitis / Delayed / 3.0-3.0
    dysmenorrhea / Delayed / 3.0-3.0
    fever / Early / 2.0-2.0
    yawning / Early / 2.0-2.0
    orgasm dysfunction / Delayed / 1.1-1.1
    gingivitis / Delayed / 0.1-1.0
    eructation / Early / 0.1-1.0
    hypoesthesia / Delayed / 0.1-1.0
    hyperkinesis / Delayed / 0.1-1.0
    vertigo / Early / 0.1-1.0
    paranoia / Early / 0.1-1.0
    libido increase / Delayed / 0.1-1.0
    emotional lability / Early / 0.1-1.0
    nightmares / Early / 0.1-1.0
    epistaxis / Delayed / 0.1-1.0
    purpura / Delayed / 0.1-1.0
    leukocytosis / Delayed / 0.1-1.0
    syncope / Early / 0.1-1.0
    acne vulgaris / Delayed / 0.1-1.0
    urticaria / Rapid / 0.1-1.0
    alopecia / Delayed / 0.1-1.0
    skin discoloration / Delayed / 0.1-1.0
    photosensitivity / Delayed / 0.1-1.0
    xerosis / Delayed / 0.1-1.0
    xerophthalmia / Early / 0.1-1.0
    tinnitus / Delayed / 0.1-1.0
    ocular pain / Early / 0.1-1.0
    mastalgia / Delayed / 0.1-1.0
    breast enlargement / Delayed / 0.1-1.0
    increased urinary frequency / Early / 0.1-1.0
    muscle cramps / Delayed / 0.1-1.0
    gastroesophageal reflux / Delayed / 0-0.1
    hiccups / Early / 0-0.1
    ptosis / Delayed / 0-0.1
    lethargy / Early / 0-0.1
    pruritus ani / Early / 0-0.1
    hypertrichosis / Delayed / 0-0.1
    laryngitis / Delayed / 0-0.1
    mydriasis / Early / 0-0.1
    diplopia / Early / 0-0.1
    lacrimation / Early / 0-0.1
    gynecomastia / Delayed / 0-0.1
    weight loss / Delayed / 1.0
    weight gain / Delayed / 1.0
    flatulence / Early / 1.0
    hypersalivation / Early / 1.0
    dizziness / Early / 2.0
    paresthesias / Delayed / 1.0
    rash / Early / 1.0
    flushing / Rapid / 1.0
    pruritus / Rapid / 1.0
    cough / Delayed / 1.0
    dysgeusia / Early / 1.0
    amenorrhea / Delayed / 1.0
    polyuria / Early / 1.0
    irritability / Delayed / Incidence not known
    ecchymosis / Delayed / Incidence not known
    asthenia / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abciximab: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving abciximab. Monitor closely for signs and symptoms of bleeding.
    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like codeine with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like dihydrocodeine with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. A cohort study in > 26,000 patients found that SSRI use alone increased the risk for serious GI bleed by 3.6-fold; when an SSRI was combined with aspirin the risk was increased by > 5-fold. The absolute risk of GI bleed from concomitant therapy with aspirin and a SSRI was low (20/2640 patients) in this cohort study and the clinician may determine that the combined use of these drugs is appropriate.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. A cohort study in > 26,000 patients found that SSRI use alone increased the risk for serious GI bleed by 3.6-fold; when an SSRI was combined with aspirin the risk was increased by > 5-fold. The absolute risk of GI bleed from concomitant therapy with aspirin and a SSRI was low (20/2640 patients) in this cohort study and the clinician may determine that the combined use of these drugs is appropriate.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Codeine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like codeine with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Dextromethorphan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Hydrocodone: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like hydrocodone with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Oxycodone: (Moderate) The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue the suspected drugs if serotonin syndrome is suspected and manage cliinically. There has been a case report of possible serotonin syndrome caused by the combination of oxycodone and selective serotonin reuptake inhbitors (SSRIs).
    Acetaminophen; Pentazocine: (Major) Because of the potential risk and severity of serotonin syndrome reactions, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as pentazocine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome occurs, discontinue the offending agent(s) and institute appropriate therapy.
    Acetaminophen; Propoxyphene: (Moderate) Citalopram impairs metabolism via the CYP2D6 pathway at therapeutic doses. This can result in increased concentrations of drugs metabolized via the same pathway, including some opiate agonists.
    Acetaminophen; Tramadol: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like tramadol with serotonergic drugs, such as citalopram. Several cases of serotonin syndrome have been reported after the administration of tramadol with an SSRI. Post-marketing reports implicate the concurrent use of SSRIs with tramadol in some cases of seizures. Lastly, citalopram is a weak inhibitor of CYP2D6. The analgesic activity of tramadol is due to the activity of both the parent drug and the O-desmethyltramadol metabolite (M1), and M1 formation is dependent on CYP2D6. Therefore, use of tramadol with a CYP2D6-inhibitor may alter tramadol efficacy. In addition, inhibition of CYP2D6 metabolism is expected to result in reduced metabolic clearance of tramadol. This in turn may increase the risk of tramadol-related adverse events including serotonin syndrome and seizures. If serotonin syndrome is suspected, citalopram and concurrent serotonergic agents should be discontinued.
    Acetazolamide: (Moderate) Caution is advisable during concurrent use of citalopram and acetazolamide as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with citalopram.
    Alfuzosin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), concurrent use of alfuzosin and citalopram should be avoided if possible. Based on electrophysiology studies performed by the manufacturer, alfuzosin has a slight effect to prolong the QT interval. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg. Citalopram causes dose-dependent QT interval prolongation. According to its manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Almotriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering almotriptan with citalopram. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and selective serotonin reuptake inhibitors (SSRIs). Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue citalopram and almotriptan and initiate symptomatic treatment if serotonin syndrome occurs.
    Alteplase: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with an SSRI.
    Amiloride: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Amiodarone: (Major) Citalopram causes dose-dependent QT interval prolongation. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. According to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. The manufacturer of amiodarone recommends avoiding coadministraton and a careful assessment of risks versus benefits if coadministration cannot be avoided.
    Amitriptyline: (Major) Citalopram causes dose-dependent QT interval prolongation and tricyclic antidepressants are associated with a possible risk of QT prolongation and torsade de pointes (TdP). According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. In addition, because of the potential risk and severity of serotonin syndrome, caution should be observed when administering citalopram with other drugs that have serotonergic properties such as tricyclic antidepressants. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Clinicians should also be alert for pharmacokinetic interactions between tricyclic antidepressants (TCAs) and SSRIs. Citalopram is a weak inhibitor of CYP2D6, the isoenzyme responsible for metabolism of many of the tricyclic antidepressants. Coadministration of citalopram and imipramine did not significantly affect the plasma concentrations of either drug. However, the concentration of desipramine, the primary metabolite of imipramine, was increased by 50%. The clinical significance of the elevation in desipramine concentration is unknown. However, symptoms of toxicity, including seizures, have been reported when drugs from these 2 classes were used together. A decreased dosage of the TCA or the avoidance of concomitant SSRI therapy should be considered.
    Amitriptyline; Chlordiazepoxide: (Major) Citalopram causes dose-dependent QT interval prolongation and tricyclic antidepressants are associated with a possible risk of QT prolongation and torsade de pointes (TdP). According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. In addition, because of the potential risk and severity of serotonin syndrome, caution should be observed when administering citalopram with other drugs that have serotonergic properties such as tricyclic antidepressants. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Clinicians should also be alert for pharmacokinetic interactions between tricyclic antidepressants (TCAs) and SSRIs. Citalopram is a weak inhibitor of CYP2D6, the isoenzyme responsible for metabolism of many of the tricyclic antidepressants. Coadministration of citalopram and imipramine did not significantly affect the plasma concentrations of either drug. However, the concentration of desipramine, the primary metabolite of imipramine, was increased by 50%. The clinical significance of the elevation in desipramine concentration is unknown. However, symptoms of toxicity, including seizures, have been reported when drugs from these 2 classes were used together. A decreased dosage of the TCA or the avoidance of concomitant SSRI therapy should be considered.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Amlodipine; Telmisartan: (Minor) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with telmisartan, a weak CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Concurrent use of citalopram and clarithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Administration of clarithromycin has resulted in prolongation of the QT interval and TdP. Citalopram also causes dose-dependent QT interval prolongation. (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with lansoprazole, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Concurrent use of citalopram and clarithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Administration of clarithromycin has resulted in prolongation of the QT interval and TdP. Citalopram also causes dose-dependent QT interval prolongation. (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with omeprazole, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Amphetamines: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and citalopram. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Amprenavir: (Major) CYP3A4 is involved in the metabolism of citalopram. Anti-retroviral protease inhibitors may increase plasma concentrations of citalopram through CYP3A4 inhibition. Because citalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease citalopram clearance.
    Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include citalopram. In addition, platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
    Antithrombin III: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like antithrombin III. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
    Apalutamide: (Moderate) Monitor for decreased efficacy of citalopram if coadministration with apalutamide is necessary. Citalopram is a CYP3A4 and CYP2C19 substrate. Apalutamide is a strong CYP3A4 and CYP2C19 inducer. Coadministration with another strong CYP3A4 inducer did not affect citalopram plasma concentrations, but increased clearance of citalopram with strong CYP3A4 inducers is possible.
    Apixaban: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like apixaban. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
    Apomorphine: (Major) Concurrent use of citalopram and apomorphine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Limited data indicate that QT prolongation is also possible with apomorphine administration; the change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines. In one study, a single mean dose of 5.2 mg (range 2 to 10 mg) prolonged the QT interval by about 3 msec. However, large increases (> 60 msecs from pre-dose) have occurred in two patients receiving 6 mg doses. Doses <= 6 mg SC are associated with minimal increases in QTc; doses > 6 mg SC do not provide additional clinical benefit and are not recommended.
    Aprepitant, Fosaprepitant: (Moderate) Use caution if citalopram and aprepitant, fosaprepitant are used concurrently and monitor for an increase in citalopram-related adverse effects for several days after administration of a multi-day aprepitant regimen. Citalopram is a CYP3A4 substrate in vitro. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of citalopram. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
    Ardeparin: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like low molecular weight heparins. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
    Aripiprazole: (Major) Because both citalopram and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), this combination should be used cautiously and with close monitoring. In addition, citalopram is a weak inhibitor of CYP2D6, and increased plasma concentrations of CYP2D6 substrates, such as aripiprazole, may occur. Decreased metabolism of aripiprazole may lead to clinically important adverse reactions. Because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adults receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP2D6 inhibitor. Aripiprazole dosage adjustments are not required when aripiprazole is added as adjunctive treatment to antidepressants for major depressive disorder provided that the manufacturer's dosing guidelines for this indication are followed.
    Armodafinil: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with armodafinil, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Arsenic Trioxide: (Major) Avoid coadministration of citalopram and arsenic trioxide. Discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Citalopram causes dose-dependent QT interval prolongation. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
    Artemether; Lumefantrine: (Major) Artemether; lumefantrine is an inhibitor of and citalopram is metabolized by the CYP2D6 isoenzyme; therefore, coadministration may lead to increased citalopram concentrations. Furthermore, although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Concomitant use of artemether; lumefantrine with drugs that may prolong the QT interval, such as citalopram, should be avoided. According to the manufacturer of citalopram, ECG monitoring is recommended in patients receiving concurrent drugs that prolong the QT interval.
    Asenapine: (Major) Concurrent use of asenapine and citalopram should be avoided if possible. Citalopram causes dose-dependent QT interval prolongation and asenapine is associated with a possible risk for QT prolongation and torsade de pointes (TdP). According to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. However, if concurrent therapy is considered essential, ECG monitoring is recommended. In addition, citalopram is a weak inhibitor of CYP2D6, and increased plasma concentrations of antipsychotics partially metabolized via CYP2D6, such as asenapine, may occur. Decreased metabolism of asenapine may lead to adverse reactions such as extrapyramidal symptoms; however, because asenapine is metabolized by multiple CYP pathways, a clinically significant interaction is less likely to occur.
    Aspirin, ASA: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like codeine with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like dihydrocodeine with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
    Aspirin, ASA; Carisoprodol: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like codeine with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
    Aspirin, ASA; Dipyridamole: (Moderate) Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding. (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
    Aspirin, ASA; Omeprazole: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with omeprazole, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Aspirin, ASA; Oxycodone: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. (Moderate) The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue the suspected drugs if serotonin syndrome is suspected and manage cliinically. There has been a case report of possible serotonin syndrome caused by the combination of oxycodone and selective serotonin reuptake inhbitors (SSRIs).
    Aspirin, ASA; Pravastatin: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
    Atazanavir: (Major) CYP3A4 is involved in the metabolism of citalopram. Anti-retroviral protease inhibitors may increase plasma concentrations of citalopram through CYP3A4 inhibition. Because citalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease citalopram clearance.
    Atazanavir; Cobicistat: (Major) CYP3A4 is involved in the metabolism of citalopram. Anti-retroviral protease inhibitors may increase plasma concentrations of citalopram through CYP3A4 inhibition. Because citalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease citalopram clearance. (Moderate) Close monitoring for antidepressant response and careful dose titrations of the antidepressant therapy is recommended during coadministration of selective serotonin reuptake inhibitors (SSRIs) and cobicistat. Concurrent use may result in elevated SSRI plasma concentrations. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. All SSRIs are substrates for the hepatic isoenzyme CYP2D6, while citalopram, escitalopram, and sertraline are also substrates for CYP3A4; cobicistat is an inhibitor of both CYP2D6 and CYP3A4.
    Atenolol; Chlorthalidone: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Atomoxetine: (Moderate) Atomoxetine is primarily a substrate for the cytochrome P450 2D6 isoenzyme. A dosage adjustment of atomoxetine may be needed in normal populations when atomoxetine is administered with inhibitors of the CYP2D6 enzyme, such as citalopram. Although citalopram is a weak inhibitor of 2D6, the potential for an interaction exists. In vitro studies suggest that coadministration of CYP inhibitors to poor metabolizers will not further increase the plasma concentrations of atomoxetine.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Severe) According to the manufacturer of citalopram, treatment initiation with citalopram is contraindicated in patients currently receiving intravenous (IV) methylene blue due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than citalopram (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving citalopram and requiring urgent treatment with IV methylene blue, citalopram should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits outweigh the risks. The patient should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Citalopram may be re-initiated 24 hours after the last dose of methylene blue. Results from an in vitro study indicate that methylene blue is a potent, reversible inhibitor of the monoamine oxidase type A enzyme (MAO-A). MAO-A is responsible for the metabolism of serotonin; therefore, concurrent use of an MAO-A inhibitor with a serotonergic agent may result in a clinically significant interaction. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent, in patients receiving SSRIs, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with IV methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. One case describes a patient receiving citalopram who experienced agitation, restlessness, pupil dilation with sluggish response to light, myoclonic movements of the lower limbs, and brisk reflexes following an infusion of methylene blue, while another patient receiving paroxetine developed tachycardia, agitation, dystonia and abnormal eye movements. During a retrospective study of 193 surgical patients who had received a methylene blue injection, it was found that all 12 of the patients who experienced postoperative neurological sequelae had been taking a serotonin reuptake inhibitor preoperatively. One of the 12 patients experienced cardiopulmonary arrest and died. Of the remaining 181 patients who did not experience neurological sequelae, 8.8% were taking a serotonin reuptake inhibitor. Published interaction reports between IV methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and coma. Signs and symptoms of serotonin syndrome include fever, diaphoresis, shivering, myoclonus, tremor, tachycardia, diarrhea, nausea, headache, incoordination, mental status changes (e.g., agitation, confusion), hyperreflexia, seizures, and coma. (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin.
    Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with citalopram can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Atropine; Diphenoxylate: (Moderate) Concurrent administration of diphenoxylate/difenoxin with citalopram can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Azelastine; Fluticasone: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Azilsartan; Chlorthalidone: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Azithromycin: (Major) Concurrent use of citalopram with azithromycin is not recommended due to an increased risk for QT prolongation and torsade de pointes (TdP). Citalopram causes dose-dependent QT interval prolongation, and azithromycin has been associated with cases of QT prolongation and TdP. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Barbiturates: (Moderate) Citalopram is metabolized by CYP2C19 and CYP3A4. Barbiturates can induce the metabolism of various CYP 450 isoenzymes, including those involved in citalopram metabolism. Although no clinical data are available to support a clinically significant interaction, citalopram may need to be administered in higher doses in patients chronically taking barbiturates.
    Beclomethasone: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Bedaquiline: (Major) Concurrent use of citalopram and bedaquiline should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Bedaquiline has been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy. Citalopram also causes dose-dependent QT interval prolongation.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been co-administered with SSRI's (e.g., citalopram), which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
    Belladonna; Opium: (Moderate) Citalopram impairs metabolism via the CYP2D6 pathway at therapeutic doses. This can result in increased concentrations of drugs metabolized via the same pathway, including some opiate agonists.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Bendroflumethiazide; Nadolol: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Benzhydrocodone; Acetaminophen: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of benzhydrocodone and citalopram because of the potential risk of serotonin syndrome. Discontinue benzhydrocodone if serotonin syndrome is suspected. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Severe) According to the manufacturer of citalopram, treatment initiation with citalopram is contraindicated in patients currently receiving intravenous (IV) methylene blue due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than citalopram (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving citalopram and requiring urgent treatment with IV methylene blue, citalopram should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits outweigh the risks. The patient should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Citalopram may be re-initiated 24 hours after the last dose of methylene blue. Results from an in vitro study indicate that methylene blue is a potent, reversible inhibitor of the monoamine oxidase type A enzyme (MAO-A). MAO-A is responsible for the metabolism of serotonin; therefore, concurrent use of an MAO-A inhibitor with a serotonergic agent may result in a clinically significant interaction. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent, in patients receiving SSRIs, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with IV methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. One case describes a patient receiving citalopram who experienced agitation, restlessness, pupil dilation with sluggish response to light, myoclonic movements of the lower limbs, and brisk reflexes following an infusion of methylene blue, while another patient receiving paroxetine developed tachycardia, agitation, dystonia and abnormal eye movements. During a retrospective study of 193 surgical patients who had received a methylene blue injection, it was found that all 12 of the patients who experienced postoperative neurological sequelae had been taking a serotonin reuptake inhibitor preoperatively. One of the 12 patients experienced cardiopulmonary arrest and died. Of the remaining 181 patients who did not experience neurological sequelae, 8.8% were taking a serotonin reuptake inhibitor. Published interaction reports between IV methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and coma. Signs and symptoms of serotonin syndrome include fever, diaphoresis, shivering, myoclonus, tremor, tachycardia, diarrhea, nausea, headache, incoordination, mental status changes (e.g., agitation, confusion), hyperreflexia, seizures, and coma. (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin.
    Betamethasone: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Betrixaban: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like betrixaban. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include citalopram.
    Bismuth Subsalicylate: (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include citalopram. (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering citalopram with boceprevir due to an increased potential for citalopram-related adverse events. If citalopram dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of citalopram. Citalopram is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated citalopram plasma concentrations.
    Brimonidine; Timolol: (Minor) Citalopram mildly inhibits the hepatic CYP2D6 isoenzyme at therapeutic doses. This can result in increased concentrations of drugs metabolized via the same pathway, including timolol.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like hydrocodone with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like hydrocodone with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Budesonide: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Budesonide; Formoterol: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Bumetanide: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Bupivacaine; Lidocaine: (Moderate) Concomitant use of systemic lidocaine and citalopram may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; citalopram is a weak CYP1A2 inhibitor.
    Buprenorphine: (Major) Due to the potential for QT prolongation, coadministration of citalopram and buprenorphine should be avoided. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Citalopram causes dose-dependent QT interval prolongation. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If concurrent therapy is considered essential, ECG monitoring is recommended. In addition, concurrent use of opioids with other drugs that modulate serotonergic function, such as SSRIs, has resulted in serotonin syndrome in some cases. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If combination treatment is required, patients should be carefully observed, particularly during treatment initiation and during dose adjustments of the serotonergic drug; discontinue buprenorphine if serotonin syndrome is suspected.
    Buprenorphine; Naloxone: (Major) Due to the potential for QT prolongation, coadministration of citalopram and buprenorphine should be avoided. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Citalopram causes dose-dependent QT interval prolongation. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If concurrent therapy is considered essential, ECG monitoring is recommended. In addition, concurrent use of opioids with other drugs that modulate serotonergic function, such as SSRIs, has resulted in serotonin syndrome in some cases. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If combination treatment is required, patients should be carefully observed, particularly during treatment initiation and during dose adjustments of the serotonergic drug; discontinue buprenorphine if serotonin syndrome is suspected.
    Bupropion: (Moderate) A pharmacokinetic interaction has been observed between bupropion and citalopram. In one study, bupropion increased the Cmax and AUC of citalopram by 30% and 40%, respectively. Citalopram did not affect the kinetics of bupropion or its metabolites. The mechanism of this interaction has not been clearly established since citalopram is primarily metabolized by the isoenzymes CYP3A4 and CYP2C19 and bupropion and its metabolite hydroxybupropion are metabolized by CYP2B6 and are inhibitors of CYP2D6.
    Bupropion; Naltrexone: (Moderate) A pharmacokinetic interaction has been observed between bupropion and citalopram. In one study, bupropion increased the Cmax and AUC of citalopram by 30% and 40%, respectively. Citalopram did not affect the kinetics of bupropion or its metabolites. The mechanism of this interaction has not been clearly established since citalopram is primarily metabolized by the isoenzymes CYP3A4 and CYP2C19 and bupropion and its metabolite hydroxybupropion are metabolized by CYP2B6 and are inhibitors of CYP2D6.
    Buspirone: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as buspirone and citalopram. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Cabergoline: (Moderate) Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as cabergoline. Patients receiving cabergoline with an SSRI should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
    Caffeine; Ergotamine: (Moderate) Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been co-administered with SSRI's (e.g., citalopram), which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Cangrelor: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymosis, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cangrelor). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Carbamazepine: (Moderate) Carbamazepine may potentially accelerate the hepatic metabolism of citalopram. Clinicians should be alert to altered effects of citalopram. Dosage adjustments may be necessary.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like hydrocodone with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like hydrocodone with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Carvedilol: (Minor) Citalopram mildly inhibits the hepatic CYP2D6 isoenzyme at therapeutic doses. This can result in increased concentrations of drugs metabolized via the same pathway, including carvedilol.
    Ceritinib: (Major) Coadministration of citalopram with ceritinib is not recommended due to the risk of QT prolongation; citalopram exposure may also be increased. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Citalopram is a CYP3A4 substrate that causes dose-dependent QT prolongation. Ceritinib is a strong CYP3A4 inhibitor that is also associated with concentration-dependent QT prolongation.
    Cevimeline: (Moderate) Cevimeline is metabolized by cytochrome P450 3A4 and CYP2D6. Inhibitors of either of these isoenzymes, such as the SSRIs, would be expected to lead to an increase in cevimeline plasma concentrations.
    Chloramphenicol: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with chloramphenicol, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Chloroquine: (Major) According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval, such as chloroquine, is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); fatalities have been reported. The risk of QT prolongation is increased with higher chloroquine doses.
    Chlorothiazide: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Chlorpheniramine; Codeine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like codeine with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Chlorpheniramine; Dextromethorphan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like dihydrocodeine with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like dihydrocodeine with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like hydrocodone with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Chlorpheniramine; Hydrocodone: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like hydrocodone with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like hydrocodone with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like hydrocodone with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Chlorpromazine: (Major) Concurrent use of citalopram and chlorpromazine should be avoided. Citalopram causes dose-dependent QT interval prolongation and chlorpromazine is associated with an established risk of QT prolongation and torsade de pointes (TdP). According to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with drugs that are dopamine antagonists such as phenothiazines. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Citalopram is a weak inhibitor of the CYP2D6 pathway and may result in increases in serum phenothiazine concentrations, leading to side effects. Patients receiving a phenothiazine and an SSRI should be monitored for the emergence of serotonin syndrome, neuroleptic malignant syndrome-like reactions, or other adverse effects.
    Chlorthalidone: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Chlorthalidone; Clonidine: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Choline Salicylate; Magnesium Salicylate: (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. A cohort study in > 26,000 patients found that SSRI use alone increased the risk for serious GI bleed by 3.6-fold; when an SSRI was combined with aspirin the risk was increased by > 5-fold. The absolute risk of GI bleed from concomitant therapy with aspirin and a SSRI was low (20/2640 patients) in this cohort study and the clinician may determine that the combined use of these drugs is appropriate.
    Ciclesonide: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Cilostazol: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding.
    Cimetidine: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with cimetidine, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors. In clinical trial subjects, combined administration of cimetidine and citalopram for 8 days resulted in an increase in citalopram AUC and Cmax of 43% and 39%, respectively.
    Ciprofloxacin: (Major) Concurrent use of citalopram and ciprofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Ciprofloxacin is associated with a possible risk for QT prolongation and TdP.
    Cisapride: (Severe) QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Because of the potential for TdP, use of cisapride with citalopram is contraindicated.
    Clarithromycin: (Major) Concurrent use of citalopram and clarithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Administration of clarithromycin has resulted in prolongation of the QT interval and TdP. Citalopram also causes dose-dependent QT interval prolongation.
    Clofazimine: (Major) Avoid coadministration of clofazimine and citalopram due to the potential for additive QT prolongation. Monitor ECG for QT prolongation if coadministration is required. QT prolongation and torsade de pointes have been reported in patients receiving clofazimine in combination with QT prolonging medications. Citalopram causes dose-dependent QT interval prolongation.
    Clomipramine: (Major) Citalopram causes dose-dependent QT interval prolongation and tricyclic antidepressants are associated with a possible risk of QT prolongation and torsade de pointes (TdP). According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. In addition, because of the potential risk and severity of serotonin syndrome, caution should be observed when administering citalopram with other drugs that have serotonergic properties such as tricyclic antidepressants. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Clinicians should also be alert for pharmacokinetic interactions between tricyclic antidepressants (TCAs) and SSRIs. Citalopram is a weak inhibitor of CYP2D6, the isoenzyme responsible for metabolism of many of the tricyclic antidepressants. Coadministration of citalopram and imipramine did not significantly affect the plasma concentrations of either drug. However, the concentration of desipramine, the primary metabolite of imipramine, was increased by 50%. The clinical significance of the elevation in desipramine concentration is unknown. However, symptoms of toxicity, including seizures, have been reported when drugs from these 2 classes were used together. A decreased dosage of the TCA or the avoidance of concomitant SSRI therapy should be considered.
    Clopidogrel: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of citalopram and clopidogrel. Selective serotonin reuptake inhibitors (SSRIs) affect platelet activation; therefore, concomitant use may increase the risk of bleeding.
    Clozapine: (Major) Concurrent use of clozapine and citalopram should be avoided if possible. Citalopram causes dose-dependent QT interval prolongation and clozapine is associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. According to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. However, if concurrent therapy is considered essential, ECG monitoring is recommended. In addition, citalopram is a weak inhibitor of CYP2D6, and increased plasma concentrations of antipsychotics partially metabolized via CYP2D6, such as clozapine, may occur. A reduced dosage of clozapine should be considered when clozapine is combined with CYP2D6 inhibitors, due to a decrease in clozapine metabolism and a potential for clozapine-related adverse effects, such as orthostatic hypotension, seizures, or adverse cardiac effects.
    Cobicistat: (Moderate) Close monitoring for antidepressant response and careful dose titrations of the antidepressant therapy is recommended during coadministration of selective serotonin reuptake inhibitors (SSRIs) and cobicistat. Concurrent use may result in elevated SSRI plasma concentrations. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. All SSRIs are substrates for the hepatic isoenzyme CYP2D6, while citalopram, escitalopram, and sertraline are also substrates for CYP3A4; cobicistat is an inhibitor of both CYP2D6 and CYP3A4.
    Cocaine: (Major) Concomitant use of cocaine with drugs that have CNS serotonergic properties, such as SSRIs, could potentiate serotonin neurotransmission, and result in the serotonin syndrome. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions. Additionally, citalopram causes dose-dependent QT interval prolongation. Local anesthetics (e.g., cocaine) are associated with a possible risk for QT prolongation and according to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Codeine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like codeine with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Codeine; Guaifenesin: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like codeine with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Codeine; Phenylephrine; Promethazine: (Major) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Promethazine carries a possible risk of QT prolongation. (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like codeine with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Codeine; Promethazine: (Major) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Promethazine carries a possible risk of QT prolongation. (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like codeine with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Corticosteroids: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Corticotropin, ACTH: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Cortisone: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Crizotinib: (Major) Coadministration of crizotinib with citalopram is not recommended due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs. Both drugs have been associated with concentration-dependent QT prolongation.
    Cyproheptadine: (Moderate) Cyproheptadine is a serotonin antagonist in the CNS and can oppose the pharmacologic actions of selective serotonin reuptake inhibitors (SSRIs) such as citalopram. Cyproheptadine has been used for the management of orgasm dysfunction caused by the SSRIs and for the adjunctive treatment of SSRI overdose (i.e., serotonin syndrome) in emergency situations; however, a reversal of antidepressant effects may occur when cyproheptadine is given in a routine manner along with the SSRIs due to the serotonin antagonistic effects of cyproheptadine.
    Dabigatran: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like dabigatran. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
    Dalteparin: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like low molecular weight heparins. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
    Danaparoid: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like danaparoid. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
    Darifenacin: (Moderate) Clinicians should monitor patients for increased anticholinergic effects when darifenacin, a CYP2D6 substrate, is coadministered with citalopram, a mild CYP2D6 inhibitor; the dosage of darifenacin may need to be adjusted.
    Darunavir: (Major) CYP3A4 is involved in the metabolism of citalpram. Anti-retroviral protease inhibitors may increase plasma concentrations of citalopram through CYP3A4 inhibition. Because citalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease citalopram clearance.
    Darunavir; Cobicistat: (Major) CYP3A4 is involved in the metabolism of citalpram. Anti-retroviral protease inhibitors may increase plasma concentrations of citalopram through CYP3A4 inhibition. Because citalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease citalopram clearance. (Moderate) Close monitoring for antidepressant response and careful dose titrations of the antidepressant therapy is recommended during coadministration of selective serotonin reuptake inhibitors (SSRIs) and cobicistat. Concurrent use may result in elevated SSRI plasma concentrations. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. All SSRIs are substrates for the hepatic isoenzyme CYP2D6, while citalopram, escitalopram, and sertraline are also substrates for CYP3A4; cobicistat is an inhibitor of both CYP2D6 and CYP3A4.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) CYP3A4 is involved in the metabolism of citalpram. Anti-retroviral protease inhibitors may increase plasma concentrations of citalopram through CYP3A4 inhibition. Because citalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease citalopram clearance. (Moderate) Close monitoring for antidepressant response and careful dose titrations of the antidepressant therapy is recommended during coadministration of selective serotonin reuptake inhibitors (SSRIs) and cobicistat. Concurrent use may result in elevated SSRI plasma concentrations. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. All SSRIs are substrates for the hepatic isoenzyme CYP2D6, while citalopram, escitalopram, and sertraline are also substrates for CYP3A4; cobicistat is an inhibitor of both CYP2D6 and CYP3A4.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Minor) Concurrent use of ritonavir may increase citalopram exposure and treatment-related adverse effects. Ritonavir is a strong CYP3A4 inhibitor. Because CYP3A4 is one of the primary enzymes involved in the metabolism of citalopram, it is expected that strong CYP3A4 inhibitors might decrease the clearance of citalopram. However, coadministration of citalopram and another strong CYP3A4 inhibitor ketoconazole did not significantly affect the pharmacokinetics of citalopram.
    Dasatinib: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), concurrent use of dasatinib and citalopram should be avoided if possible. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Deflazacort: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Degarelix: (Major) Citalopram causes dose-dependent QT interval prolongation. Degarelix is associated with a possible risk for QT prolongation and TdP (torsade de pointes). According to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Delavirdine: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with delavirdine, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Desflurane: (Major) Halogenated anesthetics are associated with a risk for QT prolongation. Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Desipramine: (Major) Citalopram causes dose-dependent QT interval prolongation and tricyclic antidepressants are associated with a possible risk of QT prolongation and torsade de pointes (TdP). According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. In addition, because of the potential risk and severity of serotonin syndrome, caution should be observed when administering citalopram with other drugs that have serotonergic properties such as tricyclic antidepressants. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Clinicians should also be alert for pharmacokinetic interactions between tricyclic antidepressants (TCAs) and SSRIs. Citalopram is a weak inhibitor of CYP2D6, the isoenzyme responsible for metabolism of many of the tricyclic antidepressants. Coadministration of citalopram and imipramine did not significantly affect the plasma concentrations of either drug. However, the concentration of desipramine, the primary metabolite of imipramine, was increased by 50%. The clinical significance of the elevation in desipramine concentration is unknown. However, symptoms of toxicity, including seizures, have been reported when drugs from these 2 classes were used together. A decreased dosage of the TCA or the avoidance of concomitant SSRI therapy should be considered.
    Desmopressin: (Minor) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with water intoxication, hyponatremia, or SIADH including SSRIs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia, which may include monitoring serum sodium or electrolytes periodically. Ensure the patient is compliant with fluid restrictions and intake.
    Desvenlafaxine: (Major) Due to similarity of pharmacology and the potential for additive adverse effects, including serotonin syndrome, selective serotonin reuptake inhibitors (SSRIs) should generally not be administered with serotonin norepinephrine reuptake inhibitors like desvenlafaxine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Discontinuation symptoms have been reported when switching from other antidepressants to desvenlafaxine. It may be advisable to taper the previous antidepressant to minimize discontinuation symptoms.
    Deutetrabenazine: (Major) Concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. For patients taking a deutetrabenazine dosage more than 24 mg/day with citalopram, assess the QTc interval before and after increasing the dosage of either medication. Clinically relevant QTc prolongation may occur with deutetrabenazine. Citalopram causes dose-dependent QT interval prolongation.
    Dexamethasone: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Dexmethylphenidate: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as dexmethylphenidate and selective serotonin reuptake inhibitors (SSRIs). There are rare reports of serotonin syndrome occurring during use of an SSRI and methylphenidate, a racemic compound containing dexmethylphenidate. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
    Dextromethorphan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Dextromethorphan; Guaifenesin: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Dextromethorphan; Promethazine: (Major) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Promethazine carries a possible risk of QT prolongation. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Dextromethorphan; Quinidine: (Major) Because citalopram and quinidine are associated with QT prolongation, these combinations should be used cautiously and with close monitoring. The manufacturers of quinidine and citalopram recommend an ECG in patients taking either of these drugs in combination with other drugs known to cause QT prolongation. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Diazepam: (Moderate) Clinicians should use citalopram cautiously with diazepam since co-administration with citalopram could potentially result in additive pharmacodynamic effects within the CNS.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like dihydrocodeine with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Dihydroergotamine: (Moderate) Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been co-administered with SSRI's (e.g., citalopram), which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
    Diltiazem: (Moderate) During concurrent use of citalopram and diltiazem, clinicians should monitor patients for a potential increase in side effects or toxicity. In theory, diltiazem may inhibit the metabolism of citalopram through inhibition of CYP3A4. It should be noted that because citalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease citalopram clearance.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like hydrocodone with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Dipyridamole: (Moderate) Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding.
    Disopyramide: (Major) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with citalopram include disopyramide, Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP).
    Diuretics: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Dofetilide: (Major) Coadministration of dofetilide and citalopram is not recommended as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Citalopram causes dose-dependent QT interval prolongation.
    Dolasetron: (Major) Coadministration of citalopram and dolasetron is not recommended due to the potential risk of QT prolongation. If concurrent therapy is considered essential, ECG monitoring is recommended. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Citalopram causes dose-dependent QT interval prolongation. Concurrent use may increase the risk of QT prolongation.
    Dolutegravir; Rilpivirine: (Major) Concurrent use of citalopram and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Citalopram also causes dose-dependent QT interval prolongation.
    Donepezil: (Major) Due to the risk of QT prolongation, citalopram should be avoided in combination with donepezil, if possible. Consider if an alternative to citalopram would be appropriate in dementia patients taking donepezil. If concurrent therapy is considered essential, ECG monitoring is recommended, and do not exceed recommended doses. Citalopram causes dose-dependent QT interval prolongation. Monitor ECG if concurrent use cannot be avoided, and monitor for changes in moods and behaviors. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy. Citalopram has been studied in patients with Alzheimer's disease and clinically significant agitation; patients were receiving donepezil. While citalopram significantly reduced agitation and caregiver distress vs. placebo, the use of citalopram was associated with QTc prolongation and cognitive worsening.
    Donepezil; Memantine: (Major) Due to the risk of QT prolongation, citalopram should be avoided in combination with donepezil, if possible. Consider if an alternative to citalopram would be appropriate in dementia patients taking donepezil. If concurrent therapy is considered essential, ECG monitoring is recommended, and do not exceed recommended doses. Citalopram causes dose-dependent QT interval prolongation. Monitor ECG if concurrent use cannot be avoided, and monitor for changes in moods and behaviors. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy. Citalopram has been studied in patients with Alzheimer's disease and clinically significant agitation; patients were receiving donepezil. While citalopram significantly reduced agitation and caregiver distress vs. placebo, the use of citalopram was associated with QTc prolongation and cognitive worsening.
    Dorzolamide; Timolol: (Minor) Citalopram mildly inhibits the hepatic CYP2D6 isoenzyme at therapeutic doses. This can result in increased concentrations of drugs metabolized via the same pathway, including timolol.
    Doxepin: (Major) Citalopram causes dose-dependent QT interval prolongation and tricyclic antidepressants are associated with a possible risk of QT prolongation and torsade de pointes (TdP). According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. In addition, because of the potential risk and severity of serotonin syndrome, caution should be observed when administering citalopram with other drugs that have serotonergic properties such as tricyclic antidepressants. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Clinicians should also be alert for pharmacokinetic interactions between tricyclic antidepressants (TCAs) and SSRIs. Citalopram is a weak inhibitor of CYP2D6, the isoenzyme responsible for metabolism of many of the tricyclic antidepressants. Coadministration of citalopram and imipramine did not significantly affect the plasma concentrations of either drug. However, the concentration of desipramine, the primary metabolite of imipramine, was increased by 50%. The clinical significance of the elevation in desipramine concentration is unknown. However, symptoms of toxicity, including seizures, have been reported when drugs from these 2 classes were used together. A decreased dosage of the TCA or the avoidance of concomitant SSRI therapy should be considered.
    Doxercalciferol: (Moderate) Doxercalciferol is converted in the liver to 1,25-dihydroxyergocalciferol, the major active metabolite, and 1-alpha, 24-dihydroxyvitamin D2, a minor metabolite. Although not specifically studied, cytochrome P450 enzyme inhibitors, including selective serotonin reuptake inhibitors (SSRIs), may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if SSRIs are coadministered with doxercalciferol.
    Dronedarone: (Severe) Concurrent use of citalopram and dronedarone is contraindicated. Citalopram causes dose-dependent QT interval prolongation. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
    Droperidol: (Major) Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). Any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with droperidol include citalopram. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Duloxetine: (Major) Due to similarity of pharmacology and the potential for additive adverse effects, including serotonin syndrome, selective serotonin reuptake inhibitors (SSRIs) should generally not be administered with serotonin norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine, desvenlafaxine, duloxetine, and milnacipran. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Dutasteride; Tamsulosin: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as citalopram. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Edoxaban: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like edoxaban. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
    Efavirenz: (Major) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. QT prolongation has been observed with use of efavirenz. If concurrent therapy is considered essential, ECG monitoring is recommended. In addition, because citalopram is a substrate for CYP2C19, the maximum daily dose of citalopram should not exceed 20 mg/day in patients receiving CYP2C19 inhibitors such as efavirenz. During concurrent use of citalopram and efavirenz, clinicians should monitor patients for a potential increase in side effects or toxicity.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. QT prolongation has been observed with use of efavirenz. If concurrent therapy is considered essential, ECG monitoring is recommended. In addition, because citalopram is a substrate for CYP2C19, the maximum daily dose of citalopram should not exceed 20 mg/day in patients receiving CYP2C19 inhibitors such as efavirenz. During concurrent use of citalopram and efavirenz, clinicians should monitor patients for a potential increase in side effects or toxicity.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. QT prolongation has been observed with use of efavirenz. If concurrent therapy is considered essential, ECG monitoring is recommended. In addition, because citalopram is a substrate for CYP2C19, the maximum daily dose of citalopram should not exceed 20 mg/day in patients receiving CYP2C19 inhibitors such as efavirenz. During concurrent use of citalopram and efavirenz, clinicians should monitor patients for a potential increase in side effects or toxicity.
    Elagolix: (Moderate) CItalopram 20 mg/day is the maximum recommended dose for patients taking concomitant CYP2C19 inhibitors because of the risk of QT prolongation. Elagolix is a weak CYP2C19 inhibitor and a weak to moderate CYP3A4 inducer and citalopram is a CYP2C19 and CYP3A4 substrate. The net effect of elagolix on citalopram exposure is not clear.
    Elbasvir; Grazoprevir: (Moderate) Administering citalopram with elbasvir; grazoprevir may result in elevated citalopram plasma concentrations. Citalopram is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
    Eletriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering eletriptan with citalopram. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and selective serotonin reuptake inhibitors (SSRIs). Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue citalopram and eletriptan and initiate symptomatic treatment if serotonin syndrome occurs.
    Eliglustat: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include citalopram.
    Eltrombopag: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inhibitors of CYP1A2, such as citalopram, on the systemic exposure of eltrombopag has not been established. Monitor patients for signs of eltrombopag toxicity if these drugs are coadministered.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Close monitoring for antidepressant response and careful dose titrations of the antidepressant therapy is recommended during coadministration of selective serotonin reuptake inhibitors (SSRIs) and cobicistat. Concurrent use may result in elevated SSRI plasma concentrations. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. All SSRIs are substrates for the hepatic isoenzyme CYP2D6, while citalopram, escitalopram, and sertraline are also substrates for CYP3A4; cobicistat is an inhibitor of both CYP2D6 and CYP3A4.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Close monitoring for antidepressant response and careful dose titrations of the antidepressant therapy is recommended during coadministration of selective serotonin reuptake inhibitors (SSRIs) and cobicistat. Concurrent use may result in elevated SSRI plasma concentrations. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. All SSRIs are substrates for the hepatic isoenzyme CYP2D6, while citalopram, escitalopram, and sertraline are also substrates for CYP3A4; cobicistat is an inhibitor of both CYP2D6 and CYP3A4.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Concurrent use of citalopram and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Citalopram also causes dose-dependent QT interval prolongation.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Concurrent use of citalopram and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Citalopram also causes dose-dependent QT interval prolongation.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Encainide: (Moderate) Citalopram mildly inhibits the hepatic CYP2D6 isoenzyme at therapeutic doses. This can result in increased concentrations of drugs metabolized via the same pathway, including some encainide.
    Encorafenib: (Major) Concurrent use of citalopram with encorafenib is not recommended due to QT prolongation. If concurrent therapy is considered essential, ECG monitoring is recommended. Monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Citalopram causes dose-dependent QT interval prolongation.
    Enflurane: (Major) Halogenated anesthetics are associated with a risk for QT prolongation. Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Enoxaparin: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like low molecular weight heparins. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
    Entrectinib: (Major) Avoid coadministration of entrectinib with citalopram due to the risk of QT prolongation. If concurrent therapy is considered essential, ECG monitoring is recommended. Entrectinib has been associated with QT prolongation. Citalopram causes dose-dependent QT interval prolongation.
    Enzalutamide: (Moderate) Monitor for decreased efficacy of citalopram if coadministration with enzalutamide is necessary. Citalopram is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer did not affect citalopram plasma concentrations, but increased clearance of citalopram with strong CYP3A4 inducers is possible.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Eptifibatide: (Moderate) Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding.
    Ergoloid Mesylates: (Moderate) Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been co-administered with SSRI's (e.g., citalopram), which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
    Ergonovine: (Moderate) Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been co-administered with SSRI's (e.g., citalopram), which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
    Ergot alkaloids: (Moderate) Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been co-administered with SSRI's (e.g., citalopram), which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
    Ergotamine: (Moderate) Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been co-administered with SSRI's (e.g., citalopram), which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
    Eribulin: (Major) Citalopram causes dose-dependent QT interval prolongation. Eribulin is associated with a possible risk for QT prolongation and TdP (torsade de pointes). According to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Erythromycin: (Major) Concurrent use of citalopram and erythromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Erythromycin is also associated with prolongation of the QT interval and TdP.
    Erythromycin; Sulfisoxazole: (Major) Concurrent use of citalopram and erythromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Erythromycin is also associated with prolongation of the QT interval and TdP.
    Escitalopram: (Severe) Due to the similarity in pharmacology of citalopram and escitalopram and the potential for serious adverse reactions, including serotonin syndrome, these selective serotonin reuptake inhibitors (SSRIs) should not be administered together. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Also, both citalopram and escitalopram have been associated with QT prolongation and torsade de pointes (TdP), which could theoretically result in additive effects on the QT interval. It is advisable to monitor for signs and symptoms of serotonin syndrome during an overlapping transition from one SSRI to another SSRI.
    Eslicarbazepine: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with eslicarbazepine, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Esomeprazole: (Moderate) Esomeprazole, a CYP2C19 inhibitor, may iincrease concentrations of citalopram, which may increase the risk for QT prolongation or serotonin side effects.The maximum daily dose of citalopram should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors. Monitor the patient for serotonin excess or symptoms of other citalopram-related side effects. In one study, citalopram concentrations were significantly higher in patients treated with esomeprazole (increased 32.8%).
    Esomeprazole; Naproxen: (Moderate) Esomeprazole, a CYP2C19 inhibitor, may iincrease concentrations of citalopram, which may increase the risk for QT prolongation or serotonin side effects.The maximum daily dose of citalopram should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors. Monitor the patient for serotonin excess or symptoms of other citalopram-related side effects. In one study, citalopram concentrations were significantly higher in patients treated with esomeprazole (increased 32.8%).
    Ethacrynic Acid: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Ethanol: (Moderate) Although citalopram has not been shown to increase mental and motor skill impairments related to alcohol consumption, the combination of citalopram and alcohol in depressed patients is not advised.
    Etravirine: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with etravirine, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Ezogabine: (Major) Citalopram causes dose-dependent QT interval prolongation. Ezogabine is associated with a possible risk for QT prolongation and TdP (torsade de pointes). According to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Fedratinib: (Major) Because citalopram causes dose-dependent QT prolongation, the maximum daily dose of citalopram should not exceed 20 mg per day in patients receiving fedratinib. The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with fedratinib, a moderate CYP2C19 inhibitor.
    Felbamate: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with felbamate, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Fenofibric Acid: (Minor) At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as citalopram, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. The manufacturer of citalopram recommends 20 mg/day as the maximum daily dose of citalopram in patients receiving CYP2C19 inhibitors, due to the potential risk for QT prolongation. Monitor the therapeutic effect of citalopram during coadministration with fenofibric acid.
    Fentanyl: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like fentanyl with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Fingolimod: (Major) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. If coadministration is necessary, after the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of torsades de pointes (TdP). Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with fingolimod include citalopram.
    Flecainide: (Major) Concurrent use of flecainide and citalopram should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Flecainide, a Class IC antiarrhythmic, is also associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. In addition, flecainide is significantly metabolized by CYP2D6 isoenzymes and citalopram is a weak inhibitor of CYP2D6. Coadministation may increase the serum concentrations of flecainide.
    Fluconazole: (Severe) Due to the risk of life-threatening arrhythmias such as torsade de pointes (TdP), coadministration of fluconazole with drugs that both prolong the QT interval and are CYP3A4 substrates, such as citalopram, is contraindicated. Fluconazole has been associated with QT prolongation and rare cases of TdP. Additonally, fluconazole is an inhibitor of CYP3A4. Coadministration may result in elevated plasma concentrations of citalopram, causing an increased risk for adverse events such as QT prolongation.
    Fludrocortisone: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Flunisolide: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Fluoxetine: (Severe) Due to the similarity in pharmacology of fluoxetine and citalopram and the potential for serious adverse reactions, including serotonin syndrome, these selective serotonin reuptake inhibitors (SSRIs) should not be administered together. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Also, both fluoxetine and citalopram have been associated with QT prolongation and torsade de pointes (TdP), which could theoretically result in additive effects on the QT interval. It is advisable to monitor for signs and symptoms of serotonin syndrome during an overlapping transition from one SSRI to another SSRI.
    Fluoxetine; Olanzapine: (Severe) Due to the similarity in pharmacology of fluoxetine and citalopram and the potential for serious adverse reactions, including serotonin syndrome, these selective serotonin reuptake inhibitors (SSRIs) should not be administered together. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Also, both fluoxetine and citalopram have been associated with QT prolongation and torsade de pointes (TdP), which could theoretically result in additive effects on the QT interval. It is advisable to monitor for signs and symptoms of serotonin syndrome during an overlapping transition from one SSRI to another SSRI. (Major) Concurrent use of olanzapine and citalopram should be avoided if possible. Citalopram causes dose-dependent QT interval prolongation and olanzapine is associated with a risk for QT prolongation and torsade de pointes (TdP). According to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. However, if concurrent therapy is considered essential, ECG monitoring is recommended.
    Fluphenazine: (Minor) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Fluphenazine is associated with a possible risk for QT prolongation.
    Fluticasone: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Fluticasone; Salmeterol: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Fluticasone; Vilanterol: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Fluvoxamine: (Severe) Due to the similarity in pharmacology of citalopram and fluvoxamine and the potential for serious adverse reactions, including serotonin syndrome, QT prolongation, and torsade de pointes (TdP), these selective serotonin reuptake inhibitors (SSRIs) should not be administered together. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Also, both citalopram and fluvoxamine have been associated with QT prolongation and torsade de pointes (TdP), which could theoretically result in additive effects on the QT interval. It is advisable to monitor for signs and symptoms of serotonin syndrome during an overlapping transition from one SSRI to another SSRI.
    Fondaparinux: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like fondaparinux. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
    Formoterol; Mometasone: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Fosamprenavir: (Major) CYP3A4 is involved in the metabolism of citalopram and the anti-retroviral protease inhibitors may increase plasma concentrations of citalopram through CYP3A4 inhibition. Because citalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease citalopram clearance.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as citalopram. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Citalopram causes dose-dependent QT interval prolongation. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Frovatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering frovatriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and SSRIs. Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue the SSRI and frovatriptan and initiate symptomatic treatment if serotonin syndrome occurs.
    Furosemide: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Gemifloxacin: (Major) Concurrent use of citalopram and gemifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Gemifloxacin may also prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
    Gemtuzumab Ozogamicin: (Major) Avoid coadministration of gemtuzumab ozogamicin with citalopram due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Citalopram causes dose-dependent QT interval prolongation.
    Gilteritinib: (Major) Avoid coadministration of citalopram with gilteritinib due to the potential for decreased response to citalopram and an additive risk of QT prolongation. If concurrent therapy is considered essential, ECG monitoring is recommended. Gilteritinib inhibits human 5HT2B receptor or sigma nonspecific receptors, which may reduce the effects of drugs like citalopram that target these receptors. In addition, both drugs have been associated with QT prolongation.
    Glasdegib: (Major) Avoid coadministration of glasdegib with citalopram due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Citalopram causes dose-dependent QT interval prolongation.
    Goserelin: (Major) Coadministration of citalopram with goserelin is not recommended due to the risk of QT prolongation. If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Androgen deprivation therapy (i.e., goserelin) may prolong the QT/QTc interval.
    Granisetron: (Major) Because of the potential risk and severity of serotonin syndrome or QT prolongation, use caution and monitor closely when administering granisetron with other drugs that have serotonergic properties or may prolong the QT interval, such as citalopram. If serotonin syndrome is suspected, discontinue granisetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. In addition, granisetron has been associated with QT prolongation. According to the product labeling, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences.
    Grapefruit juice: (Moderate) Advise patients that are therapeutically stable on citalopram not to alter their consumption of grapefruit juice. Patients who are newly started on citalopram should not consume grapefruit juice. The inhibition of CYP3A4 via grapefruit juice may lead to elevated serum concentrations of citalopram, but the clinical significance of this interaction is not known.
    Guaifenesin; Hydrocodone: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like hydrocodone with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like hydrocodone with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Halofantrine: (Severe) Halofantrine has an established causal association with QT prolongation and torsade de pointes and is contraindicated for use with other agents that can prolong the QT interval, such as citalopram.
    Halogenated Anesthetics: (Major) Halogenated anesthetics are associated with a risk for QT prolongation. Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Haloperidol: (Major) Coadministration of citalopram and haloperidol should be avoided. Citalopram causes dose-dependent QT interval prolongation, and haloperidol is associated with a possible risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. In addition, because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering citalopram with drugs that are dopamine antagonists such as haloperidol. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. In addition, citalopram mildly inhibits the CYP2D6. This can result in increased concentrations of some drugs metabolized via the same pathway, including haloperidol. Patients receiving these combinations should be monitored for the emergence of serotonin syndrome, neuroleptic malignant syndrome-like reactions, or other adverse effects.
    Halothane: (Major) Halogenated anesthetics are associated with a risk for QT prolongation. Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Heparin: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like heparin. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
    Histrelin: (Major) Coadministration of citalopram with histrelin is not recommended due to the risk of QT prolongation. If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval.
    Homatropine; Hydrocodone: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like hydrocodone with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Hydrochlorothiazide, HCTZ: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Hydrochlorothiazide, HCTZ; Irbesartan: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Hydrochlorothiazide, HCTZ; Lisinopril: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Hydrochlorothiazide, HCTZ; Losartan: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia. (Minor) Citalopram mildly inhibits the hepatic CYP2D6 isoenzyme at therapeutic doses. This can result in increased concentrations of drugs metabolized via the same pathway, including metoprolol.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Hydrochlorothiazide, HCTZ; Propranolol: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia. (Minor) Citalopram mildly inhibits the hepatic CYP2D6 isoenzyme at therapeutic doses. This can result in increased concentrations of drugs metabolized via the same pathway, including propranolol. Increased serum levels of the beta-blockers could result in alterations in cardioselectivity or other clinical effects.
    Hydrochlorothiazide, HCTZ; Quinapril: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Hydrochlorothiazide, HCTZ; Spironolactone: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Hydrochlorothiazide, HCTZ; Telmisartan: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia. (Minor) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with telmisartan, a weak CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Hydrochlorothiazide, HCTZ; Triamterene: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Hydrocodone: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like hydrocodone with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Hydrocodone; Ibuprofen: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like hydrocodone with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Hydrocodone; Phenylephrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like hydrocodone with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like hydrocodone with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like hydrocodone with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Hydrocodone; Pseudoephedrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like hydrocodone with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Hydrocortisone: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and citalopram. Hydroxychloroquine increases the QT interval and should not be administered with other drugs known to prolong the QT interval. Ventricular arrhythmias and torsade de pointes have been reported with the use of hydroxychloroquine. Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Hydroxyzine: (Major) Avoid coadministration of hydroxyzine and citalopram due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Monitor ECG for QT prolongation if coadministration is required. Citalopram causes dose-dependent QT interval prolongation. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Severe) According to the manufacturer of citalopram, treatment initiation with citalopram is contraindicated in patients currently receiving intravenous (IV) methylene blue due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than citalopram (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving citalopram and requiring urgent treatment with IV methylene blue, citalopram should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits outweigh the risks. The patient should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Citalopram may be re-initiated 24 hours after the last dose of methylene blue. Results from an in vitro study indicate that methylene blue is a potent, reversible inhibitor of the monoamine oxidase type A enzyme (MAO-A). MAO-A is responsible for the metabolism of serotonin; therefore, concurrent use of an MAO-A inhibitor with a serotonergic agent may result in a clinically significant interaction. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent, in patients receiving SSRIs, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with IV methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. One case describes a patient receiving citalopram who experienced agitation, restlessness, pupil dilation with sluggish response to light, myoclonic movements of the lower limbs, and brisk reflexes following an infusion of methylene blue, while another patient receiving paroxetine developed tachycardia, agitation, dystonia and abnormal eye movements. During a retrospective study of 193 surgical patients who had received a methylene blue injection, it was found that all 12 of the patients who experienced postoperative neurological sequelae had been taking a serotonin reuptake inhibitor preoperatively. One of the 12 patients experienced cardiopulmonary arrest and died. Of the remaining 181 patients who did not experience neurological sequelae, 8.8% were taking a serotonin reuptake inhibitor. Published interaction reports between IV methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and coma. Signs and symptoms of serotonin syndrome include fever, diaphoresis, shivering, myoclonus, tremor, tachycardia, diarrhea, nausea, headache, incoordination, mental status changes (e.g., agitation, confusion), hyperreflexia, seizures, and coma. (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin.
    Ibuprofen; Oxycodone: (Moderate) The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue the suspected drugs if serotonin syndrome is suspected and manage cliinically. There has been a case report of possible serotonin syndrome caused by the combination of oxycodone and selective serotonin reuptake inhbitors (SSRIs).
    Ibutilide: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with citalopram, a CYP3A substrate, as citalopram toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Iloperidone: (Major) Concurrent use of iloperidone and citalopram should be avoided if possible. Citalopram causes dose-dependent QT interval prolongation and iloperidone is associated with a risk for QT prolongation and torsade de pointes (TdP). According to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. However, if concurrent therapy is considered essential, ECG monitoring is recommended. In addition, citalopram is a weak inhibitor of CYP2D6, and increased plasma concentrations of antipsychotics partially metabolized via CYP2D6, such as iloperidone, may occur. Decreased metabolism of iloperidone may lead to clinically important adverse reactions of antipsychotics such as extrapyramidal symptoms.
    Imipramine: (Major) Citalopram causes dose-dependent QT interval prolongation and tricyclic antidepressants are associated with a possible risk of QT prolongation and torsade de pointes (TdP). According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. In addition, because of the potential risk and severity of serotonin syndrome, caution should be observed when administering citalopram with other drugs that have serotonergic properties such as tricyclic antidepressants. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Clinicians should also be alert for pharmacokinetic interactions between tricyclic antidepressants (TCAs) and SSRIs. Citalopram is a weak inhibitor of CYP2D6, the isoenzyme responsible for metabolism of many of the tricyclic antidepressants. Coadministration of citalopram and imipramine did not significantly affect the plasma concentrations of either drug. However, the concentration of desipramine, the primary metabolite of imipramine, was increased by 50%. The clinical significance of the elevation in desipramine concentration is unknown. However, symptoms of toxicity, including seizures, have been reported when drugs from these 2 classes were used together. A decreased dosage of the TCA or the avoidance of concomitant SSRI therapy should be considered.
    Indapamide: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Indinavir: (Major) CYP3A4 is involved in the metabolism of citalpram. Anti-retroviral protease inhibitors may increase plasma concentrations of citalopram through CYP3A4 inhibition. Because citalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease citalopram clearance.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with citalopram due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes at baseline, after treatment initiation, and periodically during therapy. Inotuzumab has been associated with QT interval prolongation. Citalopram causes dose-dependent QT interval prolongation.
    Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with citalopram may result in increased serum concentrations of citalopram. Citalopram is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
    Isocarboxazid: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with selective serotonin reuptake inhibitors (SSRIs). MAOIs should not be used within 5 weeks of discontinuing treatment with fluoxetine or within 14 days of discontinuing treatment with other SSRIs. Conversely, SSRIs should not be initiated within 14 days of stopping an MAOI. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Isoflurane: (Major) Halogenated anesthetics are associated with a risk for QT prolongation. Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Isoniazid, INH: (Major) The maximum adult dose of citalopram should not exceed 20 mg/day with isoniazid, INH, which inhibits CYP2C19. Concurrent use of isoniazid and citalopram, an SSRI, should be approached with caution. Coadministration of isoniazid, INH and citalopram may result in increased risk of QT prolongation from increased citalopram exposure. Isoniazid is also chemically related to iproniazid, a drug that was known to possess monoamine oxidase (MAO) inhibiting activity, and INH may produce clinical symptoms consistent with serotonergic excess when combined with citalopram, including serotonin syndrome. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be implemented.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) The maximum adult dose of citalopram should not exceed 20 mg/day with isoniazid, INH, which inhibits CYP2C19. Concurrent use of isoniazid and citalopram, an SSRI, should be approached with caution. Coadministration of isoniazid, INH and citalopram may result in increased risk of QT prolongation from increased citalopram exposure. Isoniazid is also chemically related to iproniazid, a drug that was known to possess monoamine oxidase (MAO) inhibiting activity, and INH may produce clinical symptoms consistent with serotonergic excess when combined with citalopram, including serotonin syndrome. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be implemented. (Moderate) Citalopram is metabolized by CYP2C19 and CYP3A4. Rifampin can induce the metabolism of various CYP450 isoenzymes, including those involved in citalopram metabolism. Although no clinical data are available to support a clinically significant interaction, citalopram may need to be administered in higher doses in patients chronically taking rifampin.
    Isoniazid, INH; Rifampin: (Major) The maximum adult dose of citalopram should not exceed 20 mg/day with isoniazid, INH, which inhibits CYP2C19. Concurrent use of isoniazid and citalopram, an SSRI, should be approached with caution. Coadministration of isoniazid, INH and citalopram may result in increased risk of QT prolongation from increased citalopram exposure. Isoniazid is also chemically related to iproniazid, a drug that was known to possess monoamine oxidase (MAO) inhibiting activity, and INH may produce clinical symptoms consistent with serotonergic excess when combined with citalopram, including serotonin syndrome. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be implemented. (Moderate) Citalopram is metabolized by CYP2C19 and CYP3A4. Rifampin can induce the metabolism of various CYP450 isoenzymes, including those involved in citalopram metabolism. Although no clinical data are available to support a clinically significant interaction, citalopram may need to be administered in higher doses in patients chronically taking rifampin.
    Itraconazole: (Major) Avoid coadministration of citalopram and itraconazole due to the potential for additive effects on the QT interval; increased exposure to citalopram is also possible. Both citalopram and itraconazole are associated with QT prolongation; coadministration may increase this risk. If concurrent therapy is considered essential, ECG monitoring is recommended. In addition, because CYP3A4 is one of the primary enzymes involved in the metabolism of citalopram, coadministration of a strong CYP3A4 inhibitor like itraconazole might be expected to decrease the metabolism of citalopram. However, coadministration of another strong CYP3A4 inhibitor did not significantly affect the pharmacokinetics of citalopram.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib with citalopram due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Citalopram causes dose-dependent QT interval prolongation.
    Kava Kava, Piper methysticum: (Moderate) The German Commission E and other groups warn that any substances that act on the CNS, including SSRIs, may interact with the phytomedicinal kava kava, Piper methysticum. These interactions are probably pharmacodynamic in nature, or result from additive mechanisms of action.
    Ketoconazole: (Major) Avoid coadministration of citalopram and ketoconazole due to the potential for additive effects on the QT interval. If concurrent therapy is considered essential, ECG monitoring is recommended. Use of these drugs together may also increase the risk for breakthrough fungal infections. When ketoconazole was coadministered with citalopram, the Cmax and AUC of ketoconazole decreased by 21% and 10%, respectively, suggesting induction of ketoconazole metabolism by citalopram. Ketoconazole did not alter the pharmacokinetics of citalopram.
    Lansoprazole: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with lansoprazole, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Lansoprazole; Naproxen: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with lansoprazole, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Lapatinib: (Major) Concurrent use of citalopram with lapatinib is not recommended due to the risk of QT prolongation. If concurrent therapy is considered essential, monitor ECGs for QT prolongation and monitor electrolytes; correct electrolyte abnormalities prior to treatment. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Citalopram also causes dose-dependent QT interval prolongation.
    Lefamulin: (Major) Avoid coadministration of lefamulin with citalopram as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, ECG monitoring is recommended during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Citalopram causes dose-dependent QT interval prolongation.
    Lenvatinib: (Major) Avoid coadministration of lenvatinib with citalopram due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Citalopram causes dose-dependent QT interval prolongation.
    Letermovir: (Moderate) Plasma concentrations of citalopram may be increased when administered concurrently with letermovir. The magnitude of this interaction may be increased in patients who are also receiving cyclosporine. Monitor for citalopram-related adverse events. Citalopram is a CYP3A4 substrate. Letermovir is a moderate inhibitor of CYP3A4; however, the combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. In a drug interaction study, concurrent administration of citalopram and another strong CYP3A4 inhibitor did not significantly affect the pharmacokinetics of citalopram.
    Leuprolide: (Major) Coadministration of citalopram with leuprolide is not recommended due to the risk of QT prolongation. If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
    Leuprolide; Norethindrone: (Major) Coadministration of citalopram with leuprolide is not recommended due to the risk of QT prolongation. If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
    Levofloxacin: (Major) Concurrent use of citalopram and levofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Additionally, rare cases of TdP have been spontaneously reported during postmarketing surveillance in patients receiving levofloxacin. Citalopram causes dose-dependent QT interval prolongation.
    Levomethadyl: (Severe) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer of citalopram, ECG monitoring is recommended in patients receiving concurrent drugs that prolong the QT interval. However, drugs with an established causal association with QT prolongation and torsade de pointes which are contraindicated for use with other agents that can prolong the QT interval include levomethadyl.
    Levomilnacipran: (Major) Because of the potential risk and severity of serotonin syndrome, concurrent use of levomilnacipran with other drugs that have serotonergic properties, such as selective serotonin reuptake inhibitors (SSRIs), should generally be avoided. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome is suspected, levomilnacipran and concurrent serotonergic agents should be discontinued.
    Levorphanol: (Moderate) Citalopram impairs metabolism via the CYP2D6 pathway at therapeutic doses. This can result in increased concentrations of drugs metabolized via the same pathway, including some opiate agonists.
    Lidocaine: (Moderate) Concomitant use of systemic lidocaine and citalopram may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; citalopram is a weak CYP1A2 inhibitor.
    Linezolid: (Severe) According to the manufacturer of citalopram, treatment initiation with citalopram is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than citalopram (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving citalopram and requiring urgent treatment with linezolid, citalopram should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Citalopram may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with citalopram can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Serotonin syndrome has been reported in patients receiving either citalopram, escitalopram, fluoxetine, or paroxetine in combination with linezolid.
    Lithium: (Major) Lithium is an effective augmenting agent to antidepressants in treatment-resistant depression; however, lithium has been associated with QT prolongation and should be used cautiously and with close monitoring with other drugs having the potential to prolong the QT interval such as citalopram. In addition, lithium has been reported to have central serotonin-enhancing effects and may interact pharmacodynamically with selective serotonin reuptake inhibitors (SSRIs) such as citalopram to cause serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients should be informed of the possible increased risk of serotonin syndrome. If serotonin syndrome occurs, citalopram and lithium should be discontinued and symptomatic treatment should be initiated. One systematic review and meta-analysis of lithium augmentation of tricyclic and second generation antidepressants in major depression found no difference in discontinuation rate due to adverse events between the lithium and placebo groups. However, there are case reports of neurotoxicity (e.g., confusion, ataxia) as well as fever and seizures when SSRIs have been used with lithium. Neurotoxicity may be more likely to occur in the elderly.
    Lofexidine: (Major) Avoid coadministration of lofexidine and citalopram due to the potential for additive QT prolongation and torsade de pointes (TdP). Monitor ECG for QT prolongation if coadministration is required. Lofexidine prolongs the QT interval, and TdP has been reported during postmarketing use. Citalopram causes dose-dependent QT interval prolongation.
    Long-acting beta-agonists: (Moderate) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with citalopram include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Loperamide: (Major) Loperamide should be avoided in combination with citalopram. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. In addition, the plasma concentrations of loperamide, a CYP2D6 substrate, may be increased when administered concurrently with citalopram, a weak CYP2D6 inhibitor, further increasing the risk of toxicity. If these drugs are used together, monitor for cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, TdP, cardiac arrest) and other loperamide-associated adverse reactions, such as CNS effects.
    Loperamide; Simethicone: (Major) Loperamide should be avoided in combination with citalopram. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. In addition, the plasma concentrations of loperamide, a CYP2D6 substrate, may be increased when administered concurrently with citalopram, a weak CYP2D6 inhibitor, further increasing the risk of toxicity. If these drugs are used together, monitor for cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, TdP, cardiac arrest) and other loperamide-associated adverse reactions, such as CNS effects.
    Lopinavir; Ritonavir: (Major) Concurrent use of citalopram and lopinavir; ritonavir should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Lopinavir; ritonavir is also associated with QT prolongation. In addition, lopinavir; ritonavir inhibits CYP3A4 and citalopram is a CYP3A4 substrate. However, since citalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease citalopram clearance. (Minor) Concurrent use of ritonavir may increase citalopram exposure and treatment-related adverse effects. Ritonavir is a strong CYP3A4 inhibitor. Because CYP3A4 is one of the primary enzymes involved in the metabolism of citalopram, it is expected that strong CYP3A4 inhibitors might decrease the clearance of citalopram. However, coadministration of citalopram and another strong CYP3A4 inhibitor ketoconazole did not significantly affect the pharmacokinetics of citalopram.
    Lorcaserin: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, selective serotonin reuptake inhibitors (SSRIs). Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Low Molecular Weight Heparins: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like low molecular weight heparins. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
    Luliconazole: (Moderate) Theoretically, luliconazole may increase the side effects of citalopram, which is a CYP2C19 and CYP3A4 substrate. Monitor patients for adverse effects of citalopram, such as QT prolongation, serotonin syndrome, and neuroleptic malignant syndrome. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
    Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of citalopram by decreasing its systemic exposure. If used together, a higher dose of citalopram may be required to obtain the desired therapeutic effect. Do not exceed the recommended maximum dose. Citalopram is a CYP3A and CYP2C19 substrate. Lumacaftor; ivacaftor is a strong inducer of CYP3A and has the potential to induce CYP2C19.
    Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as citalopram. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Citalopram causes dose-dependent QT interval prolongation.
    Magnesium Salicylate: (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. A cohort study in > 26,000 patients found that SSRI use alone increased the risk for serious GI bleed by 3.6-fold; when an SSRI was combined with aspirin the risk was increased by > 5-fold. The absolute risk of GI bleed from concomitant therapy with aspirin and a SSRI was low (20/2640 patients) in this cohort study and the clinician may determine that the combined use of these drugs is appropriate.
    Maprotiline: (Major) Because citalopram and maprotiline are associated with a possible risk for QT prolongation and torsade de pointes (TdP), these combinations should be used cautiously and with close monitoring. Monitoring of the ECG is recommended in patients receiving citalopram with other drugs that may prolong the QT interval such as maprotiline. CYP2D6, the primary isoenzyme responsible for the metabolism of maprotiline, is inhibited to some extent by citalopram. Patients receiving maprotiline should be monitored closely for toxicity if an SSRI is added.
    Mefloquine: (Major) Concurrent use of citalopram and mefloquine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. There is evidence that the use of halofantrine after mefloquine also causes significant lengthening of the QTc interval. However, use of mefloquine alone has not been reported to cause QT prolongation.
    Meperidine: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as meperidine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. A 42-year-old man became agitated, restless, diaphoretic, tachycardic, and hypertensive immediately after receipt of meperidine 50 mg intravenously. Two weeks before the incident, the patient had stopped a regimen of the SSRI, fluoxetine. Serotonin syndrome was suspected, as fluoxetine and norfluoxetine have long half-lives, and previous meperidine receipt during a time when the patient had not been taking fluoxetine was uneventful. If serotonin syndrome is suspected, the SSRI and concurrent serotonergic agents should be discontinued.
    Meperidine; Promethazine: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as meperidine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. A 42-year-old man became agitated, restless, diaphoretic, tachycardic, and hypertensive immediately after receipt of meperidine 50 mg intravenously. Two weeks before the incident, the patient had stopped a regimen of the SSRI, fluoxetine. Serotonin syndrome was suspected, as fluoxetine and norfluoxetine have long half-lives, and previous meperidine receipt during a time when the patient had not been taking fluoxetine was uneventful. If serotonin syndrome is suspected, the SSRI and concurrent serotonergic agents should be discontinued. (Major) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Promethazine carries a possible risk of QT prolongation.
    Mesoridazine: (Severe) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer of citalopram, ECG monitoring is recommended in patients receiving concurrent drugs that prolong the QT interval. Conventional antipsychotics having an established causal association with QT prolongation and TdP (torsade de pointes) and which are contraindicated for use with other agents that can prolong the QT interval include mesoridazine. In addition, citalopram mildly inhibits the hepatic CYP2D6 isoenzyme at therapeutic doses. This can result in increased concentrations of some drugs metabolized via the same pathway, including phenothiazines, possibly causing serotonin syndrome.
    Methadone: (Major) Coadministration may increase the risk of serotonin syndrome, QT prolongation, or torsade de pointes (TdP). Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer of citalopram, ECG monitoring is recommended in patients receiving concurrent drugs that prolong the QT interval. The need to coadminister methadone with drugs known to prolong the QT interval should be done with extreme caution and a careful assessment of treatment risks versus benefits. Methadone is associated with an increased risk for QT prolongation and TdP, especially at higher doses (greater than 200 mg/day but averaging approximately 400 mg/day in adult patients). Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. In addition, both citalopram and methadone have central serotonergic properties and serotonin syndrome is possible. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
    Methazolamide: (Moderate) Caution is advisable during concurrent use of citalopram and methazolamide as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with citalopram.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Severe) According to the manufacturer of citalopram, treatment initiation with citalopram is contraindicated in patients currently receiving intravenous (IV) methylene blue due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than citalopram (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving citalopram and requiring urgent treatment with IV methylene blue, citalopram should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits outweigh the risks. The patient should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Citalopram may be re-initiated 24 hours after the last dose of methylene blue. Results from an in vitro study indicate that methylene blue is a potent, reversible inhibitor of the monoamine oxidase type A enzyme (MAO-A). MAO-A is responsible for the metabolism of serotonin; therefore, concurrent use of an MAO-A inhibitor with a serotonergic agent may result in a clinically significant interaction. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent, in patients receiving SSRIs, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with IV methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. One case describes a patient receiving citalopram who experienced agitation, restlessness, pupil dilation with sluggish response to light, myoclonic movements of the lower limbs, and brisk reflexes following an infusion of methylene blue, while another patient receiving paroxetine developed tachycardia, agitation, dystonia and abnormal eye movements. During a retrospective study of 193 surgical patients who had received a methylene blue injection, it was found that all 12 of the patients who experienced postoperative neurological sequelae had been taking a serotonin reuptake inhibitor preoperatively. One of the 12 patients experienced cardiopulmonary arrest and died. Of the remaining 181 patients who did not experience neurological sequelae, 8.8% were taking a serotonin reuptake inhibitor. Published interaction reports between IV methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and coma. Signs and symptoms of serotonin syndrome include fever, diaphoresis, shivering, myoclonus, tremor, tachycardia, diarrhea, nausea, headache, incoordination, mental status changes (e.g., agitation, confusion), hyperreflexia, seizures, and coma.
    Methyclothiazide: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Methylene Blue: (Severe) According to the manufacturer of citalopram, treatment initiation with citalopram is contraindicated in patients currently receiving intravenous (IV) methylene blue due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than citalopram (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving citalopram and requiring urgent treatment with IV methylene blue, citalopram should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits outweigh the risks. The patient should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Citalopram may be re-initiated 24 hours after the last dose of methylene blue. Results from an in vitro study indicate that methylene blue is a potent, reversible inhibitor of the monoamine oxidase type A enzyme (MAO-A). MAO-A is responsible for the metabolism of serotonin; therefore, concurrent use of an MAO-A inhibitor with a serotonergic agent may result in a clinically significant interaction. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent, in patients receiving SSRIs, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with IV methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. One case describes a patient receiving citalopram who experienced agitation, restlessness, pupil dilation with sluggish response to light, myoclonic movements of the lower limbs, and brisk reflexes following an infusion of methylene blue, while another patient receiving paroxetine developed tachycardia, agitation, dystonia and abnormal eye movements. During a retrospective study of 193 surgical patients who had received a methylene blue injection, it was found that all 12 of the patients who experienced postoperative neurological sequelae had been taking a serotonin reuptake inhibitor preoperatively. One of the 12 patients experienced cardiopulmonary arrest and died. Of the remaining 181 patients who did not experience neurological sequelae, 8.8% were taking a serotonin reuptake inhibitor. Published interaction reports between IV methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and coma. Signs and symptoms of serotonin syndrome include fever, diaphoresis, shivering, myoclonus, tremor, tachycardia, diarrhea, nausea, headache, incoordination, mental status changes (e.g., agitation, confusion), hyperreflexia, seizures, and coma.
    Methylergonovine: (Moderate) Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been co-administered with SSRI's (e.g., citalopram), which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
    Methylphenidate: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as methylphenidate and selective serotonin reuptake inhibitors (SSRIs). There are rare reports of serotonin syndrome occurring during use of an SSRI and methylphenidate. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented. Additionally, human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of SSRIs. A dose adjustment of the SSRI may be required when initiating or discontinuing methylphenidate.
    Methylprednisolone: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Methysergide: (Moderate) Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been co-administered with SSRI's (e.g., citalopram), which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
    Metolazone: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Metoprolol: (Minor) Citalopram mildly inhibits the hepatic CYP2D6 isoenzyme at therapeutic doses. This can result in increased concentrations of drugs metabolized via the same pathway, including metoprolol.
    Metronidazole: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include citalopram.
    Mexiletine: (Moderate) Citalopram mildly inhibits the hepatic CYP2D6 isoenzyme at therapeutic doses. This can result in increased concentrations of drugs metabolized via the same pathway, including mexiletine.
    Midostaurin: (Major) Avoid the concomitant use midostaurin and citalopram if possible; both drugs have been reported to increase the QT interval. If use of these drugs together is necessary, monitor electrocardiograms. Discontinue citalopram in patients who experience persistent QTc measurements above 500 milliseconds. In clinical trials, QT prolongation was reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Citalopram causes dose-dependent QT interval prolongation.
    Mifepristone: (Major) Avoid use of these drugs together if possible; consider alternative therapies. Citalopram causes dose-dependent QT interval prolongation.The concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Mifepristone, when used chronically for hormonal conditions like Cushing's syndrome, has been associated with dose-dependent prolongation of the QT interval. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used.
    Milnacipran: (Major) Because of the potential risk and severity of serotonin syndrome, concurrent use of milnacipran with other drugs that have serotonergic properties, such as the selective serotonin reuptake inhibitors (SSRIs), should generally be avoided. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome is suspected, milnacipran and concurrent serotonergic agents should be discontinued.
    Mirtazapine: (Major) Concomitant use of mirtazapine and citalopram may increase the risk of serotonin syndrome, QT prolongation, and torsade de pointes. Citalopram causes dose-dependent QT interval prolongation. The manufacturer of citalopram recommends avoidance of other drugs that prolong the QT interval. If concurrent therapy is required, ECG monitoring is recommended. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during use of mirtazapine, primarily after overdose or in patients with risk factors for QT prolongation (e.g., concurrent use of other medications associated with QT prolongation). Both mirtazapine and SSRIs such as citalopram have central serotonin-enhancing effects, and case reports suggest that serotonin syndrome is possible. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
    Mitotane: (Moderate) Use caution if mitotane and citalopram are used concomitantly, and monitor for decreased efficacy of citalopram and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and citalopram is a CYP3A4 substrate in vitro; coadministration may result in decreased plasma concentrations of citalopram.
    Modafinil: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with modafinil, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Mometasone: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Monoamine oxidase inhibitors: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with selective serotonin reuptake inhibitors (SSRIs). MAOIs should not be used within 5 weeks of discontinuing treatment with fluoxetine or within 14 days of discontinuing treatment with other SSRIs. Conversely, SSRIs should not be initiated within 14 days of stopping an MAOI. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Morphine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like morphine with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Morphine; Naltrexone: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like morphine with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Moxifloxacin: (Major) Concurrent use of citalopram and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Moxifloxacin has also been associated with prolongation of the QT interval. Additionally, post-marketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded.
    Naproxen; Sumatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sumatriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and SSRIs. Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue the SSRI and sumatriptan and initiate symptomatic treatment if serotonin syndrome occurs.
    Naratriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering naratriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and SSRIs. Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue the SSRI and naratriptan and initiate symptomatic treatment if serotonin syndrome occurs.
    Nebivolol: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with citalopram. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as citalopram, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible.
    Nebivolol; Valsartan: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with citalopram. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as citalopram, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible.
    Nefazodone: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as nefazodone and citalopram. In addition, nefazodone is a strong inhibitor of CYP3A4 and citalopram is a partial CYP3A4 substrate. Concurrent use may increase the risk of citalopram-related adverse effects such as QT prolongation and torsade de pointes (TdP). Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least one case report of serotonin syndrome from the concurrent use of nefazodone and a selective serotonin reuptake inhibitor (i.e., paroxetine) has been published. Additionally, when a 200 mg dose of nefazodone was administered to subjects who had been receiving fluoxetine for 1 week, there was an increased incidence of transient serotonin-related adverse events. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
    Nelfinavir: (Major) CYP3A4 is involved in the metabolism of citalpram. Anti-retroviral protease inhibitors may increase plasma concentrations of citalopram through CYP3A4 inhibition. Because citalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease citalopram clearance.
    Netupitant, Fosnetupitant; Palonosetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution and monitor closely when administering palonosetron with other drugs that have serotonergic properties, such as citalopram. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Nicardipine: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with nicardipine, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Nilotinib: (Major) Avoid coadministration of nilotinib with citalopram due to an increased risk for QT prolongation. Citalopram causes dose-dependent QT interval prolongation. Sudden death and QT interval prolongation have occurred in patients who received nilotinib therapy.
    Nitroglycerin: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
    Nonsteroidal antiinflammatory drugs: (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and nonsteroidal antiinflammatory drugs (NSAIDs) may increase the risk of bleeding, including an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of NSAIDs. Additionally, NSAIDs impair the gastric mucosa defenses by inhibiting prostaglandin formation. A cohort study in more than 26,000 patients found that SSRI use alone increased the risk for serious GI bleed by 3.6-fold; when an SSRI was combined with NSAIDs, the risk was increased by more than 12.2-fold. The absolute risk of GI bleed from concomitant therapy with NSAIDs and a SSRI was low (17/4107 patients).
    Norfloxacin: (Major) Concurrent use of citalopram and norfloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Quinolones have also been associated with QT prolongation and TdP. For norfloxacin specifically, extremely rare cases of TdP were reported during post-marketing surveillance. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Nortriptyline: (Major) Citalopram causes dose-dependent QT interval prolongation and tricyclic antidepressants are associated with a possible risk of QT prolongation and torsade de pointes (TdP). According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. In addition, because of the potential risk and severity of serotonin syndrome, caution should be observed when administering citalopram with other drugs that have serotonergic properties such as tricyclic antidepressants. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Clinicians should also be alert for pharmacokinetic interactions between tricyclic antidepressants (TCAs) and SSRIs. Citalopram is a weak inhibitor of CYP2D6, the isoenzyme responsible for metabolism of many of the tricyclic antidepressants. Coadministration of citalopram and imipramine did not significantly affect the plasma concentrations of either drug. However, the concentration of desipramine, the primary metabolite of imipramine, was increased by 50%. The clinical significance of the elevation in desipramine concentration is unknown. However, symptoms of toxicity, including seizures, have been reported when drugs from these 2 classes were used together. A decreased dosage of the TCA or the avoidance of concomitant SSRI therapy should be considered.
    Octreotide: (Major) Concurrent use of citalopram with octreotide is not recommended due to the potential for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Ofloxacin: (Major) Concurrent use of citalopram and ofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Some quinolones, including ofloxacin, have also been associated with QT prolongation. Additionally, post-marketing surveillance for ofloxacin has identified very rare cases of TdP.
    Olanzapine: (Major) Concurrent use of olanzapine and citalopram should be avoided if possible. Citalopram causes dose-dependent QT interval prolongation and olanzapine is associated with a risk for QT prolongation and torsade de pointes (TdP). According to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. However, if concurrent therapy is considered essential, ECG monitoring is recommended.
    Ombitasvir; Paritaprevir; Ritonavir: (Minor) Concurrent use of ritonavir may increase citalopram exposure and treatment-related adverse effects. Ritonavir is a strong CYP3A4 inhibitor. Because CYP3A4 is one of the primary enzymes involved in the metabolism of citalopram, it is expected that strong CYP3A4 inhibitors might decrease the clearance of citalopram. However, coadministration of citalopram and another strong CYP3A4 inhibitor ketoconazole did not significantly affect the pharmacokinetics of citalopram.
    Omeprazole: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with omeprazole, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Omeprazole; Sodium Bicarbonate: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with omeprazole, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Ondansetron: (Major) Coadministration of ondansetron and citalopram is not recommended due to the potential for QT prolongation. If concurrent therapy is considered essential, ECG monitoring is recommended. Ondansetron has been associated with a dose-related increase in the QT interval and postmarketing reports of torsade de pointes (TdP). Citalopram causes dose-dependent QT interval prolongation.
    Oritavancin: (Moderate) Coadministration of oritavancin and citalopram may result in increases or decreases in citalopram exposure and may increase side effects or decrease efficacy of citalopram. Citalopram is metabolized by CYP3A4 and CYP2C19. Oritavancin weakly induces CYP3A4, while weakly inhibiting CYP2C19. If these drugs are administered concurrently, monitor the patient for signs of toxicity or lack of efficacy.
    Osimertinib: (Major) According to the manufacturer of citalopram, concurrent use with other medications that prolong the QT interval, such as osimertinib is not recommended. If coadministration is unavoidable, monitor electrolytes and ECGs for QT prolongation; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib; citalopram also causes dose-dependent QT interval prolongation.
    Oxaliplatin: (Major) Coadministration of citalopram with oxaliplatin is not recommended due to an additive risk of QT prolongation. If unavoidable, monitor ECGs and electrolytes periodically during therapy; correct electrolyte abnormalities prior to administration of oxaliplatin. Citalopram causes dose-dependent QT interval prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in post-marketing experience.
    Oxcarbazepine: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with oxcarbazepine, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Oxycodone: (Moderate) The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue the suspected drugs if serotonin syndrome is suspected and manage cliinically. There has been a case report of possible serotonin syndrome caused by the combination of oxycodone and selective serotonin reuptake inhbitors (SSRIs).
    Paliperidone: (Major) Concurrent use of paliperidone and citalopram should be avoided if possible. Citalopram causes dose-dependent QT interval prolongation. Paliperidone is associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturers of both paliperidone and citalopram, concurrent use with other drugs that prolong the QT interval is not recommended. If concurrent use is required, ECG monitoring is recommended. Close monitoring is essential in patients with known risk factors for cardiac disease or arrhythmias.
    Palonosetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution and monitor closely when administering palonosetron with other drugs that have serotonergic properties, such as citalopram. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Panobinostat: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include citalopram.
    Paroxetine: (Severe) Due to the similarity in pharmacology of paroxetine and citalopram and the potential for serious adverse reactions, including serotonin syndrome, these selective serotonin reuptake inhibitors (SSRIs) should not be administered together. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. It is advisable to monitor for signs and symptoms of serotonin syndrome during an overlapping transition from one SSRI to another SSRI.
    Pasireotide: (Major) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval, such as pasireotide, is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolongs the QT interval, such as citalopram, is not advised; pazopanib has been reported to prolongs the QT interval. If pazopanib and the other drug must be continued, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and citalopram, a CYP3A4 substrate, may cause an increase in systemic concentrations of citalopram. Use caution if coadministration is necessary.
    Pentamidine: (Major) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with citalopram include intravenous pentamidine, which has been associated with QT prolongation.
    Pentazocine: (Major) Because of the potential risk and severity of serotonin syndrome reactions, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as pentazocine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome occurs, discontinue the offending agent(s) and institute appropriate therapy.
    Pentazocine; Naloxone: (Major) Because of the potential risk and severity of serotonin syndrome reactions, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as pentazocine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome occurs, discontinue the offending agent(s) and institute appropriate therapy.
    Pentosan: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and pentosan, which has weak anticoagulant properties. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
    Pergolide: (Moderate) Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been co-administered with SSRI's (e.g., citalopram), which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
    Perphenazine: (Minor) Citalopram causes dose-dependent QT interval prolongation and perphenazine is associated with a possible risk for QT prolongation and torsade de pointes (TdP). Per the manufacturer of citalopram, ECG monitoring is recommended in patients receiving concurrent drugs that prolong the QT interval.
    Perphenazine; Amitriptyline: (Major) Citalopram causes dose-dependent QT interval prolongation and tricyclic antidepressants are associated with a possible risk of QT prolongation and torsade de pointes (TdP). According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. In addition, because of the potential risk and severity of serotonin syndrome, caution should be observed when administering citalopram with other drugs that have serotonergic properties such as tricyclic antidepressants. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Clinicians should also be alert for pharmacokinetic interactions between tricyclic antidepressants (TCAs) and SSRIs. Citalopram is a weak inhibitor of CYP2D6, the isoenzyme responsible for metabolism of many of the tricyclic antidepressants. Coadministration of citalopram and imipramine did not significantly affect the plasma concentrations of either drug. However, the concentration of desipramine, the primary metabolite of imipramine, was increased by 50%. The clinical significance of the elevation in desipramine concentration is unknown. However, symptoms of toxicity, including seizures, have been reported when drugs from these 2 classes were used together. A decreased dosage of the TCA or the avoidance of concomitant SSRI therapy should be considered. (Minor) Citalopram causes dose-dependent QT interval prolongation and perphenazine is associated with a possible risk for QT prolongation and torsade de pointes (TdP). Per the manufacturer of citalopram, ECG monitoring is recommended in patients receiving concurrent drugs that prolong the QT interval.
    Phenelzine: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with selective serotonin reuptake inhibitors (SSRIs). MAOIs should not be used within 5 weeks of discontinuing treatment with fluoxetine or within 14 days of discontinuing treatment with other SSRIs. Conversely, SSRIs should not be initiated within 14 days of stopping an MAOI. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Phentermine: (Moderate) Use phentermine and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) together with caution; use together may be safe and efficacious for some patients based on available data, provided the patient is on a stable antidepressant regimen and receives close clinical monitoring. Regular appointments to assess the efficacy of the weight loss treatment, the emergence of adverse events, and blood pressure monitoring are recommended. Watch for excessive serotonergic effects. Phentermine is related to the amphetamines, and there has been historical concern that phentermine might exhibit potential to cause serotonin syndrome or cardiovascular or pulmonary effects when combined with serotonergic agents. One case report has been received of adverse reactions with phentermine and fluoxetine. However, recent data suggest that phentermine's effect on MAO inhibition and serotonin augmentation is minimal at therapeutic doses, and that phentermine does not additionally increase plasma serotonin levels when combined with other serotonergic agents. In large controlled clinical studies, patients were allowed to start therapy with phentermine or phentermine; topiramate extended-release for obesity along with their antidepressants (e.g., SSRIs or SNRIs, but not MAOIs or TCAs) as long as the antidepressant dose had been stable for at least 3 months prior to the initiation of phentermine, and the patient did not have suicidal ideation or more than 1 episode of major depression documented. In analyses of the results, therapy was generally well tolerated, especially at lower phentermine doses, based on discontinuation rates and reported adverse events. Because depression and obesity often coexist, the study data may be important to providing optimal co-therapies.
    Phentermine; Topiramate: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with topiramate, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors. In addition, concurrent use of topiramate and drugs that affect platelet function such as selective serotonin reuptake inhibitors (SSRIs) may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. (Moderate) Use phentermine and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) together with caution; use together may be safe and efficacious for some patients based on available data, provided the patient is on a stable antidepressant regimen and receives close clinical monitoring. Regular appointments to assess the efficacy of the weight loss treatment, the emergence of adverse events, and blood pressure monitoring are recommended. Watch for excessive serotonergic effects. Phentermine is related to the amphetamines, and there has been historical concern that phentermine might exhibit potential to cause serotonin syndrome or cardiovascular or pulmonary effects when combined with serotonergic agents. One case report has been received of adverse reactions with phentermine and fluoxetine. However, recent data suggest that phentermine's effect on MAO inhibition and serotonin augmentation is minimal at therapeutic doses, and that phentermine does not additionally increase plasma serotonin levels when combined with other serotonergic agents. In large controlled clinical studies, patients were allowed to start therapy with phentermine or phentermine; topiramate extended-release for obesity along with their antidepressants (e.g., SSRIs or SNRIs, but not MAOIs or TCAs) as long as the antidepressant dose had been stable for at least 3 months prior to the initiation of phentermine, and the patient did not have suicidal ideation or more than 1 episode of major depression documented. In analyses of the results, therapy was generally well tolerated, especially at lower phentermine doses, based on discontinuation rates and reported adverse events. Because depression and obesity often coexist, the study data may be important to providing optimal co-therapies.
    Phenylephrine; Promethazine: (Major) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Promethazine carries a possible risk of QT prolongation.
    Phenytoin: (Moderate) Citalopram is metabolized by CYP2C19 and CYP3A4. Phenytoin can induce the metabolism of various CYP 450 isoenzymes, including those involved in citalopram metabolism. Although no clinical data are available to support a clinically significant interaction, citalopram may need to be administered in higher doses in patients chronically taking phenytoin.
    Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as citalopram. Citalopram causes dose-dependent QT interval prolongation. Coadministration may increase the risk for QT prolongation. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Pimozide: (Severe) Pimozide is contraindicated for use with selective serotonin reuptake inhibitors (SSRIs) due to an increased risk of QT prolongation and torsade de pointes (TdP). Pimozide is thought to be primarily metabolized through CYP3A4, and to a lesser extent, CYP1A2 and CYP2D6. Elevated plasma concentrations of pimozide occurring through inhibition of one or more of these isoenzymes by SSRIs can lead to QT prolongation, ventricular arrhythmias, and sudden death. Additionally, most SSRIs are also associated with QT prolongation, further increasing the risk of additive QT prolongation.
    Pirfenidone: (Minor) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with pirfenidone, a weak in vitro CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Pitolisant: (Major) Avoid coadministration of pitolisant with citalopram as concurrent use may increase the risk of QT prolongation. If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Pitolisant prolongs the QT interval.
    Posaconazole: (Severe) The concurrent use of posaconazole and citalopram is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of citalopram. Using these drugs in combination may result in elevated citalopram plasma concentrations, causing an increased risk for adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as citalopram.
    Prasugrel: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving prasugrel. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
    Prednisolone: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Prednisone: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Primaquine: (Major) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include citalopram.
    Procainamide: (Major) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with citalopram include procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP).
    Procarbazine: (Major) Procarbazine is a weak monoamine oxidase inhibitor (MAOI). Although procarbazine appears to be less likely than other MAOIs to produce serious drug interactions, clinicians should avoid the use of selective serotonin reuptake inhibitors (SSRIs) in patients receiving MAOIs. Fatalities have been reported when fluoxetine was administered to patients receiving MAOIs. Confusion, seizures, severe hypertension, and other, less severe symptoms have also been reported with this drug combination. Non-selective MAOIs inhibit both MAO types A and B. Since serotonin is metabolized by MAO type A, it is thought that this drug interaction may lead to serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. At least 2 weeks should elapse between the discontinuation of MAOI therapy and the start of therapy with an SSRI except fluoxetine. At least 5 weeks should elapse between the discontinuation of fluoxetine therapy and commencement of MAOI therapy. This 5-week period is needed because of the long half-lives of fluoxetine and its principle metabolite norfluoxetine.
    Prochlorperazine: (Minor) Concurrent use of citalopram and prochlorperazine should be avoided. Citalopram causes dose-dependent QT interval prolongation and phenothiazines, such as prochlorperazine, have been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP). According to the manufacturer of citalopram, ECG monitoring is recommended in patients receiving concurrent drugs that prolong the QT interval. In addition, because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering citalopram with drugs that are dopamine antagonists such as phenothiazines. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. In addition, citalopram mildly inhibits the hepatic CYP2D6 isoenzyme at therapeutic doses. This can result in increased concentrations of some drugs metabolized via the same pathway, including phenothiazines. Patients receiving these combinations should be monitored for the emergence of serotonin syndrome, neuroleptic malignant syndrome-like reactions, or other adverse effects.
    Promethazine: (Major) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Promethazine carries a possible risk of QT prolongation.
    Propafenone: (Major) Concurrent use of citalopram and propafenone should be avoided. If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram is associated with a dose-dependent QT prolongation. Propafenone is a Class IC antiarrhythmic which increases the QT interval, largely due to prolongation of the QRS interval. The use of propafenone in conjunction with other drugs that prolong the QT interval has not been studied and is not recommended by the manufacturer due to potential risk for ventricular tachycardia, including torsade de pointes (TdP) and monomorphic ventricular tachycardia. Some SSRIs may inhibit CYP2D6, and can result in increased concentrations of drugs metabolized by this pathway including propafenone, with potential to increase the risk of drug toxicity. Citalopram mildly inhibit the hepatic CYP2D6 isoenzyme.
    Propoxyphene: (Moderate) Citalopram impairs metabolism via the CYP2D6 pathway at therapeutic doses. This can result in increased concentrations of drugs metabolized via the same pathway, including some opiate agonists.
    Propranolol: (Minor) Citalopram mildly inhibits the hepatic CYP2D6 isoenzyme at therapeutic doses. This can result in increased concentrations of drugs metabolized via the same pathway, including propranolol. Increased serum levels of the beta-blockers could result in alterations in cardioselectivity or other clinical effects.
    Protriptyline: (Major) Citalopram causes dose-dependent QT interval prolongation and tricyclic antidepressants are associated with a possible risk of QT prolongation and torsade de pointes (TdP). According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. In addition, because of the potential risk and severity of serotonin syndrome, caution should be observed when administering citalopram with other drugs that have serotonergic properties such as tricyclic antidepressants. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Clinicians should also be alert for pharmacokinetic interactions between tricyclic antidepressants (TCAs) and SSRIs. Citalopram is a weak inhibitor of CYP2D6, the isoenzyme responsible for metabolism of many of the tricyclic antidepressants. Coadministration of citalopram and imipramine did not significantly affect the plasma concentrations of either drug. However, the concentration of desipramine, the primary metabolite of imipramine, was increased by 50%. The clinical significance of the elevation in desipramine concentration is unknown. However, symptoms of toxicity, including seizures, have been reported when drugs from these 2 classes were used together. A decreased dosage of the TCA or the avoidance of concomitant SSRI therapy should be considered.
    Quetiapine: (Major) Concurrent use of quetiapine and citalopram should be avoided if possible. Citalopram causes dose-dependent QT interval prolongation and quetiapine is associated with a risk for QT prolongation and torsade de pointes (TdP). According to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. However, if concurrent therapy is considered essential, ECG monitoring is recommended.
    Quinidine: (Major) Because citalopram and quinidine are associated with QT prolongation, these combinations should be used cautiously and with close monitoring. The manufacturers of quinidine and citalopram recommend an ECG in patients taking either of these drugs in combination with other drugs known to cause QT prolongation.
    Quinine: (Major) Concurrent use of quinine and citalopram should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Citalopram also causes dose-dependent QT interval prolongation. In addition, concentrations of citalopram may be increased with concomitant use of quinine. Citalopram is a CYP3A4 and CYP2D6 substrate and quinine is an inhibitor of both enzymes.
    Rabeprazole: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with rabeprazole, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Ranolazine: (Major) Citalopram causes dose-dependent QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with citalopram include ranolazine. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. The mean increase in QTc is about 6 milliseconds, measured at the tmax of the maximum dosage (1000 mg PO twice daily). However, in 5% of the population studied, increases in the QTc of at least 15 milliseconds have been reported. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Ranolazine is metabolized mainly by CYP3A and to a lesser extent by CYP2D6. Citalopram is a known CYP2D6 inhibitor; coadministration may result in increased plasma concentrations of ranolazine. The manufacturer specifies that no dosage adjustment of ranolazine is necessary when coadministering CYP2D6 inhibitors. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Rasagiline: (Major) It is recommended to avoid concurrent use of rasagiline and antidepressants, including selective serotonin reuptake inhibitors (SSRIs). Severe CNS toxicity with hyperpyrexia has been reported during concurrent use of antidepressants and selective or non-selective MAOIs. During post-marketing use of rasagiline, non-fatal cases of serotonin syndrome have been reported during concomitant antidepressant administration. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. At least 2 weeks should elapse between stopping rasagiline treatment and beginning therapy with any SSRI. Conversely, when discontinuing an SSRI, it is advisable to wait the length of 4 to 5 half-lives of the individual agent being discontinued prior to initiation with rasagiline. At least 5 weeks should elapse between the discontinuation of fluoxetine therapy and initiation of rasagiline; this 5-week period is needed because of the long half-lives of fluoxetine and its active metabolite norfluoxetine. Fluvoxamine is a strong CYP1A2 inhibitor, and rasagiline plasma concentrations may increase up to 2-fold during concurrent use, resulting in the potential for increased adverse events from rasagiline.
    Remifentanil: (Moderate) Concurrent use of remifentanil with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. If concurrent use is necessary, closely monitor the patient, particularly during remifentanil initiation and dosage adjustment. Discontinue remifentanil if serotonin syndrome is suspected.
    Reteplase, r-PA: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with an SSRI.
    Ribociclib: (Major) Avoid coadministration of ribociclib with citalopram due to an increased risk for QT prolongation. Both drugs have been shown to prolong the QT interval in a concentration-dependent manner. Concomitant use may increase the risk for QT prolongation.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with citalopram due to an increased risk for QT prolongation. Both drugs have been shown to prolong the QT interval in a concentration-dependent manner. Concomitant use may increase the risk for QT prolongation.
    Rifabutin: (Moderate) Citalopram is metabolized by CYP2C19 and CYP3A4. Rifabutin can induce the metabolism of various CYP 450 isoenzymes, including those involved in citalopram metabolism. The possibility of an increase in the clearance of citalopram should be considered if coadministered with rifabutin.
    Rifampin: (Moderate) Citalopram is metabolized by CYP2C19 and CYP3A4. Rifampin can induce the metabolism of various CYP450 isoenzymes, including those involved in citalopram metabolism. Although no clinical data are available to support a clinically significant interaction, citalopram may need to be administered in higher doses in patients chronically taking rifampin.
    Rilpivirine: (Major) Concurrent use of citalopram and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Citalopram also causes dose-dependent QT interval prolongation.
    Risperidone: (Major) Because both citalopram and risperidone are associated with a possible risk for QT prolongation and torsade de pointes (TdP), caution is advisable during concurrent use. Citalopram causes dose-dependent QT interval prolongation and risperidone is associated with a risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended.
    Ritonavir: (Minor) Concurrent use of ritonavir may increase citalopram exposure and treatment-related adverse effects. Ritonavir is a strong CYP3A4 inhibitor. Because CYP3A4 is one of the primary enzymes involved in the metabolism of citalopram, it is expected that strong CYP3A4 inhibitors might decrease the clearance of citalopram. However, coadministration of citalopram and another strong CYP3A4 inhibitor ketoconazole did not significantly affect the pharmacokinetics of citalopram.
    Rivaroxaban: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like rivaroxaban. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
    Rizatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering rizatriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and SSRIs. Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue the SSRI and rizatriptan and initiate symptomatic treatment if serotonin syndrome occurs.
    Romidepsin: (Major) Citalopram causes dose-dependent QT interval prolongation. Romidepsin has been reported to prolong the QT interval. According to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Rucaparib: (Moderate) The maximum daily dose of citalopram in patients receiving concomitant treatment with rucaparib is 20 mg. Monitor for an increase in citalopram-related adverse reactions, including QT prolongation. Citalopram is a CYP2C19 substrate and rucaparib is a weak CYP2C19 inhibitor.
    Safinamide: (Major) The concurrent use of selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) is generally avoided; however, the manufacturer of safinamide recommends monitoring for serotonin syndrome and using the lowest effective dose of the SSRI during concurrent use. During clinical trial evaluation of safinamide, 1 case of serotonin syndrome occurred during co-administration with an SSRI. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Salsalate: (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. A cohort study in > 26,000 patients found that SSRI use alone increased the risk for serious GI bleed by 3.6-fold; when an SSRI was combined with aspirin the risk was increased by > 5-fold. The absolute risk of GI bleed from concomitant therapy with aspirin and a SSRI was low (20/2640 patients) in this cohort study and the clinician may determine that the combined use of these drugs is appropriate.
    Saquinavir: (Major) Concurrent use of citalopram and saquinavir boosted with ritonavir should be avoided if possible due to an increased risk for QT prolongation and torsade de pointes (TdP). If no acceptable alternative therapy is available, specific ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Saquinavir boosted with ritonavir also increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as TdP. In addition, the concurrent use of saquinavir boosted with ritonavir and citalopram or escitalopram should be avoided if possible due to the potential for elevated plasma concentrations of citalopram or escitalopram. Saquinavir boosted with ritonavir is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of citalopram and escitalopram. In addition, citalopram and escitalopram are also metabolized by CYP2D6, an isoenzyme that may be inhibited by ritonavir. Because both citalopram and escitalopram are metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease the clearance of these SSRIs. No clinical studies have been performed; however, caution is advised if citalopram or escitalopram are coadministered with saquinavir/ritonavir.
    Selegiline: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with selective serotonin reuptake inhibitors (SSRIs). MAOIs should not be used within 5 weeks of discontinuing treatment with fluoxetine or within 14 days of discontinuing treatment with other SSRIs. Conversely, SSRIs should not be initiated within 14 days of stopping an MAOI. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Sertraline: (Major) Due to the similarity in pharmacology of sertraline and citalopram and the potential for serious adverse reactions, including serotonin syndrome, these selective serotonin reuptake inhibitors (SSRIs) should not be administered together. Also, both sertraline and citalopram have been associated with QT prolongation and torsade de pointes (TdP), which could theoretically result in additive effects on the QT interval. It is advisable to monitor for signs and symptoms of serotonin syndrome during an overlapping transition from one SSRI to another SSRI.
    Sevoflurane: (Major) Halogenated anesthetics are associated with a risk for QT prolongation. Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Short-acting beta-agonists: (Minor) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with citalopram include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Sibutramine: (Major) Sibutramine is a serotonin reuptake inhibitor. Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering sibutramine with other drugs that have serotonergic properties such as selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. In addition, in vitro studies indicate that metabolism of sibutramine is mediated through CYP3A4. Theoretically, the metabolism of sibutramine may be decreased as a result of CYP3A4 inhibition by fluoxetine or fluvoxamine. Patients receiving sibutramine in combination with an SSRI should be monitored for the emergence of serotonin syndrome, neuroleptic malignant syndrome-like reactions, or other adverse effects.
    Simeprevir: (Moderate) Simeprevir, a mild intestinal CYP3A4 inhibitor, may increase the side effects of citalopram, which is a CYP3A4 substrate. Monitor patients for adverse effects of citalopram, such as QT prolongation, serotonin syndrome, and neuroleptic malignant syndrome.
    Siponimod: (Major) Avoid coadministration of siponimod and citalopram due to the potential for additive QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Citalopram causes dose-dependent QT interval prolongation.
    Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Moderate) Use caution when prescribing sodium picosulfate; magnesium oxide; anhydrous citric acid in patients taking concomitant medications that are known to induce Antidiuretic Hormone Secretion (SIADH), such as tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), antipsychotics and carbamazepine, as these drugs may increase the risk of water retention and/or electrolyte imbalance.
    Solifenacin: (Major) According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval, such as solifenacin, is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined.
    Sorafenib: (Major) Avoid coadministration of citalopram with sorafenib due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct any electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Citalopram causes dose-dependent QT interval prolongation. Sorafenib has also been associated with QT prolongation.
    Sotalol: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Spironolactone: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    St. John's Wort, Hypericum perforatum: (Major) Due to possible additive effects on serotonin concentrations, it is advisable to avoid combinations of St. John's wort, Hypericum perforatum with selective serotonin reuptake inhibitors (SSRIs). Interactions between SSRIs and serotonergic agents can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Several cases of serotonin syndrome reactions have been documented when SSRIs were used concurrently with St. John's wort. A single case report is noted of a 50 year old woman with depression who experienced excessive sedation after ingesting paroxetine with St. John's wort. After discontinuing her conventional paroxetine treatment for 10 days, she started St. John's wort powder at a dose of 600 mg per day. The woman experienced no adverse events related to the change in therapy. She decided to take paroxetine 20 mg one evening due to an episode of insomnia. The next day she was found in an arousable but lethargic and incoherent state. After 2 hours, she complained of weakness, fatigue, and nausea. The patient recovered completely within 48 hours.
    Streptokinase: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with an SSRI.
    Sufentanil: (Moderate) Citalopram impairs metabolism via the CYP2D6 pathway at therapeutic doses. This can result in increased concentrations of drugs metabolized via the same pathway, including some opiate agonists.
    Sumatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sumatriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and SSRIs. Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue the SSRI and sumatriptan and initiate symptomatic treatment if serotonin syndrome occurs.
    Sunitinib: (Major) Coadministration of citalopram with sunitinib is not recommended due to the risk of QT prolongation. If concomitant use is unavoidable, ECG monitoring is recommended. Both drugs can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP).
    Tacrolimus: (Major) Concurrent use of citalopram with tacrolimus is not recommended due to a possible risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Tacrolimus causes QT prolongation. Citalopram causes dose-dependent QT interval prolongation.
    Tamoxifen: (Major) According to the manufacturer of citalopram, concurrent use with other drugs that prolong the QT interval such as tamoxifen is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended; consider also monitoring electrolytes. Citalopram causes dose-dependent QT interval prolongation. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses.
    Tamsulosin: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as citalopram. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Tapentadol: (Major) Caution is advised when tapentadol is coadministered with selective serotonin reuptake inhibitors (SSRIs) as this combination may increase the potential for serotonin syndrome development. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage adjustments (increases) of either agent.
    Tedizolid: (Minor) Caution is warranted with the concurrent use of tedizolid and selective serotonin reuptake inhibitors (SSRIs) due to the theoretical risk of serotonin syndrome. Animal studies did not predict serotonergic effects; however, patients on concurrent SSRIs were excluded from clinical trials. Addtionally, tedizolid is an antibiotic that is also a weak reversible, non-selective MAO inhibitor and monoamine oxidase type A deaminates serotonin; therefore, coadministration theoretically could lead to serious reactions including serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome has been reported in patients receiving either citalopram, escitalopram, fluoxetine, or paroxetine in combination with linezolid, which is structurally similar to tedizolid.
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering citalopram with telaprevir due to an increased potential for citalopram-related adverse events. If citalopram dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of citalopram. Citalopram is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated citalopram plasma concentrations.
    Telavancin: (Major) Concurrent use of citalopram and telavancin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Telavancin has also been associated with QT prolongation.
    Telithromycin: (Major) Concurrent use of telithromycin and citalopram should be avoided if possible. Telithromycin has the potential to prolong the QT interval. Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer of citalopram, ECG monitoring is recommended in patients receiving concurrent drugs that prolong the QT interval. In addition, citalopram concentrations may be increased with concomitant use. Citalopram is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Telmisartan: (Minor) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with telmisartan, a weak CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and citalopram is necessary, as the systemic exposure of citalopram may be decreased resulting in reduced efficacy. If these drugs are used together, monitor patients for suboptimal efficacy of citalopram; consider increasing the dose of citalopram if necessary. Citalopram is partially metabolized by CYP3A4. The mean Cmax and AUC of another sensitive CYP3A4 substrate was decreased by 25% and 48%, respectively, when coadministered with telotristat ethyl; the mechanism of this interaction appears to be that telotristat ethyl increases the glucuronidation of the CYP3A4 substrate.
    Tenecteplase: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with an SSRI.
    Terbinafine: (Moderate) Systemic terbinafine inhibits hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as selective serotonin reuptake inhibitors (SSRIs). The clinical relevance of the interaction is not known. Topical forms of terbinafine do not interact.
    Tetrabenazine: (Major) Citalopram causes dose-dependent QT interval prolongation. Tetrabenazine is associated with a possible risk for QT prolongation and torsade de pointes. According to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Thiethylperazine: (Moderate) Mild CYP2D6 inhibitors, including citalopram, escitalopram, and sertraline have the potential to inhibit the metabolism of phenothiazines; however, a clinically significant interaction between phenothiazines and these SSRIs is not likely.
    Thioridazine: (Severe) Concurrent use of citalopram and thioridazine is contraindicated. Citalopram causes dose-dependent QT interval prolongation and thioridazine is associated with an established risk of QT prolongation and torsade de pointes (TdP). Thioridazine is primarily metabolized through CYP2D6; elevated plasma concentrations of thioridazine are probable when inhibitors of this isoenzyme, such as citalopram, are coadministered. Substantial increases in serum thioridazine concentrations may lead to prolongation of the QTc interval, which is associated with serious ventricular arrhythmias, such as TdP arrhythmias and sudden death. In addition, use of selective serotonin reuptake inhibitors (SSRIs) with drugs that are dopamine antagonists such as thioridazine, may result in serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Thrombin Inhibitors: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and other drugs that affect coagulation like thrombin inhibitors. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
    Thrombolytic Agents: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with an SSRI.
    Ticagrelor: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving prasugrel. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
    Ticlopidine: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with ticlopidine, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors. In addition, platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., ticlopidine). Patients should be instructed to monitor for signs and symptoms of citalopram-related adverse events and bleeding while taking an SSRI concurrently with ticlopidine and to promptly report any bleeding events to the practitioner.
    Timolol: (Minor) Citalopram mildly inhibits the hepatic CYP2D6 isoenzyme at therapeutic doses. This can result in increased concentrations of drugs metabolized via the same pathway, including timolol.
    Tinzaparin: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like low molecular weight heparins. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
    Tipranavir: (Major) CYP3A4 is involved in the metabolism of citalpram. Anti-retroviral protease inhibitors may increase plasma concentrations of citalopram through CYP3A4 inhibition. Because citalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease citalopram clearance.
    Tirofiban: (Moderate) Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding.
    Tolterodine: (Major) Concurrent use of citalopram and tolterodine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Tolterodine has also been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. In addition, citalopram may inhibit the CYP2D6 metabolism of tolterodine in extensive metabolizers.
    Topiramate: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with topiramate, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors. In addition, concurrent use of topiramate and drugs that affect platelet function such as selective serotonin reuptake inhibitors (SSRIs) may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation.
    Toremifene: (Major) Avoid coadministration of citalopram with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Citalopram also causes dose-dependent QT interval prolongation.
    Torsemide: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Tramadol: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like tramadol with serotonergic drugs, such as citalopram. Several cases of serotonin syndrome have been reported after the administration of tramadol with an SSRI. Post-marketing reports implicate the concurrent use of SSRIs with tramadol in some cases of seizures. Lastly, citalopram is a weak inhibitor of CYP2D6. The analgesic activity of tramadol is due to the activity of both the parent drug and the O-desmethyltramadol metabolite (M1), and M1 formation is dependent on CYP2D6. Therefore, use of tramadol with a CYP2D6-inhibitor may alter tramadol efficacy. In addition, inhibition of CYP2D6 metabolism is expected to result in reduced metabolic clearance of tramadol. This in turn may increase the risk of tramadol-related adverse events including serotonin syndrome and seizures. If serotonin syndrome is suspected, citalopram and concurrent serotonergic agents should be discontinued.
    Trandolapril; Verapamil: (Moderate) During concurrent use of citalopram and verapamil, clinicians should monitor patients for a potential increase in side effects or toxicity. In theory, verapamil may inhibit the metabolism of citalopram through inhibition of CYP3A4. It should be noted that because citalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease citalopram clearance.
    Tranylcypromine: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with selective serotonin reuptake inhibitors (SSRIs). MAOIs should not be used within 5 weeks of discontinuing treatment with fluoxetine or within 14 days of discontinuing treatment with other SSRIs. Conversely, SSRIs should not be initiated within 14 days of stopping an MAOI. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Trazodone: (Major) Avoid coadministration of trazodone and citalopram due to the potential for QT prolongation. If concurrent therapy is considered essential, ECG monitoring is recommended. Concurrent use also increases the risk of serotonin syndrome. Serotonin syndrome has been reported with both drugs when taken alone, but especially when coadministered with other serotonergic agents. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue citalopram and trazodone and initiate symptomatic treatment if serotonin syndrome occurs.
    Triamcinolone: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Triamterene: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Trifluoperazine: (Minor) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Trifluoperazine is associated with a possible risk for QT prolongation.
    Trimipramine: (Major) Citalopram causes dose-dependent QT interval prolongation and tricyclic antidepressants are associated with a possible risk of QT prolongation and torsade de pointes (TdP). According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. In addition, because of the potential risk and severity of serotonin syndrome, caution should be observed when administering citalopram with other drugs that have serotonergic properties such as tricyclic antidepressants. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Clinicians should also be alert for pharmacokinetic interactions between tricyclic antidepressants (TCAs) and SSRIs. Citalopram is a weak inhibitor of CYP2D6, the isoenzyme responsible for metabolism of many of the tricyclic antidepressants. Coadministration of citalopram and imipramine did not significantly affect the plasma concentrations of either drug. However, the concentration of desipramine, the primary metabolite of imipramine, was increased by 50%. The clinical significance of the elevation in desipramine concentration is unknown. However, symptoms of toxicity, including seizures, have been reported when drugs from these 2 classes were used together. A decreased dosage of the TCA or the avoidance of concomitant SSRI therapy should be considered.
    Triptorelin: (Major) Coadministration of citalopram with triptorelin is not recommended due to the risk of QT prolongation. If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
    Urokinase: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with an SSRI.
    Valerian, Valeriana officinalis: (Moderate) Substances that act on the CNS, including psychoactive drugs, may theoretically interact with valerian, Valeriana officinalis. These interactions are probably pharmacodynamic in nature, or result from additive mechanisms of action. Persons taking medications such as SSRIs should discuss the use of herbal supplements with their health care professional prior to consuming these herbs. Patients should not abruptly stop taking their prescribed psychoactive medication.
    Valproic Acid, Divalproex Sodium: (Minor) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with valproic acid, a weak CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
    Vandetanib: (Major) Coadministration of vandetanib with citalopram is not recommended due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Both drugs can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib.
    Vardenafil: (Major) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with citalopram include vardenafil. Therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil produces an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction).
    Vasopressin, ADH: (Minor) Additive hyponatremic effects may be seen in patients treated with vasopressin and drugs associated with water intoxication, hyponatremia, or SIADH including SSRIs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia, which may include monitoring serum sodium or electrolytes periodically. Ensure the patient is compliant with fluid restrictions and intake.
    Vemurafenib: (Major) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with citalopram include vemurafenib. In addition, vemurafenib is an inducer of CYP3A4 and decreased plasma concentrations of drugs metabolized by this enzyme, such as citalopram, could be expected with concurrent use. Use caution, and monitor therapeutic effects of citalopram when coadministered with vemurafenib.
    Venlafaxine: (Major) Due to similarity of pharmacology and the potential for additive adverse effects, including serotonin syndrome, selective serotonin reuptake inhibitors (SSRIs) should generally not be administered with serotonin norepinephrine reuptake inhibitors like venlafaxine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome is suspected, venlafaxine and concurrent serotonergic agents should be discontinued. In addition, venlafaxine and SSRIs including fluoxetine, citalopram, and escitalopram are associated with a possible risk of QT prolongation and torsade de pointes (TdP) and combination therapy should be avoided if possible.
    Verapamil: (Moderate) During concurrent use of citalopram and verapamil, clinicians should monitor patients for a potential increase in side effects or toxicity. In theory, verapamil may inhibit the metabolism of citalopram through inhibition of CYP3A4. It should be noted that because citalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease citalopram clearance.
    Vilazodone: (Major) Due to the potential for serotonin syndrome, caution is advisable when combining selective serotonin reuptake inhibitors (SSRIs) such as citalopram with vilazodone. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients receiving vilazodone and citalopram should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. If serotonin syndrome occurs, all serotonergic agents should be discontinued and supportive symptomatic treatment should be initiated.
    Vorapaxar: (Moderate) Because vorapaxar inhibits platelet aggregation, a potential additive risk for bleeding exists if vorapaxar is given in combination with other agents that affect hemostasis such as selective serotonin reuptake inhibitors (SSRIs). Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion. In addition, fluoxetine and fluvoxamine are CYP3A4 inhibitors and coadministration with vorapaxar, a CYP3A4 substrate, may result in increased serum concentrations of vorapaxar. Increased exposure to vorapaxar may increase the risk of bleeding complications. Patients should be instructed to monitor for signs and symptoms of bleeding while taking a SSRI with vorapaxar and to promptly report any bleeding events.
    Voriconazole: (Major) Avoid coadministration of citalopram and voriconazole due to the potential for additive effects on the QT interval; increased exposure to citalopram is also possible. Both drugs have been associated with QT prolongation; voriconazole has also been associated with rare cases of torsades de pointes, cardiac arrest, and sudden death. If concurrent therapy is considered essential, ECG monitoring is recommended; do not exceed 20 mg per day of citalopram. Voriconazole theoretically might impair the metabolism of citalopram through inhibition of CYP2C19 and CYP3A4. Closely monitor for prolongation of the QT interval and other adverse effects such as drowsiness, fatigue, dry mouth, nausea, or insomnia. Rigorous attempts to correct any electrolyte abnormalities (i.e., potassium, magnesium, calcium) should be made before initiating concurrent therapy.
    Vorinostat: (Major) Citalopram causes dose-dependent QT interval prolongation. Vorinostat is associated with a possible risk for QT prolongation and torsade de pointes. According to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Vortioxetine: (Major) Due to similarity of pharmacology and the potential for additive adverse effects, including serotonin syndrome, vortioxetine should generally not be co-administered with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Warfarin: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of citalopram and warfarin. Carefully monitor patients receiving warfarin therapy if citalopram is initiated or discontinued. Although citalopram does not affect the pharmacokinetics of warfarin, prothrombin time was increased by 5%; the clinical significance is unknown. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
    Ziprasidone: (Major) Concomitant use of ziprasidone and citalopram should be avoided due to the potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer of citalopram, citalopram should not be used in patients who are taking other drugs that prolong the QTc interval. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Zolmitriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering zolmitriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and SSRIs. Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue the SSRI and zolmitriptan and initiate symptomatic treatment if serotonin syndrome occurs.
    Zolpidem: (Moderate) Disorientation, delusions, or hallucinations have been reported rarely during co-administration of zolpidem and SSRIs (e.g., fluoxetine, sertraline, fluvoxamine). The duration of the visual hallucinations has ranged from 30 minutes to 7 hours. Data from a clinical study in which SSRI-treated patients were given immediate-release zolpidem revealed that four of the seven discontinuations during double-blind treatment with zolpidem (n = 95) were associated with impaired concentration, continuing or aggravated depression, and manic reaction. The mechanism for the interaction is thought to be pharmacodynamic in nature; therefore, a similar reaction is possible with other SSRIs such as citalopram.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate and well-controlled studies in pregnant women; citalopram should be used in pregnancy only when the benefits to the mother outweigh the potential risk to the fetus. There is some evidence that SSRI use may cause non-teratogenic fetal harm during human pregnancy. Neonates exposed to citalopram and other SSRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Symptoms have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of serotonergic agents or, possibly, a neonatal abstinence syndrome. Epidemiologic reports also suggest a possible association between maternal use of SSRIs after 20 weeks gestation and the development of persistent pulmonary hypertension (PPHN) of the newborn. More recent retrospective studies have not shown an increased risk of PPHN with SSRI exposure. In December 2011, the FDA issued a safety announcement stating that based on conflicting data an increased risk of PPHN from SSRI exposure cannot be determined, and that healthcare professionals should not alter their current practice of treating depression in pregnancy at this time. Women who are pregnant, or are planning a pregnancy, and currently taking citalopram should consult with their physician about whether to continue taking it. When treating a pregnant woman with an SSRI or other serotonergic agent during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. If clinically feasible, gradual tapering of the medication prior to delivery may be considered. A prospective study of pregnant women receiving antidepressant treatment found that only 26% of those maintained on their antidepressant had relapsed versus 68% of those who had discontinued their medication. Increasing evidence suggests an association between antidepressant use during pregnancy and a subsequent diagnosis of autism spectrum disorder (ASD) in the offspring. In 2 separate population based case-control studies, an approximate 2-fold increased risk of autism spectrum disorder was observed. One study found the increased risk was associated only with SSRI use, while the other study found an increased risk associated with use of SSRIs and tricyclic antidepressants. In animal studies, citalopram has been shown to have adverse effects on embryo/fetal and postnatal development, including teratogenic effects, when administered at doses greater than human maximum therapeutic doses. In general, animal studies have shown that SSRIs downregulate the serotonin receptors in the fetal cortex and that these changes can be present for a period of time after birth. The effect of citalopram on labor and delivery is unknown. The National Pregnancy Registry for Psychiatric Medications is dedicated to evaluating the safety of psychiatric medications that may be taken by women during pregnancy to treat a wide range of mood, anxiety, or psychiatric disorders. The primary goal of this Registry is to determine the frequency of major malformations, such as heart defects, cleft lip, or neural tube defects, in babies exposed to various psychiatric drugs during pregnancy. While the research concentrates on atypical antipsychotics and antidepressant use, pregnant women using other psychiatric medications are encouraged to register. For more information, contact the registry at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry or by phone 1-866-961-2388.

    MECHANISM OF ACTION

    The precise antidepressant effect of SSRIs is not fully understood, but involves selective serotonin reuptake blockade at the neuronal membrane, which enhances the actions of serotonin (5-HT). Initially, SSRIs increase availability of serotonin in the somatodendritic area through serotonin reuptake blockade at the serotonin transport pump. During long-term administration of SSRIs, serotonin autoreceptors are down-regulated and desensitized, allowing the neuron to increase serotonin release in the axon terminal synapses and increase its neuronal impulses. Because of the delay in therapeutic response to SSRIs, it is theorized that the change in the balance of serotonin receptors over time is an important mechanism of effect. The therapeutic action of SSRIs in treating anxiety disorders is thought to occur from potent central serotonin reuptake blockade, although the exact mechanism is unknown. SSRIs have less sedative, anticholinergic, and cardiovascular effects than do tricyclic antidepressants due to dramatically decreased binding to histaminergic, muscarinic, and alpha-adrenergic receptors. However, unlike other SSRIs, citalopram is associated with a known risk of QT prolongation.

    PHARMACOKINETICS

    Citalopram is administered orally. It exhibits linear and dose-proportional pharmacokinetics over the therapeutic dosage range. Protein binding of citalopram and its metabolites are about 80%. In humans, unchanged citalopram is the predominant compound in plasma. The parent drug is metabolized via N-demethylation primarily by the CYP3A4 and CYP2C19 isoenzymes. In vitro studies show that citalopram is at least 8 times more potent than its metabolites in the inhibition of serotonin reuptake, suggesting that the metabolites evaluated do not likely contribute significantly to the antidepressant actions of citalopram. Only 20% of the systemic clearance is due to renal clearance; renal elimination is a minor route of elimination. The citalopram half-life in a healthy individual is 35 hours.
     
    Affected Cytochrome P450 (CYP450) enzymes: CYP2C19, CYP1A2, CYP2D6
    In vitro, citalopram is a mild inhibitor of CYP1A2, CYP2D6, and CYP2C19. Based on in vitro studies, citalopram does not appear to inhibit other isoenzymes (e.g., 3A4, 2C9, or 2E1) to any clinically significant degree. In an evaluation of CYP2C19 poor metabolizers, citalopram steady-state Cmax and AUC were increased by 68% and 107%, respectively. Steady-state levels were not significantly different in poor metabolizers and extensive metabolizers of CYP2D6. Due to dose-dependent QT prolongation, a lower maximum daily dosage is recommended in patients who are poor metabolizers of CYP2C19 or receiving a CYP2C19 inhibitor.

    Oral Route

    The absolute bioavailability of citalopram following a single oral dose is about 80% and is not affected by the presence of food. The tablet and oral solution formulations are bioequivalent. Peak plasma concentrations are attained about 4 hours after dosing. Steady state plasma concentrations are achieved within approximately one week and are expected to be 2.5 times the plasma concentrations observed after a single dose.