PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    First Generation Antipsychotics

    BOXED WARNING

    Angina, apheresis, AV block, bradycardia, cardiac arrhythmias, cardiomyopathy, celiac disease, cerebrovascular disease, females, fever, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypotension, hypothyroidism, hypovolemia, long QT syndrome, myocardial infarction, orthostatic hypotension, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, systemic lupus erythematosus (SLE), torsade de pointes

    Thioridazine is contraindicated in patients with QT prolongation due to congenital long QT syndrome or a history of cardiac arrhythmias. Hypertensive or hypotensive heart disease of extreme degree is also a contraindication to thioridazine administration. Some phenothiazines, such as thioridazine, have an established risk of QT prolongation, torsade de pointes (TdP), and sudden death, and should not be used in individuals with known cardiac conduction defects (e.g., AV block, bundle-branch block). Medications known to prolong the QT interval are contraindicated use with thioridazine, as coadministration could lead to TdP. Concurrent use of thioridazine with agents which are CYP2D6 inhibitors may also increase the risk of TdP. Hypotension, syncope, angina, tachycardia, cardiac arrhythmias, or QT prolongation may be associated with aggressive dose titration. If thioridazine is administered to patients with cardiac disease, a low initial dosage should be used, followed by gradual dosage titration. A baseline ECG and a measurement of serum potassium should be performed in all patients prior to treatment with thioridazine. Use thioridazine with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, heart failure, stress-related cardiomyopathy, myocardial infarction, cerebrovascular disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to cause electrolyte imbalances. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, abnormally low body temperature, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation. Because the cardiotoxic effects are dose-related, patients should be instructed to strictly adhere to the prescribed dosage. Instruct patients to report palpitations, irregular heartbeat, or syncope to their prescriber for further evaluation. Low potency phenothiazines such as thioridazine can cause orthostatic hypotension due to their potent alpha-1 receptor blocking effects. Phenothiazines may potentiate hypotension caused by hypovolemia, the presence of antihypertensive drugs, or a dehydrated state. Orthostatic hypotension could lead to falls with the potential for fractures and other injuries. Complete a fall risk assessment upon antipsychotic initiation in patients with conditions, diseases, or taking concurrent medications that could exacerbate orthostasis and recurrently during long-term therapy in at-risk patients.

    Dementia, geriatric, stroke

    Geriatric patients may be more susceptible to the actions and adverse effects of phenothiazines, including tardive dyskinesia, dystonias, orthostatic hypotension, QT prolongation, anticholinergic effects, and risk for falls and fractures. Initiate treatment with lower doses followed by careful dosage titration and close monitoring. Antipsychotics are not approved for the treatment of dementia-related psychosis in geriatric patients and the use of phenothiazines in this population should be avoided if possible due to an increase in morbidity and mortality in elderly patients with dementia receiving antipsychotics. Deaths have typically resulted from heart failure, sudden death, or infections. An increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatal events, has also been reported. The Beers Criteria consider antipsychotics to be potentially inappropriate medications (PIMs) in elderly patients and should be avoided except for treating schizophrenia, bipolar disorder, or short-term antiemetic use during chemotherapy. The Beers panel recommends avoiding thioridazine in geriatric patients with delirium, dementia, lower urinary tract symptoms/benign prostatic hyperplasia in men, syncope, or Parkinson's disease. Non-pharmacological strategies are first-line options for treating delirium- or dementia-related behavioral problems unless they have failed or are not possible and the patient is a substantial threat to self or others. If antipsychotic use is necessary in geriatrics with a history of falls or fractures, consider reducing the use of other CNS depressants and implement other fall risk strategies. Due to the potential for antipsychotic-induced hyponatremia and SIADH, sodium levels should be closely monitored when thioridazine is initiated and after dose changes. According to the federal Omnibus Budget Reconciliation Act (OBRA) regulations in residents of long-term care facilities, antipsychotic therapy should only be initiated in a patient with behavioral or psychological symptoms of dementia (BPSD) when the patient is a danger to self or others or has symptoms due to mania or psychosis. For acute conditions persisting beyond 7 days, appropriate non-pharmacologic interventions must be attempted, unless clinically contraindicated and documented. OBRA provides general dosing guidance for antipsychotic treatment of BPSD. Antipsychotics are subject to periodic review for effectiveness, medical necessity, gradual dose reduction (GDR), or rationale for continued use. Refer to the OBRA guidelines for complete information.

    DEA CLASS

    Rx

    DESCRIPTION

    Oral low potency phenothiazine antipsychotic
    Risk of QT prolongation and torsade de pointes (TdP) limits use to refractory schizophrenic patients
    As with all antipsychotics, boxed warning for increased mortality risk in elderly patients with dementia-related psychosis

    COMMON BRAND NAMES

    Mellaril

    HOW SUPPLIED

    Mellaril/Thioridazine/Thioridazine Hydrochloride Oral Tab: 10mg, 25mg, 50mg, 100mg

    DOSAGE & INDICATIONS

    For the treatment of schizophrenia in patients who fail to respond adequately to treatment with other antipsychotics.
    Oral dosage
    Adults

    Initially, 50 to 100 mg PO 3 times per day depending on the severity of symptoms. Because geriatric patients may be more sensitive to side effects (e.g., anticholinergic effects, orthostatic hypotension), a low initial dose and slower titration are advisable. Titrate gradually to a total daily dose ranging from 200 to 800 mg/day based on response and tolerability. Once effective control of symptoms has been achieved, the dose should be reduced to the lowest effective dose for maintenance therapy. Max: 800 mg/day. Due to the risk of significant, potentially life-threatening arrhythmias, thioridazine should be used only in patients who have failed to respond adequately to treatment with other antipsychotics or have intolerable adverse effects from those drugs. It is strongly recommended that a patient be given at least 2 trials, each with a different antipsychotic, at an adequate dose, and for an adequate duration before initiating therapy with thioridazine. Thioridazine has not been systematically evaluated in the treatment of refractory schizophrenia, and its efficacy in such patients is unknown.

    Adolescents

    Initially, 0.5 mg/kg/day given orally in divided doses. The dosage may be increased gradually until the optimal therapeutic effect is obtained, using the lowest effective dose. Max: 3 mg/kg/day. Due to the risk of significant, potentially life-threatening arrhythmias, thioridazine should be used only in patients who have failed to respond adequately to treatment with other antipsychotics or have intolerable adverse effects from those drugs. It is strongly recommended that a patient be given at least 2 trials, each with a different antipsychotic, at an adequate dose, and for an adequate duration before initiating therapy with thioridazine. Thioridazine has not been systematically evaluated in the treatment of refractory schizophrenia, and its efficacy in such patients is unknown.

    For the treatment of severe behavioral or psychological symptoms of dementia† (BPSD)†.
    Oral dosage
    Geriatric Adults

    Initially, 10 to 25 mg PO 2 to 3 times per day. May gradually increase at weekly intervals, as needed and tolerated. The dosage may range from 20 to 200 mg/day PO. Due to the risk of significant, potentially life-threatening arrhythmias, thioridazine should be used only in patients who have failed to respond adequately to other antipsychotics or who have intolerable adverse effects from those drugs. Antipsychotics are not FDA-approved for this indication and the labeling of all antipsychotics contains a boxed warning noting an increased risk of death in geriatric patients being treated for behavioral problems associated with dementia. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of antipsychotics in long-term care facility (LTCF) residents with dementia-related behavioral symptoms. According to the OBRA guidelines, the use of thioridazine should be avoided due to the boxed warning regarding QT prolongation. OBRA Max: 75 mg/day PO if treatment is medically necessary, except when documentation is provided showing that higher doses are necessary to maintain or improve the resident's functional status. In addition, the facility must attempt a gradual dose reduction (GDR) in 2 separate quarters, at least 1 month apart, within the first year of admission to the facility or after the facility has initiated an antipsychotic, unless clinically contraindicated. After the first year, a GDR must be attempted annually unless clinically contraindicated. The GDR may be considered clinically contraindicated if the target symptoms returned or worsened after the most recent GDR attempt within the facility and the physician has documented justification for why attempting additional dose reductions at that time would likely impair the resident's function or increase distressed behavior.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    800 mg/day PO.

    Geriatric

    800 mg/day PO. Debilitated patients require lower dosages.

    Adolescents

    3 mg/kg/day PO.

    Children

    Safety and efficacy have not been established.

    Infants

    Not indicated.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    In general, phenothiazines are contraindicated in patients with significant hepatic impairment.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. Thioridazine is not removed by hemodialysis.

    ADMINISTRATION

    Oral Administration

    May take with or without food. If stomach upset or nausea occur, take with food.

    Oral Liquid Formulations

    Oral concentrate: Administer using a calibrated measuring device. Dilute immediately prior to administration with 60 to 120 mL of fruit juice, distilled water, or acidified tap water. Avoid spilling the solution on the skin and clothing.
    Oral suspension: Shake well prior to administration. Administer using a calibrated measuring device.

    STORAGE

    Mellaril:
    - Protect from light
    - Store at room temperature (between 59 to 86 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Phenothiazine hypersensitivity

    Thioridazine should be avoided in patients with known hypersensitivity to thioridazine. Cross-sensitivity may occur in patients with a phenothiazine hypersensitivity to other similar compounds.

    Agranulocytosis, bone marrow suppression, hematological disease, infection, leukopenia, neutropenia

    Thioridazine should be used with caution in patients with hematological disease. Hematologic effects including leukopenia, neutropenia, and agranulocytosis have been associated with antipsychotic use. A history of drug-induced leukopenia or neutropenia or pre-existing low white blood cell (WBC) count may increase the likelihood of developing hematologic effects during treatment with an antipsychotic medication. Patients with a history of clinically significant low WBC count or drug-induced leukopenia/neutropenia should have frequent complete blood count (CBC) assessments during the first few months of treatment. Discontinuation of the antipsychotic should be considered if a clinically significant decline in WBC occurs in the absence of an identifiable cause. Patients with clinically significant neutropenia should be closely monitored for pyrexia or elevated body temperature and infection, and appropriate medical intervention should be instituted if necessary. Thioridazine should be discontinued in patients with severe neutropenia (ANC less than 1000/mm3); ongoing medical care is recommended until the symptoms resolve. Patients with bone marrow suppression secondary to phenothiazine use should not be re-exposed to phenothiazine treatment.

    CNS depression, coadministration with other CNS depressants, coma, driving or operating machinery, ethanol ingestion, head trauma

    Thioridazine is contraindicated for use in patients in comatose states (i.e., coma) or with severe CNS depression (e.g., acute head trauma) from any cause. The phenothiazines may have deleterious effects on neuronal recovery after acute brain injuries. In addition, brain-injured patients are more susceptible to adverse CNS effects of the phenothiazines. Because thioridazine may impair mental and/or physical abilities, all patients should be cautioned against driving or operating machinery, or performing other tasks requiring mental alertness, until they are aware of how the medication affects them. Somnolence could lead to falls with the potential for fractures and other injuries. A fall risk assessment should be completed when initiating an antipsychotic in patients with conditions, diseases, or concurrent medication use that could exacerbate somnolence. A fall risk assessment should be completed recurrently in at-risk patients on long-term antipsychotic therapy. Given the primary CNS effects of phenothiazine antipsychotics, caution should be used during coadministration with other CNS depressants and alcohol. Ethanol ingestion may further impair cognitive and motor skills and patients should be advised to avoid use of alcoholic beverages.

    Dental work, surgery

    Thioridazine is contraindicated in patients with drug-induced CNS depression. Phenothiazines may prolong and intensify the sedative actions of CNS depressant medications (e.g., anesthetics, barbiturates, ethanol, hypnotics, and opiates). Thioridazine should be used cautiously during dental work, surgery, and other procedures where the use of CNS depressant medications is common.

    Intracranial mass, seizure disorder, seizures

    Phenothiazines may lower the seizure threshold. Patients who have a history of seizure disorder, epilepsy, or EEG abnormalities should be carefully monitored during therapy with thioridazine. Phenothiazines do not intensify the anticonvulsant effects of the barbiturates or other anticonvulsants; patients with seizures who are on anticonvulsants should not have their anticonvulsant dosages reduced. Patients with a pre-existing intracranial mass may be more susceptible to seizures if phenothiazines are administered. The continuation of adequate anticonvulsant therapy should prevent an increase in seizure frequency during phenothiazine treatment. If thioridazine therapy is needed, it should be initiated with a low dosage and titrated upward slowly to desired clinical effect. Abrupt increases in phenothiazine dosage should be avoided.

    Tardive dyskinesia

    Tardive dyskinesia is a syndrome of potentially irreversible, involuntary, dyskinetic movements that may develop in patients treated with antipsychotics. Regular evaluation for movement disorders is recommended (e.g., AIMS, DISCUS). Factors associated with a greater susceptibility to tardive dyskinesia include an age above 55 years, female gender, white or African ethnicity, presence of a mood disorder, intellectual disability, CNS injury, prior or current akathisia, significant parkinsonism, or acute dystonic reaction. The rate of tardive dyskinesia in adults treated with a first generation antipsychotic appears to be at least 3 times that observed with second generation antipsychotics. The risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotics administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief periods at low doses or may arise after drug discontinuation. Antipsychotics may suppress the signs and symptoms of tardive dyskinesia and thereby mask the underlying process; however, the syndrome may also remit partially or completely if the antipsychotic is withdrawn. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown. If signs and symptoms of tardive dyskinesia appear, thioridazine discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome.

    Anticholinergic medications, closed-angle glaucoma, ileus, prostatic hypertrophy, urinary retention

    Thioridazine should be used with caution in patients with prostatic hypertrophy, closed-angle glaucoma, paralytic ileus, or urinary retention because the drug exhibits anticholinergic activity that can exacerbate these conditions. The anticholinergic effects of the phenothiazines may be additive to other anticholinergic medications.

    Angina, apheresis, AV block, bradycardia, cardiac arrhythmias, cardiomyopathy, celiac disease, cerebrovascular disease, females, fever, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypotension, hypothyroidism, hypovolemia, long QT syndrome, myocardial infarction, orthostatic hypotension, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, systemic lupus erythematosus (SLE), torsade de pointes

    Thioridazine is contraindicated in patients with QT prolongation due to congenital long QT syndrome or a history of cardiac arrhythmias. Hypertensive or hypotensive heart disease of extreme degree is also a contraindication to thioridazine administration. Some phenothiazines, such as thioridazine, have an established risk of QT prolongation, torsade de pointes (TdP), and sudden death, and should not be used in individuals with known cardiac conduction defects (e.g., AV block, bundle-branch block). Medications known to prolong the QT interval are contraindicated use with thioridazine, as coadministration could lead to TdP. Concurrent use of thioridazine with agents which are CYP2D6 inhibitors may also increase the risk of TdP. Hypotension, syncope, angina, tachycardia, cardiac arrhythmias, or QT prolongation may be associated with aggressive dose titration. If thioridazine is administered to patients with cardiac disease, a low initial dosage should be used, followed by gradual dosage titration. A baseline ECG and a measurement of serum potassium should be performed in all patients prior to treatment with thioridazine. Use thioridazine with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, heart failure, stress-related cardiomyopathy, myocardial infarction, cerebrovascular disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to cause electrolyte imbalances. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, abnormally low body temperature, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation. Because the cardiotoxic effects are dose-related, patients should be instructed to strictly adhere to the prescribed dosage. Instruct patients to report palpitations, irregular heartbeat, or syncope to their prescriber for further evaluation. Low potency phenothiazines such as thioridazine can cause orthostatic hypotension due to their potent alpha-1 receptor blocking effects. Phenothiazines may potentiate hypotension caused by hypovolemia, the presence of antihypertensive drugs, or a dehydrated state. Orthostatic hypotension could lead to falls with the potential for fractures and other injuries. Complete a fall risk assessment upon antipsychotic initiation in patients with conditions, diseases, or taking concurrent medications that could exacerbate orthostasis and recurrently during long-term therapy in at-risk patients.

    Pulmonary disease

    Thioridazine should be used cautiously in patients with significant pulmonary disease. Serious respiratory events have been reported with phenothiazine therapy, including respiratory arrest. If thioridazine is administered to patients with severe chronic pulmonary disease, a low initial dosage should be used, followed by gradual dosage titration. Respiratory depression, apnea, or pulmonary edema may occur, particularly in the setting of overdose.

    Children, infants, neonates, Reye's syndrome

    Due to the risk and severity of potential adverse effects, thioridazine should be reserved for pediatric patients who are unresponsive to other agents. Thioridazine should not be used to treat conditions in children for which specific pediatric dosages have not been established. Children with acute illnesses (e.g., varicella-zoster infections, CNS infections, measles, gastroenteritis, or in a dehydrated state) may be more susceptible to developing adverse reactions, respiratory depression, and extrapyramidal symptoms from the phenothiazines. Children may also be more susceptible to the cardiac effects of the phenothiazines, particularly if there is a known history of congenital long QT syndrome. Therefore, thioridazine is contraindicated in patients with QT prolongation due to congenital long QT syndrome or a history of cardiac arrhythmias. Routine cardiovascular monitoring has been suggested for children receiving phenothiazines due to the potential of these agents to produce adverse cardiac effects. Phenothiazines should not be administered to children or adolescents whose signs and symptoms are suggestive of Reye's syndrome. There is no known indication for use of thioridazine in infants or neonates. In addition, adverse effects such as extrapyramidal effects, agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported after delivery in neonates and infants exposed to antipsychotics during the third trimester. These effects have varied in severity ranging from self-limited to requiring intensive care unit stays and prolonged hospitalization.

    Encephalopathy, hepatic disease, jaundice

    Phenothiazines, such as thioridazine, should be used cautiously in patients with hepatic disease. Patients with hepatic disease may have decreased hepatic metabolism of these drugs. Patients with a history of jaundice secondary to phenothiazine use should not be re-exposed to phenothiazine treatment. Patients with a history of hepatic encephalopathy secondary to cirrhosis have increased CNS sensitivity (e.g., decreased cerebration, EEG-wave slowing) to the phenothiazines.

    Neurological disease, Parkinson's disease

    Antipsychotics can cause motor and sensory instability, which may lead to falls with the potential for fractures and other injuries. A fall risk assessment should be completed when initiating an antipsychotic in patients with diseases (e.g., neurological disease), conditions, or concurrent medication use that could exacerbate motor and sensory instability. A fall risk assessment should be completed recurrently in at-risk patients on long-term antipsychotic therapy. Phenothiazines, like thioridazine, should be used cautiously in patients with Parkinson's disease. Central blockade of dopamine (D2) receptors by phenothiazines may dramatically worsen the extrapyramidal symptoms of Parkinson's disease.

    Dementia, geriatric, stroke

    Geriatric patients may be more susceptible to the actions and adverse effects of phenothiazines, including tardive dyskinesia, dystonias, orthostatic hypotension, QT prolongation, anticholinergic effects, and risk for falls and fractures. Initiate treatment with lower doses followed by careful dosage titration and close monitoring. Antipsychotics are not approved for the treatment of dementia-related psychosis in geriatric patients and the use of phenothiazines in this population should be avoided if possible due to an increase in morbidity and mortality in elderly patients with dementia receiving antipsychotics. Deaths have typically resulted from heart failure, sudden death, or infections. An increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatal events, has also been reported. The Beers Criteria consider antipsychotics to be potentially inappropriate medications (PIMs) in elderly patients and should be avoided except for treating schizophrenia, bipolar disorder, or short-term antiemetic use during chemotherapy. The Beers panel recommends avoiding thioridazine in geriatric patients with delirium, dementia, lower urinary tract symptoms/benign prostatic hyperplasia in men, syncope, or Parkinson's disease. Non-pharmacological strategies are first-line options for treating delirium- or dementia-related behavioral problems unless they have failed or are not possible and the patient is a substantial threat to self or others. If antipsychotic use is necessary in geriatrics with a history of falls or fractures, consider reducing the use of other CNS depressants and implement other fall risk strategies. Due to the potential for antipsychotic-induced hyponatremia and SIADH, sodium levels should be closely monitored when thioridazine is initiated and after dose changes. According to the federal Omnibus Budget Reconciliation Act (OBRA) regulations in residents of long-term care facilities, antipsychotic therapy should only be initiated in a patient with behavioral or psychological symptoms of dementia (BPSD) when the patient is a danger to self or others or has symptoms due to mania or psychosis. For acute conditions persisting beyond 7 days, appropriate non-pharmacologic interventions must be attempted, unless clinically contraindicated and documented. OBRA provides general dosing guidance for antipsychotic treatment of BPSD. Antipsychotics are subject to periodic review for effectiveness, medical necessity, gradual dose reduction (GDR), or rationale for continued use. Refer to the OBRA guidelines for complete information.

    Sunlight (UV) exposure

    Photosensitivity may occur with the use of phenothiazines; patients should avoid undue sunlight (UV) exposure and the use of tanning beds during treatment with thioridazine; patients should follow accepted UV-protective practices when exposed.

    Accidental exposure

    Oral solutions of phenothiazines should not come in contact with the skin. Although rare, contact dermatitis has been reported with accidental exposure to phenothiazines. The use of latex gloves has been recommended when administering the oral liquid forms of thioridazine.

    Abrupt discontinuation

    Phenothiazines, like thioridazine, do not cause physical or psychological dependence. However, abrupt discontinuation of phenothiazines can produce nausea, dizziness, and trembling. These effects are only temporary, and can be reduced by a gradual reduction in dosage, or continuation of concomitant antiparkinsonian agents for several weeks after the phenothiazine is withdrawn.

    Renal failure

    Phenothiazines, like thioridazine, are not successfully removed by hemodialysis due to their high-protein binding in the serum (90% or more protein bound). Use with caution in patients with renal failure.

    Ocular disease

    Phenothiazines, like thioridazine, may cause various forms of ocular disease. All patients should be closely monitored for changes in visual acuity and corneal deposits. Routine periodic ophthalmologic exams are recommended.

    Chemotherapy, GI obstruction, vomiting

    The antiemetic activity of phenothiazines may mask the signs and symptoms (i.e., vomiting) or the diagnosis of certain medical conditions (i.e., GI obstruction, ileus). Likewise, the symptoms of certain medication toxicities (i.e., vomiting due to chemotherapy; ototoxicity of aminoglycosides) may be masked. Phenothiazines, such as thioridazine, should be used cautiously in these patients.

    Tobacco smoking

    There is some evidence to suggest that patients who smoke large amounts of cigarettes (i.e., 20 or more per day) may have increased metabolism of the phenothiazines like thioridazine. Clinicians should be aware that increased dosage requirements may occur in some tobacco smokers. Conversely, if patients stop tobacco smoking, the dosage of the phenothiazine may need to be reduced.

    Labor, obstetric delivery, pregnancy, pregnancy testing

    No well-controlled data are available to determine the safety and efficacy of thioridazine during human pregnancy; therefore, the drug should be used only when the benefits to the mother outweigh the potential risks to the fetus. Phenothiazines readily cross the placenta. Whether there is an increased risk of major malformations has not been clearly established. Data collected from the Swedish Medical Birth Registry showed an increased risk of malformations (e.g., atrial or ventricular septal defects) with an estimated odds ratio of 1.52. The investigators analyzed registry data from 576 infants exposed to antipsychotics in utero. Of the 35 infants exposed to thioridazine, there was one major malformation (Tetralogy of Fallot). Among the 201 women exposed to any phenothiazine during early pregnancy, there was a 3% incidence of malformations. Other findings included a nearly doubling of the risk for gestational diabetes and a 40% increased risk for cesarean delivery. Because no certain drug specificity was found for the observed outcomes, the authors concluded that underlying pathology or unidentified confounders could possibly explain the findings. Adverse effects such as extrapyramidal symptoms, agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported after delivery in neonates exposed to antipsychotics during the third trimester. These effects have varied in severity from self-limited to requiring intensive care unit stays and prolonged hospitalization. Neonates exhibiting signs or symptoms of extrapyramidal effects or withdrawal should be carefully monitored. The impact of in utero exposure to antidepressants or antipsychotics compared to no psychotropic exposure was assessed in infants 6 months of age using the Infant Neurological International Battery (INFANIB), a neuromotor exam that tests posture, tone, reflexes, and motor skills, and using a visual habituation paradigm of a neutral female face. The infants exposed to antipsychotics (n = 22) showed significantly lower INFANIB scores than those exposed to an antidepressant (n = 202) or no psychotropic drug (n = 85). There were no significant differences regarding habituation between the medication exposure groups. The knowledge about long-term neurobehavioral effects is limited for all antipsychotics and requires further investigation. According to the American Psychiatric Association treatment guidelines for schizophrenia, consider pregnancy testing in women of childbearing potential prior to initiation of an antipsychotic. 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. One 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; therefore, patient registration is encouraged. For more information, contact the registry at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry or by phone 1-866-961-2388. It is not known if antipsychotics, through their effect on prolactin, affect labor or obstetric delivery. However, if phenothiazines are given for nausea or other necessary purposes during labor and delivery, it is prudent to monitor heart rate and blood pressure to detect possible maternal or fetal hypotension or other effects. In addition, there is consistent evidence of an increased likelihood of preterm delivery associated with conventional antipsychotic use during pregnancy, with one study reporting an odds ratio of 2.46 following exposure to a conventional antipsychotic.

    Breast-feeding

    Based on recommendations for other phenothiazines, thioridazine use is not recommended in women who are breast-feeding. Phenothiazines are excreted into breast milk; drowsiness, lethargy, and developmental delays have been reported in the nursing infant. The physiology of the infant should be considered when evaluating the risk of exposure to phenothiazines. Phenothiazines may also induce elevated prolactin concentrations and galactorrhea, and thus may interfere with proper lactation. The American Academy of Pediatrics (AAP) classifies chlorpromazine, a related phenothiazine, as a drug for which the effects on a nursing infant are unknown but may be of concern due to drowsiness or lethargy in the infant, a decline in developmental scores, and drug-induced galactorrhea in the mother. Due to individual variability in response to antipsychotics, it may be prudent to continue the existing regimen if ongoing treatment is deemed necessary during breast-feeding; however, alternate medications for consideration include atypical agents such as olanzapine or quetiapine. It should be noted that data regarding the safety of atypical antipsychotics during breast-feeding are limited and chronic administration of any antipsychotic during breast-feeding should be avoided if possible. Regardless of the antipsychotic used, the nursing infant should be closely monitored for excessive drowsiness, lethargy, and developmental delays. Combination treatment with antipsychotics may increase the risk of these adverse events. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Breast cancer, hyperprolactinemia, infertility

    Phenothiazine antipsychotics, like thioridazine, stimulate the release of prolactin and may induce infertility in either men or women, or may induce other endocrine abnormalities. Some hyperprolactinemic women with normal menstruation may have an increased number of anovulatory cycles, which may result in subfertility. Some human breast cancers may be prolactin-dependent and therefore phenothiazines should be used extremely cautiously in patients who have a history of breast cancer. Neither clinical or epidemiological evidence to date have supported an association between phenothiazine use and breast cancer, although the available evidence is considered too limited to be conclusive. Close monitoring for adverse endocrine effects, such as hyperprolactinemia, is advisable during use of antipsychotics.

    Radiographic contrast administration

    Phenothiazines, like thioridazine, can lower the seizure threshold. Because of a potential increased risk of seizures, phenothiazines should not be used during intrathecal radiographic contrast administration. Phenothiazines should be discontinued 48 hours before the myelography and should not be resumed until at least 24 hours after the procedure.

    Suicidal ideation

    The possibility of a suicide attempt is inherent in patients with symptoms of depression concomitantly with other psychoses. Patients with a history of suicidal ideation and who are at high risk for suicide attempt should be closely supervised during initial drug therapy with the phenothiazines like thioridazine. The phenothiazines should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose.

    Ambient temperature increase, dehydration, hyperthermia, hypothermia, strenuous exercise

    Antipsychotics have been reported to disrupt the body's ability to reduce core body temperature presumably through effects in the hypothalamus, and they predispose patients to hyperthermia. Patients receiving thioridazine should be advised of conditions that contribute to an elevation in core body temperature (e.g., strenuous exercise, ambient temperature increase, or dehydration). A less frequently described alteration in thermoregulatory processes reported with both conventional and atypical antipsychotics is hypothermia. Thermoregulation is multi-factorial; however, the dopaminergic system appears to have a primary role, and serotonin may also have modulatory activity (5-HT2a receptors). Most cases of hypothermia associated with antipsychotics have occurred in conjunction with other potential precipitating factors such as hypothyroidism, sepsis, organic brain injury, or environmental temperature. Hypothermia appears to occur more frequently during initiation of antipsychotic therapy or after dose increases. Of note, hypothermia may increase the risk of prolonging the QT interval when using thioridazine.

    Dysphagia

    Patients with dysphagia or who are at risk for aspiration should be closely monitored while receiving thioridazine. Antipsychotics have been associated with esophageal dysmotility and aspiration of gastric contents, which may increase the incidence of aspiration pneumonia in susceptible patient populations, such as those with severe Alzheimer's disease.[54413]

    ADVERSE REACTIONS

    Severe

    cerebral edema / Early / 0-1.0
    ileus / Delayed / 0-1.0
    neuroleptic malignant syndrome / Delayed / Incidence not known
    tardive dyskinesia / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    pancytopenia / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    aplastic anemia / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    bronchospasm / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    laryngeal edema / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    visual impairment / Early / Incidence not known
    corneal opacification / Delayed / Incidence not known
    retinopathy / Delayed / Incidence not known
    asphyxia / Early / Incidence not known
    torsade de pointes / Rapid / Incidence not known
    bradycardia / Rapid / Incidence not known
    ventricular tachycardia / Early / Incidence not known
    cardiac arrest / Early / Incidence not known
    stroke / Early / Incidence not known
    water intoxication / Delayed / Incidence not known
    SIADH / Delayed / Incidence not known
    lupus-like symptoms / Delayed / Incidence not known

    Moderate

    pseudoparkinsonism / Delayed / 1.0-10.0
    dystonic reaction / Delayed / 1.0-10.0
    akathisia / Delayed / 1.0-10.0
    constipation / Delayed / 1.0-10.0
    psychosis / Early / 0-1.0
    confusion / Early / 0-1.0
    jaundice / Delayed / 0-1.0
    cholestasis / Delayed / 0-1.0
    parotitis / Delayed / 0-1.0
    orthostatic hypotension / Delayed / 10.0
    hypotension / Rapid / 10.0
    myasthenia / Delayed / Incidence not known
    peripheral edema / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known
    contact dermatitis / Delayed / Incidence not known
    erythema / Early / Incidence not known
    atopic dermatitis / Delayed / Incidence not known
    blurred vision / Early / Incidence not known
    hepatitis / Delayed / Incidence not known
    dysphagia / Delayed / Incidence not known
    QT prolongation / Rapid / Incidence not known
    hypertension / Early / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    hyperprolactinemia / Delayed / Incidence not known
    ejaculation dysfunction / Delayed / Incidence not known
    infertility / Delayed / Incidence not known
    urinary retention / Early / Incidence not known
    urinary incontinence / Early / Incidence not known
    priapism / Early / Incidence not known
    impotence (erectile dysfunction) / Delayed / Incidence not known
    galactorrhea / Delayed / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    hypoglycemia / Early / Incidence not known
    glycosuria / Early / Incidence not known
    hyperthermia / Delayed / Incidence not known
    hyponatremia / Delayed / Incidence not known

    Mild

    dizziness / Early / 1.0-10.0
    vomiting / Early / 1.0-10.0
    nausea / Early / 1.0-10.0
    headache / Early / 0-1.0
    lethargy / Early / 0-1.0
    photosensitivity / Delayed / 0-1.0
    drowsiness / Early / 10.0
    weight gain / Delayed / 10.0
    xerostomia / Early / 10.0
    appetite stimulation / Delayed / 10.0
    nasal congestion / Early / Incidence not known
    purpura / Delayed / Incidence not known
    fever / Early / Incidence not known
    hyperhidrosis / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    pruritus / Rapid / Incidence not known
    pallor / Early / Incidence not known
    skin hyperpigmentation / Delayed / Incidence not known
    seborrhea / Delayed / Incidence not known
    miosis / Early / Incidence not known
    mydriasis / Early / Incidence not known
    hypersalivation / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    diarrhea / Early / Incidence not known
    gynecomastia / Delayed / Incidence not known
    menstrual irregularity / Delayed / Incidence not known
    libido decrease / Delayed / Incidence not known
    mastalgia / Delayed / Incidence not known
    polyuria / Early / Incidence not known
    amenorrhea / Delayed / Incidence not known
    breast enlargement / Delayed / Incidence not known
    hypothermia / Delayed / Incidence not known
    polydipsia / Early / Incidence not known

    DRUG INTERACTIONS

    Abarelix: (Minor) Abarelix can cause QT prolongation. In a single, active-controlled, clinical study comparing abarelix to LHRH agonist plus nonsteroidal antiandrogen, periodic electrocardiograms were performed. Both therapies prolonged the mean QTc interval by >10 msec from baseline. In approximately 20% of 340 patients, the QTc increased more than 30 milliseconds from baseline or the end-of-treatment QTc values were more than 450 milliseconds. The effect of abarelix on the QT interval may be due to androgen deprivation or other variables, as similar effects were seen in men that received a gonadotropin-releasing hormone (GnRH) agonist with a nonsteroidal antiandrogen. Patients with a baseline QTc value greater than 450 milliseconds may not be appropriate candidates for abarelix receipt. Prescribers need to weigh the potential benefits and risks of abarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Agents with a possible risk for QT prolongation and TdP include phenothiazines.
    Abiraterone: (Contraindicated) Concomitant use of thioridazine and abiraterone is contraindicated due to the risk of QT prolongation and torsade de pointes (TdP) from elevated plasma concentrations of thioridazine. Thioridazine is a CYP2D6 substrate; abiraterone is an inhibitor of this enzyme.
    Acarbose: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
    Acetaminophen; Aspirin; Diphenhydramine: (Contraindicated) Diphenhydramine is a moderate inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, occurring from elevated serum concentrations of thioridazine. Also, additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as diphenhydramine. Consider if an alternative to diphenhydramine would be appropriate for the patient's condition.
    Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking thioridazine. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Acetaminophen; Caffeine; Pyrilamine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as pyrilamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Acetaminophen; Chlorpheniramine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Acetaminophen; Codeine: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking thioridazine. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as doxylamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as dichloralphenazone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Acetaminophen; Diphenhydramine: (Contraindicated) Diphenhydramine is a moderate inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, occurring from elevated serum concentrations of thioridazine. Also, additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as diphenhydramine. Consider if an alternative to diphenhydramine would be appropriate for the patient's condition.
    Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Acetaminophen; Hydrocodone: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking thioridazine. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Acetaminophen; Oxycodone: (Major) Concomitant use of oxycodone with phenothiazines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with phenothiazines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Monitor for signs of hypotension after starting or titrating the dosage of oxycodone. There is an increased risk of severe hypotension in patients whose ability to maintain blood pressure has already been compromised by concurrent administration of phenothiazines.
    Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as pyrilamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Acetaminophen; Pentazocine: (Moderate) Concomitant use of pentazocine with other CNS depressants, such as phenothiazines, can potentiate respiratory depression, CNS depression, and sedation. Pentazocine should be used cautiously with phenothiazines.
    Acetohexamide: (Moderate) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. Also, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure.
    Alfentanil: (Moderate) Concomitant use of alfentanil with other CNS depressants, including the phenothiazines, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Alfuzosin: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Because of the potential for TdP, use of alfuzosin with thioridazine is contraindicated.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Alogliptin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
    Alogliptin; Metformin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
    Alogliptin; Pioglitazone: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
    Alosetron: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like phenothiazines, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
    Alpha-glucosidase Inhibitors: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
    Alprazolam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
    Amantadine: (Moderate) Although the mechanism of amantadine is not clear, it may potentiate the actions of dopamine. Since phenothiazines are dopamine antagonists, these drugs are best avoided when possible in patients with Parkinson's disease who require amantadine therapy. Also, the anticholinergic effects of phenothiazines can be additive to those of amantadine.
    Amifampridine: (Major) Carefully consider the need for concomitant treatment with phenothiazines and amifampridine, as coadministration may increase the risk of seizures. Consider an alternative to the phenothiazine. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Phenothiazines may lower seizure threshold and should be used with caution with concomitant medications which may also affect seizure threshold.
    Amikacin: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask vestibular symptoms that are associated with ototoxicity induced by various medications, including the aminoglycosides.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Aminoglycosides: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask vestibular symptoms that are associated with ototoxicity induced by various medications, including the aminoglycosides.
    Aminolevulinic Acid: (Moderate) Phenothiazines may increase the photosensitizing effects of photosensitizing agents used in photodynamic therapy. Patients should limit ultra-violet exposure.
    Amiodarone: (Contraindicated) Avoid concomitant use of thioridazine and amiodarone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation.
    Amisulpride: (Contraindicated) Coadministration of thioridazine with amisulpride is contraindicated due to the risk of additive QT prolongation and torsade de pointes (TdP). Thioridazine is associated with a well-established risk of QT prolongation and TdP. Amisulpride causes dose- and concentration- dependent QT prolongation.
    Amitriptyline: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension, including tricyclic antidepressants (TCAs). In addition to additive effects on the cardiovascular system, additive anticholinergic effects and sedation may be observed.
    Amlodipine; Celecoxib: (Contraindicated) Coadministration of celecoxib and thioridazine is contraindicated due to the potential for celecoxib to enhance the exposure and toxicity of thioridazine. Elevated thioridazine concentrations would be expected to augment the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious cardiac arrhythmias, such as torsade de pointes. Celecoxib is a CYP2D6 inhibitor, and thioridazine is a CYP2D6 substrate.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Amobarbital: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Amoxapine: (Moderate) Use caution during coadministration of amoxapine and thioridazine. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of the seizure threshold are potential problems with the combined use of amoxapine and many antipsychotics, such as phenothiazines.
    Amoxicillin; Clarithromycin; Omeprazole: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with clarithromycin which, when combined with a thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Anagrelide: (Contraindicated) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. Thioridazine, a phenothiazine, is associated with an established risk of QT prolongation andTdP and is contraindicated for use with other drugs that are known to prolong the QT interval.
    Anticholinergics: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties like thioridazine are used concomitantly with anticholinergic agents. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the interacting agent.
    Anxiolytics; Sedatives; and Hypnotics: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered with other CNS depressant drugs and they should be used cautiously with anxiolytic, sedative, and hypnotics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of hypnotics and other CNS depressants than with use of a hypnotic alone.
    Apomorphine: (Contraindicated) Thioridazine is considered contraindicated for use along with apomorphine which, when combined with thioridazine, may prolong the QT interval and increase the risk of torsade de pointes (TdP), and/or cause orthostatic hypotension. Thioridazine is associated with a well-established risk of QT prolongation and TdP. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. In addition, thioridazine and apomorphine may reduce the effects of each other through opposing effects on dopamine.
    Apraclonidine: (Minor) No specific drug interactions were identified with systemic agents and apraclonidine during clinical trials. Theoretically, apraclonidine might potentiate the effects of CNS depressant drugs such as phenothiazines.
    Aripiprazole: (Contraindicated) Thioridazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP) and is contraindicated for use with other drugs that are known to prolong the QT interval. Other antipsychotics that may cause QT prolongation and TdP include aripiprazole. Also, coadministration of thioridazine with atypical antipsychotics may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Arsenic Trioxide: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Because of the potential for TdP, use of arsenic trioxide with thioridazine is contraindicated.
    Artemether; Lumefantrine: (Contraindicated) The concomitant use of artemether; lumefantrine and thioridazine is contraindicated. Artemether; lumefantrine is an inhibitor and thioridazine is a substrate/inhibitor of the CYP2D6 isoenzyme; therefore, coadministration may lead to increased thioridazine concentrations. Furthermore, thioridazine is contraindicated with CYP2D6 inhibitors due to the potential for QT prolongation. 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.
    Articaine; Epinephrine: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
    Asenapine: (Contraindicated) Thioridazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP) and is contraindicated for use with other drugs that are known to prolong the QT interval, such as asenapine.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking thioridazine. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Additive anticholinergic effects may be seen when thioridazine is used concomitantly with other drugs having antimuscarinic activity such as orphenadrine. Additive sedation may also occur.
    Aspirin, ASA; Carisoprodol: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential for additive hypotension and excessive CNS effects (sedation and dizziness), which can impair the ability to undertake tasks requiring mental alertness.
    Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking thioridazine. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential for additive hypotension and excessive CNS effects (sedation and dizziness), which can impair the ability to undertake tasks requiring mental alertness.
    Aspirin, ASA; Oxycodone: (Major) Concomitant use of oxycodone with phenothiazines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with phenothiazines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Monitor for signs of hypotension after starting or titrating the dosage of oxycodone. There is an increased risk of severe hypotension in patients whose ability to maintain blood pressure has already been compromised by concurrent administration of phenothiazines.
    Atazanavir; Cobicistat: (Contraindicated) Cobicistat is a mild inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, occurring from elevated serum concentrations of thioridazine.
    Atenolol; Chlorthalidone: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Atomoxetine: (Contraindicated) Avoid concomitant use of thioridazine and atomoxetine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Atropine; Difenoxin: (Moderate) Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth muscle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. The effects can be additive to other agents with CNS and anticholinergic effects, such as the phenothiazines. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Azelastine: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including phenothiazines.
    Azelastine; Fluticasone: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including phenothiazines.
    Azilsartan; Chlorthalidone: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Azithromycin: (Contraindicated) Avoid concomitant use of thioridazine and azithromycin due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Baclofen: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
    Barbiturates: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Bedaquiline: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Thioridazine is considered contraindicated for use along with bedaquiline which, when combined with thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Belladonna; Opium: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Bendroflumethiazide; Nadolol: (Moderate) Concomitant treatment with nadolol and phenothiazines, especially in large doses, can have an additive hypotensive effect. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with thioridazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If benzhydrocodone is initiated in a patient taking thioridazine, reduce initial dosage and titrate to clinical response. If thioridazine is initiated a patient taking an opioid agonist, use a lower initial dose of thioridazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Thioridazine is contraindicated in patients with drug-induced CNS depression.
    Benzodiazepines: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
    Berotralstat: (Contraindicated) Coadministration of thioridazine and berotralstat is contraindicated due to the potential for increased thioridazine exposure. Increased plasma concentrations of thioridazine are expected to increase the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as torsade de pointes type arrhythmias. Thioridazine is a CYP2D6 substrate and berotralstat is a CYP2D6 inhibitor.
    Bethanechol: (Moderate) Drugs that possess antimuscarinic properties, such as thioridazine, are pharmacologic opposites of bethanechol. These agents should not be used with bethanechol except when the specific intent is to counteract excessive actions of one or the other.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Contraindicated) Avoid concomitant use of metronidazole and thioridazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Bismuth Subsalicylate: (Moderate) Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. The concomitant administration of phenothiazines may produce additive effects.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Contraindicated) Avoid concomitant use of metronidazole and thioridazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. (Moderate) Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. The concomitant administration of phenothiazines may produce additive effects.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Brexpiprazole: (Major) Caution is advisable during concurrent use of brexpiprazole with other antipsychotics such as thioridazine. Brexpiprazole is partially metabolized by CYP2D6 and thioridazine is a moderate inhibitor of CYP2D6. The manufacturer of brexpiprazole recommends that the brexpiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving a moderate to strong inhibitor of CYP3A4 in combination with a moderate to strong inhibitor of CYP2D6. Therefore, if thioridazine is used in combination with brexpiprazole and a moderate to strong CYP3A4 inhibitor, the brexpiprazole dose should be adjusted and the patient should be carefully monitored for brexpiprazole-related adverse reactions. The risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, or seizures may be increased during combined use of brexpiprazole and thioridazine; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is deemed necessary. Thioridazine has a high potential to cause sedation, orthostasis, and anticholinergic effects, and a low potential of causing extrapyramidal effects. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Bromocriptine: (Major) Avoid concurrent use of phenothiazines and bromocriptine when possible. Bromocriptine may interact with dopamine antagonists such as the phenothiazines. The phenothiazines are noted to result in a decreased efficacy of bromocriptine. The prolactin-lowering effect of bromocriptine is antagonized; the elevation in prolactin levels produced by phenothiazines persists with chronic administration. In addition, bromocriptine, a dopamine agonist, may theoretically diminish the effectiveness of central dopamine antagonists such as the phenothiazines; however, such interactions are not certain.
    Brompheniramine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as brompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as brompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including phenothiazines. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as brompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as brompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Brompheniramine; Phenylephrine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as brompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Brompheniramine; Pseudoephedrine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as brompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as brompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Bupivacaine; Epinephrine: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
    Buprenorphine: (Contraindicated) Avoid concomitant use of thioridazine and buprenorphine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Buprenorphine; Naloxone: (Contraindicated) Avoid concomitant use of thioridazine and buprenorphine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Bupropion: (Contraindicated) Bupropion is a strong inhibitor of CYP2D6 and the use of thioridazine with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias resulting from elevated serum concentrations of thioridazine. In addition, bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines, such as thioridazine, on lowering the seizure threshold.
    Bupropion; Naltrexone: (Contraindicated) Bupropion is a strong inhibitor of CYP2D6 and the use of thioridazine with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias resulting from elevated serum concentrations of thioridazine. In addition, bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines, such as thioridazine, on lowering the seizure threshold. (Moderate) Patients receiving phenothiazines and naltrexone concomitantly have had symptoms of somnolence and lethargy.
    Butabarbital: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Butalbital; Acetaminophen: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Butalbital; Acetaminophen; Caffeine: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking thioridazine. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Butorphanol: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as phenothiazines, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
    Cabergoline: (Moderate) Cabergoline should generally not be coadministered with phenothiazines due to mutually antagonistic effects on dopaminergic function. The dopamine antagonist action of phenothiazines may diminish the prolactin-lowering ability of cabergoline while the dopamine agonist effects of cabergoline may exacerbate a psychotic disorder, reducing the effectiveness of antipsychotics such as phenothiazines.
    Cabotegravir; Rilpivirine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and TdP. Thioridazine is considered contraindicated for use along with rilpivirine which, when combined with thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Calcium, Magnesium, Potassium, Sodium Oxybates: (Major) Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with phenothiazines.
    Canagliflozin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted.
    Canagliflozin; Metformin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
    Canakinumab: (Moderate) Monitor for an altered patient response to thioridazine if coadministration with canakinumab is necessary. Canakinumab therapy may restore CYP450 activities to higher levels compared to pretreatment, thus leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index may have fluctuations in drug levels and therapeutic effect. This effect on CYP450 enzyme activity may persist for several weeks after stopping canakinumab. Thioridazine is a CYP2D6 substrate and narrow therapeutic index drug.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and phenothiazines. CNS depressants can potentiate the effects of cannabidiol.
    Capsaicin; Metaxalone: (Moderate) Phenothiazines can potentiate the CNS-depressant action of skeletal muscle relaxants like metaxalone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Carbetapentane; Chlorpheniramine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including phenothiazines.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including phenothiazines. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Contraindicated) Diphenhydramine is a moderate inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, occurring from elevated serum concentrations of thioridazine. Also, additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as diphenhydramine. Consider if an alternative to diphenhydramine would be appropriate for the patient's condition. (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including phenothiazines. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Carbetapentane; Guaifenesin: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including phenothiazines.
    Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including phenothiazines. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including phenothiazines. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as pyrilamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including phenothiazines. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Carbetapentane; Pseudoephedrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including phenothiazines.
    Carbetapentane; Pyrilamine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as pyrilamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including phenothiazines.
    Carbidopa; Levodopa: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
    Carbidopa; Levodopa; Entacapone: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
    Carbinoxamine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as carbinoxamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as carbinoxamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Carbinoxamine; Phenylephrine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as carbinoxamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Carbinoxamine; Pseudoephedrine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as carbinoxamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Cariprazine: (Major) Avoid use of these drugs together due to duplicative therapeutic effects and additive risks for drowsiness, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. Cariprazine, like other antipsychotics, has the potential to impair judgment, thinking, or motor skills. The use of cariprazine with other antipsychotic agents, such as the phenothiazines, would be expected to have additive risks for pharmacologic effects and adverse reactions. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during combined use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Carisoprodol: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential for additive hypotension and excessive CNS effects (sedation and dizziness), which can impair the ability to undertake tasks requiring mental alertness.
    Carteolol: (Moderate) Concomitant treatment with carteolol and phenothiazines, especially in large doses, can have an additive hypotensive effect.
    Carvedilol: (Minor) Inhibitors of the hepatic CYP450 isozyme CYP 2D6, such as thioridazine, may inhibit the hepatic oxidative metabolism of carvedilol.
    Celecoxib: (Contraindicated) Coadministration of celecoxib and thioridazine is contraindicated due to the potential for celecoxib to enhance the exposure and toxicity of thioridazine. Elevated thioridazine concentrations would be expected to augment the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious cardiac arrhythmias, such as torsade de pointes. Celecoxib is a CYP2D6 inhibitor, and thioridazine is a CYP2D6 substrate.
    Celecoxib; Tramadol: (Contraindicated) Coadministration of celecoxib and thioridazine is contraindicated due to the potential for celecoxib to enhance the exposure and toxicity of thioridazine. Elevated thioridazine concentrations would be expected to augment the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious cardiac arrhythmias, such as torsade de pointes. Celecoxib is a CYP2D6 inhibitor, and thioridazine is a CYP2D6 substrate. (Major) Concurrent use of tramadol and thioridazine should be avoided if possible. Antipsychotics may enhance the seizure risk of tramadol. In addition, thioridazine has clinically significant CYP2D6 inhibitory effects and has the potential to decrease the metabolism of CYP2D6 substrates such as tramadol. Although the full pharmacologic impact of increased tramadol exposure is unknown, close monitoring for serious adverse effects, such as seizures, is advisable. In addition, serotonin syndrome may occur during use of tramadol with medications that impair its metabolism. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, hyperreflexia, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Because the analgesic activity of tramadol is due to the activity of both the parent drug and the O-desmethyltramadol metabolite (M1), CYP2D6 inhibition by thioridazine may alter the analgesic response to tramadol. Additive CNS depression may also be seen with the concomitant use of tramadol and thioridazine.
    Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and a phenothiazine. Concurrent use may result in additive CNS depression.
    Central-acting adrenergic agents: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
    Ceritinib: (Contraindicated) Thioridazine is contraindicated for use along with agents such as ceritinib that may prolong the QT interval and increase the risk of torsades de pointes (TdP), and/or cause orthostatic hypotension when combined with a phenothiazine. Thioridazine is associated with a well-established risk of QT prolongation and TdP, and ceritinib is associated with concentration-dependent QT prolongation.
    Cetrorelix: (Moderate) Drugs that cause hyperprolactinemia, such as antipsychotics, should not be administered concomitantly with cetrorelix since hyperprolactinemia downregulates the number of pituitary GnRH receptors.
    Charcoal: (Major) Phenothiazine absorption is reduced when coadministered with activated charcoal. Concomitant administration of phenothiazines and activated charcoal dietary supplements is not recommended. Activated charcoal may be appropriate in phenothiazine overdose situations, as charcoal absorbs the phenothiazines and also enhances drug elimination.
    Chlophedianol; Dexbrompheniramine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as dexbrompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as dexchlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Chlordiazepoxide: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
    Chlordiazepoxide; Amitriptyline: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension, including tricyclic antidepressants (TCAs). In addition to additive effects on the cardiovascular system, additive anticholinergic effects and sedation may be observed. (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
    Chlordiazepoxide; Clidinium: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
    Chloroquine: (Contraindicated) Coadministration of chloroquine with thioridazine is contraindicated due to the increased risk of QT prolongation. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Thioridazine is associated with a well-established risk of QT prolongation and TdP.
    Chlorothiazide: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Chlorpheniramine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Chlorpheniramine; Codeine: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking thioridazine. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Chlorpheniramine; Dextromethorphan: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking thioridazine. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Chlorpheniramine; Hydrocodone: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking thioridazine. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Chlorpheniramine; Phenylephrine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Chlorpheniramine; Pseudoephedrine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Chlorpromazine: (Contraindicated) Thioridazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP) and is contraindicated for use with other drugs that are known to prolong the QT interval, such as chlorpromazine. In addition, coadministration may increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, or seizures.
    Chlorpropamide: (Moderate) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. Also, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure.
    Chlorthalidone: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Chlorthalidone; Clonidine: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Chlorzoxazone: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Cimetidine: (Contraindicated) Cimetidine is a moderate inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, due to elevated serum concentrations of thioridazine. Consider an alternative to cimetidine for patients taking thioridazine.
    Cinacalcet: (Contraindicated) Coadministration of cinacalcet, a strong CYP2D6 inhibitor, and thioridazine, a CYP2D6 substrate, is contraindicated, as concurrent use may result in increased exposure to thioridazine. Elevated thioridazine concentrations would be expected to augment the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as torsade de pointes.
    Ciprofloxacin: (Contraindicated) Avoid concomitant use of thioridazine and ciprofloxacin due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Cisapride: (Contraindicated) Coadministration of cisapride and thioridazine is contraindicated due to the risk for serious adverse events, such as torsade de pointes (TdP). QT prolongation and ventricular arrhythmias, including TdP and death, have been reported with cisapride. Thioridazine is also associated with a well-established risk of QT prolongation and TdP.
    Citalopram: (Contraindicated) 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.
    Clarithromycin: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with clarithromycin which, when combined with a thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Clemastine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as clemastine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Clindamycin; Tretinoin: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Clobazam: (Contraindicated) Clobazam is a mild inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, occurring from elevated serum concentrations of thioridazine.
    Clofazimine: (Contraindicated) Avoid concomitant use of clofazimine and thioridazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Clomipramine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension, including tricyclic antidepressants (TCAs). In addition to additive effects on the cardiovascular system, additive anticholinergic effects and sedation may be observed.
    Clonazepam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
    Clorazepate: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
    Clozapine: (Contraindicated) Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Because thioridazine has an established risk of QT prolongation and TdP, concurrent use with clozapine is considered contraindicated. In addition, coadministration may increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. Clozapine is metabolized by CYP1A2, CYP3A4, and CYP2D6. Antipsychotic drugs known to inhibit the activity of CYP2D6 include thioridazine. Elevated plasma concentrations of clozapine occurring through inhibition of CYP1A2, CYP3A4, or CYP2D6 may potentially increase the risk of life-threatening arrhythmias or other adverse effects.
    Cobicistat: (Contraindicated) Cobicistat is a mild inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, occurring from elevated serum concentrations of thioridazine.
    Codeine: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking thioridazine. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Codeine; Guaifenesin: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking thioridazine. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking thioridazine. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Codeine; Phenylephrine; Promethazine: (Contraindicated) Due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of promethazine and thioridazine is considered contraindicated. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes. (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking thioridazine. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Codeine; Promethazine: (Contraindicated) Due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of promethazine and thioridazine is considered contraindicated. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes. (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking thioridazine. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    COMT inhibitors: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and COMT inhibitors may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
    Crizotinib: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of crizotinib with thioridazine is contraindicated. Thioridazine is associated with a well-established risk of QT prolongation and TdP. Crizotinib has also been associated with concentration-dependent QT prolongation.
    Cyclobenzaprine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like thioridazine and cyclobenzaprine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    Dacomitinib: (Contraindicated) Coadministration of dacomitinib and thioridazine is contraindicated, as concurrent use may result in increased exposure to thioridazine. Elevated thioridazine concentrations would be expected to augment the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as torsade de pointes. Thioridazine is a CYP2D6 substrate; dacomitinib is a strong CYP2D6 inhibitor.
    Dantrolene: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Dapagliflozin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted.
    Dapagliflozin; Metformin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
    Dapagliflozin; Saxagliptin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
    Darifenacin: (Contraindicated) Coadministration of thioridazine and darifenacin is contraindicated due to the potential for increased thioridazine exposure. Increased plasma concentrations of thioridazine are expected to increase the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as torsade de pointes type arrhythmias. Thioridazine is a CYP2D6 substrate; darifenacin is a moderate CYP2D6 inhibitor.
    Darunavir: (Major) Decreased thioridazine doses may be required when coadministered with darunavir/ritonavir. Darunavir/ritonavir is expected to decrease the hepatic metabolism of the thioridazine, resulting in increased thioridizine concentrations. If coadministration of these drugs is warranted, do so with caution and careful monitoring.
    Darunavir; Cobicistat: (Contraindicated) Cobicistat is a mild inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, occurring from elevated serum concentrations of thioridazine. (Major) Decreased thioridazine doses may be required when coadministered with darunavir/ritonavir. Darunavir/ritonavir is expected to decrease the hepatic metabolism of the thioridazine, resulting in increased thioridizine concentrations. If coadministration of these drugs is warranted, do so with caution and careful monitoring.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Contraindicated) Cobicistat is a mild inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, occurring from elevated serum concentrations of thioridazine. (Major) Decreased thioridazine doses may be required when coadministered with darunavir/ritonavir. Darunavir/ritonavir is expected to decrease the hepatic metabolism of the thioridazine, resulting in increased thioridizine concentrations. If coadministration of these drugs is warranted, do so with caution and careful monitoring.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Close clinical monitoring is recommended during coadministration; thioridazine dose reductions may be required. The plasma concentrations of thioridazine may be elevated when administered concurrently with ritonavir. Elevated levels of thioridazine may result in prolongation of the QTc interval and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as torsades de pointes.
    Dasatinib: (Contraindicated) Coadministration of dasatinib and thioridazine is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Thioridazine is associated with a well-established risk of QT prolongation and TdP. Thioridazine is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Degarelix: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of degarelix with thioridazine is contraindicated; the efficacy of degarelix may also be reduced. Thioridazine is associated with a well-established risk of QT prolongation and TdP. Thioridazine is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Androgen deprivation therapy (i.e., degarelix) may also prolong the QT/QTc interval. Additionally, thioridazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; degarelix is a GnRH analog.
    Delavirdine: (Contraindicated) Delavirdine is a moderate inhibitor of CYP2D6 in vitro and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, due to elevated serum concentrations of thioridazine.
    Desflurane: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension, such as halogenated anesthetics.
    Desipramine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension, including tricyclic antidepressants (TCAs). In addition to additive effects on the cardiovascular system, additive anticholinergic effects and sedation may be observed.
    Desogestrel; Ethinyl Estradiol: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Desvenlafaxine: (Major) Desvenlafaxine is a mild inhibitor of CYP2D6 at a dose of 400 mg/day and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, occurring from elevated serum concentrations of thioridazine.
    Deutetrabenazine: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of deutetrabenazine with thioridazine is contraindicated. Thioridazine is associated with a well-established risk of QT prolongation and TdP. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Also, deutetrabenazine is a reversible, dopamine depleting drug and thioridazine is a dopamine antagonist. The risk for parkinsonism, neuroleptic malignant syndrome (NMS), and akathisia may be increased with concomitant administration. Concurrent use of deutetrabenazine and drugs that cause CNS depression, such as thioridazine, may have additive effects and worsen drowsiness or sedation.
    Dexbrompheniramine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as dexbrompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Dexbrompheniramine; Pseudoephedrine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as dexbrompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Dexchlorpheniramine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as dexchlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as dexchlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Dexmedetomidine: (Moderate) Coadministration of dexmedetomidine with phenothiazines to lead to an enhancement of anesthetic, sedative, or cardiovascular effects. Dosage reduction of either agent may be required.
    Dextromethorphan; Bupropion: (Contraindicated) Bupropion is a strong inhibitor of CYP2D6 and the use of thioridazine with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias resulting from elevated serum concentrations of thioridazine. In addition, bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines, such as thioridazine, on lowering the seizure threshold.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Contraindicated) Diphenhydramine is a moderate inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, occurring from elevated serum concentrations of thioridazine. Also, additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as diphenhydramine. Consider if an alternative to diphenhydramine would be appropriate for the patient's condition. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Dextromethorphan; Quinidine: (Contraindicated) Because of the potential for torsade de pointes (TdP), concurrent use of quinidine and thioridazine is contraindicated. Class IA antiarrhythmics and thioridazine are associated with a well-established risk of QT prolongation and TdP. Thioridazine is considered contraindicated for use with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Diazepam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
    Diethylpropion: (Minor) Use of diethylpropion with phenothiazines may antagonize the anorectic effects of diethylpropion.
    Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
    Dimenhydrinate: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as dimenhydrinate. Patients should be informed to read non-prescription motion sickness, allergy, sleep, and cough and cold product labels carefully for additional interacting antihistamines.
    Dipeptidyl Peptidase-4 Inhibitors: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
    Diphenhydramine: (Contraindicated) Diphenhydramine is a moderate inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, occurring from elevated serum concentrations of thioridazine. Also, additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as diphenhydramine. Consider if an alternative to diphenhydramine would be appropriate for the patient's condition.
    Diphenhydramine; Ibuprofen: (Contraindicated) Diphenhydramine is a moderate inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, occurring from elevated serum concentrations of thioridazine. Also, additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as diphenhydramine. Consider if an alternative to diphenhydramine would be appropriate for the patient's condition.
    Diphenhydramine; Naproxen: (Contraindicated) Diphenhydramine is a moderate inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, occurring from elevated serum concentrations of thioridazine. Also, additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as diphenhydramine. Consider if an alternative to diphenhydramine would be appropriate for the patient's condition.
    Diphenhydramine; Phenylephrine: (Contraindicated) Diphenhydramine is a moderate inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, occurring from elevated serum concentrations of thioridazine. Also, additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as diphenhydramine. Consider if an alternative to diphenhydramine would be appropriate for the patient's condition. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Diphenoxylate; Atropine: (Moderate) Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth muscle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. The effects can be additive to other agents with CNS and anticholinergic effects, such as the phenothiazines. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Disopyramide: (Contraindicated) Because of the potential for torsade de pointes (TdP), concurrent use of disopyramide and thioridazine is contraindicated. Class IA antiarrhythmics and thioridazine are associated with a well-established risk of QT prolongation and TdP. Thioridazine is considered contraindicated for use with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. In addition, both thioridazine and disopyramide have significant anticholinergic effects that may be additive during coadministration.
    Dofetilide: (Contraindicated) Coadministration of thioridazine with dofetilide is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Both drugs are associated with a well-established risk of QT prolongation and TdP.
    Dolasetron: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of thioridazine with dolasetron is contraindicated. Thioridazine is associated with a well-established risk of QT prolongation and TdP and is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Dolasetron has also been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
    Dolutegravir; Rilpivirine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and TdP. Thioridazine is considered contraindicated for use along with rilpivirine which, when combined with thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Donepezil: (Contraindicated) Because of the potential for QT prolongation and torsade de pointes (TdP), concurrent use of thioridazine and donepezil is contraindicated. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Both donepezil and thioridazine are considered drugs with a known risk of TdP.
    Donepezil; Memantine: (Contraindicated) Because of the potential for QT prolongation and torsade de pointes (TdP), concurrent use of thioridazine and donepezil is contraindicated. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Both donepezil and thioridazine are considered drugs with a known risk of TdP.
    Dopamine: (Moderate) The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of phenothiazines.
    Doxepin: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension, including tricyclic antidepressants (TCAs). In addition to additive effects on the cardiovascular system, additive anticholinergic effects and sedation may be observed.
    Doxercalciferol: (Moderate) Cytochrome P450 enzyme inhibitors, such as thioridazine, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Doxorubicin Liposomal: (Major) Avoid coadministration of thioridazine with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Thioridazine is a CYP2D6 inhibitor and doxorubicin is a major substrate of CYP2D6. Concurrent use of CYP2D6 inhibitors with doxorubicin has resulted in clinically significant interactions.
    Doxorubicin: (Major) Avoid coadministration of thioridazine with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Thioridazine is a CYP2D6 inhibitor and doxorubicin is a major substrate of CYP2D6. Concurrent use of CYP2D6 inhibitors with doxorubicin has resulted in clinically significant interactions.
    Doxylamine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as doxylamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Doxylamine; Pyridoxine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as doxylamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Dronabinol: (Moderate) Use caution if coadministration of phenothiazines with dronabinol is necessary. Administration of dronabinol with phenothiazines (e.g., prochlorperazine) has resulted in improved antiemetic efficacy as compared to either drug alone, without additional toxicity. However, it is also possible that coadministration may result in additive dizziness, confusion, somnolence, and other CNS effects.
    Dronedarone: (Contraindicated) Concomitant use of dronedarone and thioridazine is contraindicated. Dronedarone is an inhibitor of CYP2D6. Thioridazine is a substrate for CYP2D6. Coadministration of dronedarone and thioridazine may result in increased plasma concentrations of thioridazine. In addition, thioridazine has been established to have a causal association with QT prolongation and Torsade de Pointes (TdP). 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: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Because of the potential for TdP, use of the following drugs with thioridazine is contraindicated droperidol.
    Drospirenone; Ethinyl Estradiol: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Duloxetine: (Contraindicated) Duloxetine is a moderate inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, occurring from elevated serum concentrations of thioridazine.
    Dutasteride; Tamsulosin: (Moderate) Use caution when administering tamsulosin with a CYP2D6 inhibitor such as thioridazine. 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.
    Efavirenz: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Efavirenz has also been associated with QT prolongation. Because of the potential for QT prolongation and TdP, use of efavirenz with thioridazine is contraindicated.
    Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Efavirenz has also been associated with QT prolongation. Because of the potential for QT prolongation and TdP, use of efavirenz with thioridazine is contraindicated.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Efavirenz has also been associated with QT prolongation. Because of the potential for QT prolongation and TdP, use of efavirenz with thioridazine is contraindicated.
    Eliglustat: (Contraindicated) Coadministration of thioridazine and eliglustat is contraindicated. Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP) and is contraindicated for use with other drugs that may prolong the QT interval, such as eliglustat. In addition, coadministration of thioridazine, a CYP2D6 substrate, and eliglustat, a CYP2D6 inhibitor, may result in elevated phenothiazine concentrations, further increasing the risk for serious adverse events (e.g., cardiac arrhythmias).
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) Cobicistat is a mild inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, occurring from elevated serum concentrations of thioridazine.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Cobicistat is a mild inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, occurring from elevated serum concentrations of thioridazine.
    Emapalumab: (Moderate) Monitor for decreased efficacy of thioridazine and adjust the dose as needed during coadministration with emapalumab. Thioridazine is a CYP2D6 substrate with a narrow therapeutic range. Emapalumab may normalize CYP450 activity, which may decrease the efficacy of drugs that are CYP450 substrates due to increased metabolism.
    Empagliflozin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted.
    Empagliflozin; Linagliptin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
    Empagliflozin; Linagliptin; Metformin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
    Empagliflozin; Metformin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and TdP. Thioridazine is considered contraindicated for use along with rilpivirine which, when combined with thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and TdP. Thioridazine is considered contraindicated for use along with rilpivirine which, when combined with thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Encainide: (Contraindicated) Encainide is significantly metabolized by CYP2D6 isoenzymes. Caution is recommended when administering encainide with CYP2D6 inhibitors, such as thioridazine, since encainide exhibits a narrow therapeutic range and large increases in serum concentrations may be associated with severe adverse reactions.
    Encorafenib: (Contraindicated) Coadministration of encorafenib with thioridazine is contraindicated due to the potential for QT prolongation. Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
    Entrectinib: (Contraindicated) Coadministration of thioridazine with entrectinib is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Thioridazine is associated with a well-established risk of QT prolongation and TdP. Entrectinib has been associated with QT prolongation.
    Ephedrine: (Major) Avoid use of ephedrine in patients receiving phenothiazines due to the risk of paradoxical vasodilation. Phenothiazines possess potent alpha-blocking properties, making the use of vasopressors with mixed alpha- and beta-agonist properties inappropriate. If a vasopressor is required, norepinephrine and phenylephrine are most appropriate.
    Ephedrine; Guaifenesin: (Major) Avoid use of ephedrine in patients receiving phenothiazines due to the risk of paradoxical vasodilation. Phenothiazines possess potent alpha-blocking properties, making the use of vasopressors with mixed alpha- and beta-agonist properties inappropriate. If a vasopressor is required, norepinephrine and phenylephrine are most appropriate.
    Epinephrine: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Eribulin: (Contraindicated) Eribulin has been associated with QT prolongation. Thioridazine has been specifically established to have a causal association with QT prolongation and torsade de pointes and is contraindicated for use with eribulin.
    Ertugliflozin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted.
    Ertugliflozin; Metformin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
    Ertugliflozin; Sitagliptin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
    Erythromycin: (Contraindicated) Avoid concomitant use of thioridazine and erythromycin due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Escitalopram: (Contraindicated) Because of the potential for QT prolongation and torsade de pointes (TdP), concurrent use of phenothiazine antipsychotics such as thioridazine with escitalopram is contraindicated. In addition, thioridazine is a CYP2D6 substrate, and use with a modest CYP2D6 inhibitor, such as escitalopram, can result in increased plasma concentrations, further increasing the risk for cardiac or other phenothiazine-related side effects.
    Esketamine: (Major) Closely monitor patients receiving esketamine and thioridazine for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
    Estazolam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
    Eszopiclone: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered with other CNS depressant drugs and they should be used cautiously with anxiolytic, sedative, and hypnotics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of hypnotics and other CNS depressants than with use of a hypnotic alone.
    Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
    Ethinyl Estradiol: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Ethinyl Estradiol; Norelgestromin: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Ethinyl Estradiol; Norethindrone Acetate: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Ethinyl Estradiol; Norgestrel: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Ethiodized Oil: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Phenothiazines should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Ethosuximide: (Moderate) Concomitant use of ethosuximide with phenothiazines can lower the seizure threshold and reduce the effectiveness of ethosuximide as an anticonvulsant. Additive CNS effects, such as drowsiness, may also occur.
    Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Etomidate: (Moderate) Etomidate potentiates the effects of CNS depressants including thioridazine. Additive CNS effects (e.g., oversedation, respiratory depression, and hypotension) may occur if etomidate and thioridazine are used concomitantly.
    Etonogestrel; Ethinyl Estradiol: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Everolimus: (Contraindicated) Everolimus is a mild inhibitor of CYP2D6 in vitro and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, occurring from elevated serum concentrations of thioridazine.
    Fedratinib: (Contraindicated) Concomitant use of thioridazine and fedratinib is contraindicated due to the risk of QT prolongation and torsade de pointes (TdP) from elevated plasma concentrations of thioridazine. Thioridazine is a CYP2D6 substrate; fedratinib is an inhibitor of this enzyme.
    Felbamate: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added.
    Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and thioridazine. Concurrent use may result in additive CNS depression.
    Fentanyl: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Fingolimod: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP).[ Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Because of the potential for TdP, use of fingolimod with thioridazine is contraindicated.
    Flecainide: (Contraindicated) Avoid concomitant use of thioridazine and flecainide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Flibanserin: (Moderate) The concomitant use of flibanserin with CNS depressants, such as phenothiazines, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
    Fluconazole: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Thioridazine is considered contraindicated for use along with fluconazole which, when combined with thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Flucytosine: (Minor) Because of flucytosine's ability to cause significant hematologic toxicity, it should be used cautiously with all bone marrow depressants. These include: carbamazepine, clozapine, phenothiazines, zidovudine, ZDV and other blood dyscrasia-causing medications.
    Fluocinolone; Hydroquinone; Tretinoin: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Fluoxetine: (Contraindicated) Fluoxetine is contraindicated for use with some phenothiazine antipsychotics including thioridazine. Thioridazine has an established risk of QT prolongation and torsade de pointes (TdP), and post-marketing reports suggest a possible risk of QT prolongation and TdP with fluoxetine. In addition, the metabolism of thioridazine may be decreased during use of CYP2D6 inhibitors such as fluoxetine. Due to the long half-life of fluoxetine and its active metabolite, thioridazine should not be initiated within 5 weeks after discontinuing fluoxetine. Decreased metabolism of this CYP2D6 substrates by fluoxetine may also lead to arrhythmias or other clinically important adverse reactions such as extrapyramidal symptoms.
    Fluphenazine: (Contraindicated) Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation and/or torsade de pointes (TdP). Due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of fluphenazine and thioridazine is considered contraindicated.
    Flurazepam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
    Fluvoxamine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Thioridazine is considered contraindicated for use with agents that may prolong the QT interval and increase the risk of TdP. Because of the potential for TdP, use of fluvoxamine with thioridazine is contraindicated. In addition, although fluvoxamine is not known to inhibit CYP2D6 significantly, fluvoxamine has been reported to elevate serum concentrations of both thioridazine and mesoridazine by roughly 3-fold, probably due to fluvoxamine inhibition of CYP2C19 and CYP2D6. Substantial increases in serum thioridazine concentrations may lead to QT prolongation, TdP, and sudden death.
    Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
    Foscarnet: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP. Because of the potential for TdP, use of foscarnet with thioridazine is contraindicated.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Fosphenytoin: (Moderate) Monitor phenytoin concentrations during concomitant therapy with fosphenytoin and phenothiazines; a fosphenytoin dosage decrease may be necessary. Phenothiazines may inhibit the metabolism of fosphenytoin.
    Fostemsavir: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Because of the potential for TdP, use of fostemsavir with thioridazine is contraindicated. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
    Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and thioridazine. Concomitant use of gabapentin with thioridazine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Galantamine: (Moderate) Conventional antipsychotics with significant anticholinergic effects, such thioridazine, are more likely than other conventional antipsychotics to diminish the therapeutic action of galantamine in treating dementia. Use of an alternative antipsychotic should be considered. Galantamine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and exerts its therapeutic effect by improving the availability of acetylcholine. Consider the use of an antipsychotic with less prominent anticholinergic effects.
    Ganirelix: (Moderate) In the absence of relevant data and as a precaution, drugs that cause hyperprolactinemia, such as phenothiazines, should not be administered concomitantly with ganirelix since hyperprolactinemia downregulates the number of pituitary GnRH receptors.
    Gefitinib: (Contraindicated) The concomitant use of gefitinib and thioridazine is contraindicated; exposure to gefitinib may also increase. Thioridazine is a CYP2D6 substrate and gefitinib is a weak-to-moderate CYP2D6 inhibitor. Concomitant use may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as torsades de pointes (TdP)-type arrhythmias. Additionally, gefitinib is metabolized to O-desmethyl gefitinib by CYP2D6 and thioridazine is a CYP2D6 inhibitor. In healthy CYP2D6 poor metabolizers, the concentration of O-desmethyl gefitinib was not measurable and mean exposure to gefitinib was 2-fold higher compared to extensive metabolizers. The impact of CYP2D6 inhibitors on gefitinib pharmacokinetics has not been evaluated; however, the manufacturer recommends precautions based on exposure in patients with poor CYP2D6 metabolism.
    Gemifloxacin: (Contraindicated) Coadministration of thioridazine and gemifloxacin is contraindicated because of the increased risk for QT interval prolongation and torsade de pointes (TdP). Thioridazine is associated with a well-established risk of QT prolongation and TdP. Gemifloxacin may also prolong the QT interval in some patients, with the maximal change in the QTc interval occurring approximately 5 to 10 hours following oral administration.
    Gemtuzumab Ozogamicin: (Contraindicated) Coadministration of gemtuzumab ozogamicin with thioridazine is contraindicated due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Thioridazine is associated with a well-established risk of QT prolongation and TdP.
    Gentamicin: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask vestibular symptoms that are associated with ototoxicity induced by various medications, including the aminoglycosides.
    Gilteritinib: (Contraindicated) Use of gilteritinib with thioridazine is contraindicated because of the potential for torsade de pointes (TdP). Gilteritinib has been associated with QT prolongation. Thioridazine is associated with a well-established risk of QT prolongation and TdP.
    Givosiran: (Contraindicated) Coadministration of givosiran and thioridazine is contraindicated due to the potential for givosiran to enhance the exposure and toxicity of thioridazine. Elevated thioridazine concentrations would be expected to augment the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious cardiac arrhythmias, such as torsade de pointes. Thioridazine is a CYP2D6 substrate. Givosiran may moderately reduce hepatic CYP2D6 enzyme activity because of its pharmacological effects on the hepatic heme biosynthesis pathway.
    Glasdegib: (Contraindicated) Coadministration of glasdegib and thioridazine is contraindicated due to the potential for additive QT prolongation and torsade de pointes (TdP). Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia.
    Glimepiride: (Moderate) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. Also, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure.
    Glimepiride; Rosiglitazone: (Moderate) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. Also, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
    Glipizide: (Moderate) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. Also, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure.
    Glipizide; Metformin: (Moderate) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. Also, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
    Glyburide: (Moderate) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. Also, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure.
    Glyburide; Metformin: (Moderate) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. Also, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
    Goserelin: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of goserelin with thioridazine is contraindicated; the efficacy of goserelin may also be reduced. Thioridazine is associated with a well-established risk of QT prolongation and TdP. Thioridazine is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Androgen deprivation therapy (i.e., goserelin) may also prolong the QT/QTc interval. Thioridazine can also cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; goserelin is a GnRH analog.
    Granisetron: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of thioridazine with granisetron is contraindicated. Thioridazine is associated with a well-established risk of QT prolongation and TdP; granisetron has also been associated with QT prolongation. Thioridazine is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Guaifenesin; Hydrocodone: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking thioridazine. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking thioridazine. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Guaifenesin; Phenylephrine: (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Guanidine: (Minor) Bone marrow suppression is associated with guanidine therapy. Avoid concomitant use of other drugs known to cause bone marrow suppression such as phenothiazines.
    Guselkumab: (Moderate) Monitor for an altered patient response to thioridazine if coadministration with guselkumab is necessary. Guselkumab therapy may restore CYP450 activities to higher levels than pretreatment, leading to increased metabolism of CYP450 substrates as compared to metabolism prior to treatment. While some drug interaction studies determined guselkumab was not likely to promote such interactions, the effect on CYP2D6 was less certain and variable due to the low numbers of subjects studied. Therefore, CYP2D6 substrates with a narrow therapeutic index may have fluctuations in drug levels and therapeutic effect. Thioridazine is a CYP2D6 substrate and narrow therapeutic index drug.
    Halobetasol; Tazarotene: (Moderate) The manufacturer states that tazarotene should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Halogenated Anesthetics: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension, such as halogenated anesthetics.
    Haloperidol: (Contraindicated) Due to the risk for QT prolongation and potential for serious arrhythmias, as well as duplicative antipsychotic effects, the concurrent use of haloperidol with thioridazine is contraindicated. QT prolongation and torsade de pointes have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Thioridazine is associated with an established risk for QT prolongation and torsade de pointes (TdP). Coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Histrelin: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of histrelin with thioridazine is contraindicated; the efficacy of histrelin may also be reduced. Thioridazine is associated with a well-established risk of QT prolongation and TdP and is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. Thioridazine can also cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog.
    Homatropine; Hydrocodone: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking thioridazine. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Hydrocodone: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking thioridazine. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydrocodone; Ibuprofen: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking thioridazine. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking thioridazine. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydromorphone: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydroxychloroquine: (Contraindicated) Avoid concomitant use of thioridazine and hydroxychloroquine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Hydroxyzine: (Contraindicated) Avoid concomitant use of thioridazine and hydroxyzine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Ibuprofen; Oxycodone: (Major) Concomitant use of oxycodone with phenothiazines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with phenothiazines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Monitor for signs of hypotension after starting or titrating the dosage of oxycodone. There is an increased risk of severe hypotension in patients whose ability to maintain blood pressure has already been compromised by concurrent administration of phenothiazines.
    Ibutilide: (Contraindicated) Coadministration of thioridazine and ibutilide is contraindicated. Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated.
    Iloperidone: (Contraindicated) Iloperidone has been associated with QT prolongation. Due to the risk of additive QT prolongation and potential for serious arrhythmias, including torsade de pointes (TdP), the concurrent use of iloperidone and thioridazine is considered contraindicated. In addition, coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Imatinib: (Contraindicated) Imatinib is a mild inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, occurring from elevated serum concentrations of thioridazine.
    Imipramine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension, including tricyclic antidepressants (TCAs). In addition to additive effects on the cardiovascular system, additive anticholinergic effects and sedation may be observed.
    Incretin Mimetics: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
    Indapamide: (Moderate) Indapamide may cause electrolyte disturbances, which may increase the potential for proarrhythmic effects of selected phenothiazines.
    Inotuzumab Ozogamicin: (Contraindicated) Coadministration of inotuzumab ozogamicin with thioridazine is contraindicated due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). Thioridazine is associated with a well-established risk of QT prolongation and TdP. Inotuzumab has also been associated with QT interval prolongation.
    Insulins: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
    Iodixanol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Phenothiazines should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Iohexol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Phenothiazines should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Iomeprol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Phenothiazines should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Iopamidol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Phenothiazines should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Iopromide: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Phenothiazines should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Ioversol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Phenothiazines should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Ipecac: (Major) Phenothiazines, especially in large quantities, can cause a dystonic reaction. Due to the aspiration risk associated with emesis for a person with acute dystonia of the head or neck,avoid emesis induction for overdose cases.
    Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Isocarboxazid: (Moderate) Concurrent use of MAOIs and phenothiazines may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and phenothiazines should be used together cautiously.
    Isoflurane: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension, such as halogenated anesthetics.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Rifamycins can increase the metabolism or reduce the bioavailability of phenothiazines. Dosage increases of phenothiazines may be necessary following the addition of rifampin or another rifamycin.
    Isoniazid, INH; Rifampin: (Major) Rifamycins can increase the metabolism or reduce the bioavailability of phenothiazines. Dosage increases of phenothiazines may be necessary following the addition of rifampin or another rifamycin.
    Isosulfan Blue: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Phenothiazines should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Itraconazole: (Contraindicated) Thioridazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). Itraconazole has also been associated with QT prolongation. Thioridazine is contraindicated for use with other drugs that are known to prolong the QT interval.
    Ivosidenib: (Contraindicated) Coadministration of ivosidenib with thioridazine is contraindicated due to an increased risk of QT prolongation. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
    Kanamycin: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask vestibular symptoms that are associated with ototoxicity induced by various medications, including the aminoglycosides.
    Ketamine: (Moderate) The use of ketamine with other CNS depressants, such as phenothiazines, can potentiate CNS depression and/or increase the risk of developing respiratory depression.
    Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and thioridazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Lansoprazole; Amoxicillin; Clarithromycin: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with clarithromycin which, when combined with a thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Lanthanum Carbonate: (Major) Oral compounds known to interact with antacids, like phenothiazines, should not be taken within 2 hours of dosing with lanthanum carbonate. If these agents are used concomitantly, space the dosing intervals appropriately. Monitor serum concentrations and clinical condition.
    Lapatinib: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of lapatinib with thioridazine is contraindicated. Thioridazine is associated with a well-established risk of QT prolongation and TdP. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and TdP have been reported in postmarketing experience with lapatinib.
    Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and thioridazine. Concurrent use may result in additive CNS depression.
    Lefamulin: (Contraindicated) Coadministration of thioridazine with lefamulin is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Thioridazine is associated with a well-established risk of QT prolongation and TdP. 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.
    Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and phenothiazines. Dosage adjustments of lemborexant and the phenothiazine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
    Lenvatinib: (Contraindicated) Because of the potential for torsades de pointes (TdP), use of thioridazine with lenvatinib is contraindicated. Thioridazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP) and is contraindicated for use with other drugs that are known to prolong the QT interval. Prolongation of the QT interval has also been reported with lenvatinib therapy.
    Letermovir: (Major) Concurrent administration of letermovir and thioridazine is not recommended. Use of these drugs together may decrease letermovir plasma concentrations, resulting in a potential loss of letermovir efficacy.
    Leuprolide: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of leuprolide with thioridazine is contraindicated; the efficacy of leuprolide may also be reduced. Thioridazine is associated with a well-established risk of QT prolongation and TdP and is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval. Thioridazine can also cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
    Leuprolide; Norethindrone: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of leuprolide with thioridazine is contraindicated; the efficacy of leuprolide may also be reduced. Thioridazine is associated with a well-established risk of QT prolongation and TdP and is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval. Thioridazine can also cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
    Levodopa: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
    Levofloxacin: (Contraindicated) Avoid concomitant use of thioridazine and levofloxazin due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and thioridazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Levonorgestrel; Ethinyl Estradiol: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Levorphanol: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Reduce the initial dose of levorphanol by approximately 50% or more. Educate patients about the risks and symptoms of excessive CNS depression.
    Lidocaine; Epinephrine: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
    Linagliptin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
    Linagliptin; Metformin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
    Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Lithium: (Contraindicated) Lithium has been associated with QT prolongation. Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Because of the potential for TdP, use of lithium with thioridazine is contraindicated. Additionally, some atypical antipsychotics are considered first-line adjunctive therapy to mood stabilizers such as lithium. However, it is advisable to monitor patients for neurotoxicity during co-administration. Neuroleptic malignant syndrome (NMS) has been observed occasionally during concurrent use of lithium and either atypical or conventional antipsychotics. Additive extrapyramidal effects have also been noted. Early case reports described an encephalopathic syndrome consisting of delirium, tremulousness, dyskinesia, seizures, leukocytosis, weakness, hyperpyrexia, confusion, extrapyramidal symptoms, elevations in laboratory values (e.g., liver function tests, blood urea nitrogen, fasting blood sugar) and, in some cases, irreversible brain damage, during use of lithium and conventional antipsychotics, particularly haloperidol. Subsequent rare reports of NMS or NMS-like reactions have been described during co-administration of lithium and atypical antipsychotics (e.g., aripiprazole, risperidone, olanzapine, clozapine). Following resolution of NMS, there are isolated instances of re-emergence of symptoms following re-initiation of lithium as monotherapy. Lithium may be a risk factor for antipsychotic-induced NMS; however, this hypothesis has not been confirmed. In many reported cases, confounding factors have been present (e.g., previous history of NMS, high dose therapy). The ability of antipsychotics alone to precipitate NMS and the rarity of the condition further complicate assessment of lithium as a risk factor.
    Lofexidine: (Contraindicated) Concomitant use of lofexidine and thioridazine is contraindicated due to the potential for additive QT prolongation and torsade de pointes (TdP). Lofexidine is a CYP2D6 substrate that prolongs the QT interval. In addition, there are postmarketing reports of TdP. Thioridazine is a CYP2D6 inhibitor and is associated with a well-established risk of QT prolongation and TdP.
    Loperamide: (Contraindicated) Avoid concomitant use of loperamide and thioridazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Loperamide; Simethicone: (Contraindicated) Avoid concomitant use of loperamide and thioridazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Lopinavir; Ritonavir: (Contraindicated) Coadministration of lopinavir with thioridazine is contraindicated due to the potential for additive QT prolongation. Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Lopinavir is associated with QT prolongation. (Moderate) Close clinical monitoring is recommended during coadministration; thioridazine dose reductions may be required. The plasma concentrations of thioridazine may be elevated when administered concurrently with ritonavir. Elevated levels of thioridazine may result in prolongation of the QTc interval and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as torsades de pointes.
    Lorazepam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
    Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Loxapine: (Moderate) Caution is advisable during concurrent use of antipsychotics, including loxapine and thioridazine. Coadministration may increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, and seizures.
    Lumateperone: (Moderate) Coadministration of antipsychotics, such as lumateperone and thioridazine, may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from antipsychotic combinations has not been established and data are very limited, the risk may be increased during combined use versus use of an antipsychotic alone.
    Lurasidone: (Major) Similar to other antipsychotics, lurasidone administration has been associated with drowsiness, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. The risk of these adverse effects may be increased during concurrent use of lurasidone with other antipsychotics. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Macimorelin: (Contraindicated) Because of the potential for TdP, use of macimorelin with thioridazine is contraindicated. Discontinue use of thioridazine and allow a sufficient washout period before administering macimorelin. Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, or cause orthostatic hypotension. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval.
    Maprotiline: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Maprotiline is rarely associated with QT prolongation. Additionally, additive toxicities (e.g., cardiac effects, CNS effects, orthostatic hypotension, and antimuscarinic effects) may occur because maprotiline and thioridazine are both metabolized via similar pathways (CYP2D6), have structural similarities, and produce similar pharmacologic effects (antimuscarinic activity). Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
    Meclizine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with meclizine. Patients should be informed to read non-prescription product labels carefully for additional interacting motion sickness medications.
    Mefloquine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with mefloquine which, when combined with thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Meglitinides: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
    Melatonin: (Moderate) Monitor for unusual drowsiness and excessive duration during coadministration of melatonin and phenothiazines due to the risk for additive CNS depression.
    Meperidine: (Major) Hypotension, respiratory and/or CNS depression may occur if meperidine is used concomitantly with CNS depressants, including thioridazine. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Meperidine; Promethazine: (Contraindicated) Due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of promethazine and thioridazine is considered contraindicated. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes. (Major) Hypotension, respiratory and/or CNS depression may occur if meperidine is used concomitantly with CNS depressants, including thioridazine. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Meprobamate: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered with other CNS depressant drugs and they should be used cautiously with anxiolytic, sedative, and hypnotics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of hypnotics and other CNS depressants than with use of a hypnotic alone.
    Mequinol; Tretinoin: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Mestranol; Norethindrone: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Metaxalone: (Moderate) Phenothiazines can potentiate the CNS-depressant action of skeletal muscle relaxants like metaxalone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects.
    Metformin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
    Metformin; Repaglinide: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
    Metformin; Rosiglitazone: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
    Metformin; Saxagliptin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
    Metformin; Sitagliptin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
    Methadone: (Contraindicated) Because of the potential for torsades de pointes (TdP), concurrent use of methadone and thioridazine is contraindicated. Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP) and is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Methadone is considered to be associated with an increased risk for QT prolongation and torsades de pointes (TdP), especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). Laboratory studies, both in vivo and in vitro, have demonstrated that methadone inhibits cardiac potassium channels and prolongs the QT interval. 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.
    Methocarbamol: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of methocarbamol and phenothiazines due to the risk for additive CNS depression; dosage adjustments may be necessary.
    Methohexital: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Methoxsalen: (Moderate) Use methoxsalen and phenothiazines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Methsuximide: (Major) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added.
    Methyclothiazide: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Metoclopramide: (Contraindicated) Avoid metoclopramide in patients receiving phenothiazine antipsychotics due to potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Also avoid the use of metoclopramide with phenothiazine antiemetics if possible due to these risks. Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. Discontinue these medications at the first signs of dyskinesia. Metoclopramide is a central dopamine antagonist and may cause EPS (e.g., acute dystonic reactions, pseudo-parkinsonism, akathisia, tardive dyskinesia). Tardive dyskinesia (TD) is a syndrome of potentially irreversible and disfiguring involuntary movements of the face or tongue, and sometimes of the trunk and/or extremities. Movements may be choreoathetotic in appearance. Phenothiazines are also central dopamine antagonists. In addition, both phenothiazines and metoclopramide can cause sedation, seizures, or increased prolactin levels.
    Metolazone: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Metoprolol: (Moderate) Monitor for metoprolol-related adverse reactions, including bradycardia and hypotension, during coadministration with thioridazine. Concomitant use may increase metoprolol serum concentrations which would decrease the cardioselectivity of metoprolol. Metoprolol is a CYP2D6 substrate and thioridazine is a CYP2D6 inhibitor.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines. (Moderate) Monitor for metoprolol-related adverse reactions, including bradycardia and hypotension, during coadministration with thioridazine. Concomitant use may increase metoprolol serum concentrations which would decrease the cardioselectivity of metoprolol. Metoprolol is a CYP2D6 substrate and thioridazine is a CYP2D6 inhibitor.
    Metronidazole: (Contraindicated) Avoid concomitant use of metronidazole and thioridazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Metyrapone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as phenothiazines, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Metyrosine: (Moderate) Because it also blocks central dopamine receptors, metyrosine should be avoided or used cautiously in patients receiving a phenothiazine to minimize the risk of additive adverse CNS effects. A dose reduction may be required if combination therapy is necessary.
    Mexiletine: (Moderate) Mexiletine is significantly metabolized by CYP2D6 isoenzymes. CYP2D6 inhibitors, such as thioridazine, could theoretically impair mexiletine metabolism; the clinical significance of such interactions is unknown.
    Midazolam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
    Midostaurin: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of midostaurin with thioridazine is contraindicated. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Thioridazine is associated with a well-established risk of QT prolongation and TdP.
    Mifepristone: (Contraindicated) Avoid concomitant use of thioridazine and mifepristone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Miglitol: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
    Minocycline: (Minor) Injectable minocycline contains magnesium sulfate heptahydrate. Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as phenothiazines. Caution should be exercised when using these agents concurrently.
    Mirabegron: (Contraindicated) Mirabegron is a moderate inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, due to elevated serum concentrations of thioridazine.
    Mirtazapine: (Contraindicated) Avoid concomitant use of thioridazine and mirtazapine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Mitotane: (Moderate) Mitotane can cause sedation, lethargy, vertigo, and other CNS side effects. Concomitant administration of mitotane and CNS depressants, including opiate agonists, may cause additive CNS effects.
    Mobocertinib: (Contraindicated) Avoid concomitant use of mobocertinib and thioridazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Molindone: (Major) Close monitoring is advisable during concurrent use of molindone with other antipsychotics. Because molindone shares certain pharmacological properties with other antipsychotics, additive cardiac effects (e.g., hypotension), CNS effects (e.g., drowsiness), or anticholinergic effects (e.g., constipation, xerostomia) may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
    Monoamine oxidase inhibitors: (Moderate) Concurrent use of MAOIs and phenothiazines may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and phenothiazines should be used together cautiously.
    Morphine: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. For extended-release morphine tablets, start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of excessive CNS depression.
    Morphine; Naltrexone: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. For extended-release morphine tablets, start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of excessive CNS depression.
    Moxifloxacin: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with moxifloxacin which, when combined with a thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Nabilone: (Moderate) Concomitant use of nabilone with other CNS depressants, including phenothiazines, can potentiate the effects of nabilone on respiratory depression.
    Nadolol: (Moderate) Concomitant treatment with nadolol and phenothiazines, especially in large doses, can have an additive hypotensive effect.
    Nafarelin: (Moderate) Antipsychotics may cause hyperprolactinemia and should not be administered concomitantly with nafarelin since hyperprolactinemia down-regulates the number of pituitary GnRH receptors.
    Nalbuphine: (Moderate) Concomitant use of nalbuphine with other CNS depressants, such as phenothiazines, can potentiate the effects of nalbuphine on respiratory depression, CNS depression, and sedation.
    Naltrexone: (Moderate) Patients receiving phenothiazines and naltrexone concomitantly have had symptoms of somnolence and lethargy.
    Nebivolol: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with thioridazine. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as thioridazine, 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 thioridazine. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as thioridazine, 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.
    Nilotinib: (Contraindicated) Nilotinib prolongs the QT interval. Because of the potential for torsade de pointes, use of thioridazine with nilotinib is contraindicated.
    Nirmatrelvir; Ritonavir: (Moderate) Close clinical monitoring is recommended during coadministration; thioridazine dose reductions may be required. The plasma concentrations of thioridazine may be elevated when administered concurrently with ritonavir. Elevated levels of thioridazine may result in prolongation of the QTc interval and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as torsades de pointes.
    Nitroglycerin: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as phenothiazines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with phenothiazines.
    Non-Ionic Contrast Media: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Phenothiazines should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Norepinephrine: (Minor) The alpha-adrenergic effects of norepinephrine can be blocked during concurrent administration of phenothiazines. This blockade can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking phenothiazines can possibly have reduced pressor response to ephedrine, phenylephrine, or norepinephrine, but these drugs are preferred over epinephrine if a vasopressor agent is required. According to the manufacturers of the various phenothiazines, norepinephrine or phenylephrine may be used if a vasopressor is needed.
    Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Norethindrone; Ethinyl Estradiol: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Norgestimate; Ethinyl Estradiol: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Nortriptyline: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension, including tricyclic antidepressants (TCAs). In addition to additive effects on the cardiovascular system, additive anticholinergic effects and sedation may be observed.
    Octreotide: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Because of the potential for TdP, use of octreotide with thioridazine is contraindicated. In addition, antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Other drugs that also decrease GI motility, such as thioridazine, may produce additive effects with antidiarrheals if used concomitantly.
    Ofloxacin: (Contraindicated) Avoid concomitant use of thioridazine and ofloxacin due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Olanzapine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes and is contraindicated with other drugs that prolong the QTc interval. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. In addition, coadministration may increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, or seizures. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Olanzapine; Fluoxetine: (Contraindicated) Fluoxetine is contraindicated for use with some phenothiazine antipsychotics including thioridazine. Thioridazine has an established risk of QT prolongation and torsade de pointes (TdP), and post-marketing reports suggest a possible risk of QT prolongation and TdP with fluoxetine. In addition, the metabolism of thioridazine may be decreased during use of CYP2D6 inhibitors such as fluoxetine. Due to the long half-life of fluoxetine and its active metabolite, thioridazine should not be initiated within 5 weeks after discontinuing fluoxetine. Decreased metabolism of this CYP2D6 substrates by fluoxetine may also lead to arrhythmias or other clinically important adverse reactions such as extrapyramidal symptoms. (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes and is contraindicated with other drugs that prolong the QTc interval. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. In addition, coadministration may increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, or seizures. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Olanzapine; Samidorphan: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes and is contraindicated with other drugs that prolong the QTc interval. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. In addition, coadministration may increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, or seizures. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Oliceridine: (Major) Concomitant use of oliceridine with thioridazine may cause excessive sedation and somnolence. Limit the use of oliceridine with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and thioridazine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and thioridazine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If thioridazine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and thioridazine is a moderate CYP2D6 inhibitor.
    Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Close clinical monitoring is recommended during coadministration; thioridazine dose reductions may be required. The plasma concentrations of thioridazine may be elevated when administered concurrently with ritonavir. Elevated levels of thioridazine may result in prolongation of the QTc interval and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as torsades de pointes.
    Omeprazole; Amoxicillin; Rifabutin: (Major) Rifamycins can increase the metabolism or reduce the bioavailability of phenothiazines. Dosage increases of phenothiazines may be necessary following the addition of rifampin or another rifamycin.
    Ondansetron: (Contraindicated) Avoid concomitant use of thioridazine and ondansetron due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose.
    Oritavancin: (Moderate) Thioridazine is metabolized by CYP2D6; oritavancin is a weak CYP2D6 inducer. Plasma concentrations and efficacy of thioridazine may be reduced if these drugs are administered concurrently.
    Orphenadrine: (Moderate) Additive anticholinergic effects may be seen when thioridazine is used concomitantly with other drugs having antimuscarinic activity such as orphenadrine. Additive sedation may also occur.
    Osilodrostat: (Contraindicated) Coadministration of thioridazine with osilodrostat is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Thioridazine is associated with a well-established risk of QT prolongation and TdP. Osilodrostat is associated with dose-dependent QT prolongation.
    Osimertinib: (Contraindicated) Concomitant use of osimertinib and thioridazine is contraindicated because there is an increased risk of QT prolongation and torsade de pointes (TdP). Osimertinib causes concentration dependent prolongation of the QT interval at recommended dosing. In addition, thioridazine is associated with a well-established risk of QT prolongation and TdP. Coadministration may further increase the risk of QT prolongation.
    Oxaliplatin: (Contraindicated) Coadministration of thioridazine with oxaliplatin is contraindicated due to the risk of additive QT prolongation and torsade de pointes (TdP). Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Oxazepam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
    Oxycodone: (Major) Concomitant use of oxycodone with phenothiazines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with phenothiazines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Monitor for signs of hypotension after starting or titrating the dosage of oxycodone. There is an increased risk of severe hypotension in patients whose ability to maintain blood pressure has already been compromised by concurrent administration of phenothiazines.
    Oxymorphone: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Reduce the initial oxymorphone dosage by 1/3 to 1/2. Educate patients about the risks and symptoms of excessive CNS depression.
    Ozanimod: (Contraindicated) Coadministration of thioridazine with ozanimod is contraindicated due to the risk for additive QT prolongation and torsade de pointes (TdP). Thioridazine is associated with a well-established risk of QT prolongation and TdP. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
    Pacritinib: (Contraindicated) Avoid concomitant use of pacritinib and thioridazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Paliperidone: (Contraindicated) Thioridazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP) and is contraindicated for use with other drugs that are known to prolong the QT interval, including paliperidone. In addition, coadministration of antipsychotics may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Panobinostat: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of thioridazine with panobinostat is contraindicated. 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. Thioridazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP and is contraindicated for use with other drugs that are known to prolong the QT interval.
    Paromomycin: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask vestibular symptoms that are associated with ototoxicity induced by various medications, including the aminoglycosides.
    Paroxetine: (Contraindicated) Coadministration of thioridazine and paroxetine is contraindicated due to the potential for increased thioridazine exposure. Increased plasma concentrations of thioridazine are expected to increase the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as torsade de pointes type arrhythmias. Thioridazine is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor.
    Pasireotide: (Contraindicated) Because of the potential for torsades de pointes (TdP), use of pasireotide and thioridazine is contraindicated. Thioridazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP) and is contraindicated for use with other drugs that are known to prolong the QT interval. Coadministration of pasireotide and drugs that prolong the QT interval may have additive effects on the prolongation of the QT interval.
    Pazopanib: (Contraindicated) Pazopanib has been reported to prolong the QT interval. Because of the potential for torsade de pointes (TdP), use of tthioridazine with pazopanib is contraindicated.
    Peginterferon Alfa-2b: (Contraindicated) Peginterferon Alfa-2b is a mild inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, occurring from elevated serum concentrations of thioridazine.
    Pentamidine: (Contraindicated) Both thioridazine and pentamidine have been associated with QT prolongation. Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension, including pentamidine.
    Pentazocine: (Moderate) Concomitant use of pentazocine with other CNS depressants, such as phenothiazines, can potentiate respiratory depression, CNS depression, and sedation. Pentazocine should be used cautiously with phenothiazines.
    Pentazocine; Naloxone: (Moderate) Concomitant use of pentazocine with other CNS depressants, such as phenothiazines, can potentiate respiratory depression, CNS depression, and sedation. Pentazocine should be used cautiously with phenothiazines.
    Pentobarbital: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Perampanel: (Moderate) Co-administration of perampanel with CNS depressants, including ethanol, may increase CNS depression. The combination of perampanel (particularly at high doses) with ethanol has led to decreased mental alertness and ability to perform complex tasks (such as driving), as well as increased levels of anger, confusion, and depression; similar reactions should be expected with concomitant use of other CNS depressants, such as phenothiazines.
    Perphenazine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP) and is contraindicated with other drugs that can prolong the QTc interval. Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation and TdP. In addition, coadministration may increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, or seizures.
    Perphenazine; Amitriptyline: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP) and is contraindicated with other drugs that can prolong the QTc interval. Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation and TdP. In addition, coadministration may increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, or seizures. (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension, including tricyclic antidepressants (TCAs). In addition to additive effects on the cardiovascular system, additive anticholinergic effects and sedation may be observed.
    Phenelzine: (Moderate) Concurrent use of MAOIs and phenothiazines may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and phenothiazines should be used together cautiously.
    Phenobarbital: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Phentermine; Topiramate: (Moderate) Monitor for unusual drowsiness and excess sedation during coadministration of phenothiazines and topiramate due to the risk for additive CNS depression.
    Phenylephrine: (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Phenytoin: (Moderate) Monitor phenytoin concentrations during concomitant therapy with phenytoin and phenothiazines; a phenytoin dosage decrease may be necessary. Phenothiazines may inhibit the metabolism of phenytoin.
    Photosensitizing agents (topical): (Moderate) Phenothiazines may increase the photosensitizing effects of photosensitizing agents used in photodynamic therapy. Patients should limit ultra-violet exposure.
    Pilocarpine: (Moderate) Avoid using pilocarpine in combination with other drugs known to have anticholinergic effects as the therapeutic efficacy of either agent may be reduced.
    Pimavanserin: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Because pimavanserin causes QT prolonging effects that may be additive to those of thioridazine, coadministration is contraindicated. Also, the manufacturer of pimavanserin recommends avoiding use of moderate inducers of CYP3A4, such as thioridazine, with pimavanserin because of a reduction in pimavanserin exposure, which has the potential to reduce the effectiveness of the drug.
    Pimozide: (Contraindicated) Pimozide and thioridazine are both associated with a well-established risk of QT prolongation and torsade de pointes (TdP); therefore, concurrent use is contraindicated. Concurrent use of pimozide with phenothiazines may also increase the risk of serious adverse effects such as extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures.
    Pindolol: (Contraindicated) The manufacturer of thioridazine considers pindolol to be contraindicated for use with thioridazine. Pindolol appears to inhibit the hepatic metabolism of phenothiazine neuroleptics, and phenothiazines appear to decrease the hepatic metabolism of these two beta-blockers. Increased serum concentrations and pharmacologic effects (e.g., cardiac, CNS, hypotension) of either drug may occur. It is not known if other hepatically-metabolized beta-blockers (e.g., carvedilol, metoprolol, timolol) interact with the phenothiazines in this manner. Beta-blockers with greater renal elimination (e.g., atenolol, nadolol) are less likely to have an interaction with phenothiazines.
    Pioglitazone: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
    Pioglitazone; Glimepiride: (Moderate) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. Also, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
    Pioglitazone; Metformin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia.
    Pitolisant: (Contraindicated) Coadministration of thioridazine with pitolisant is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Thioridazine is associated with a well-established risk of QT prolongation and TdP. Pitolisant prolongs the QT interval.
    Plazomicin: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask vestibular symptoms that are associated with ototoxicity induced by various medications, including the aminoglycosides.
    Ponesimod: (Contraindicated) Coadministration of thioridazine with ponesimod is contraindicated due to the risk for additive QT prolongation and torsade de pointes (TdP). Thioridazine is associated with a well-established risk of QT prolongation and TdP. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
    Porfimer: (Major) Avoid coadministration of porfimer with phenothiazines due to the risk of increased photosensitivity. Porfimer is a light-activated drug used in photodynamic therapy; all patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like phenothiazines may increase the risk of a photosensitivity reaction.
    Posaconazole: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with posaconazole which, when combined with thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Pramipexole: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and pramipexole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. In addition, coadministration may result in additive sedation.
    Pramlintide: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
    Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and thioridazine. Concomitant use of pregabalin with thioridazine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Prilocaine; Epinephrine: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
    Primaquine: (Contraindicated) Primaquine has the potential to prolong the QT interval. Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Because of the potential for TdP, use of primaquine with thioridazine is contraindicated.
    Primidone: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Procainamide: (Contraindicated) Because of the potential for torsade de pointes (TdP), concurrent use of procainamide and thioridazine is contraindicated. Class IA antiarrhythmics and thioridazine are associated with a well-established risk of QT prolongation and TdP. Thioridazine is considered contraindicated for use with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Procarbazine: (Moderate) CNS depressants, such as phenothiazines, can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
    Prochlorperazine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes and is considered contraindicated with other drugs that may cause QT prolongation such as prochlorperazine. In addition, coadministration of antipsychotics may increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, or seizures.
    Promethazine: (Contraindicated) Due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of promethazine and thioridazine is considered contraindicated. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes.
    Promethazine; Dextromethorphan: (Contraindicated) Due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of promethazine and thioridazine is considered contraindicated. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes.
    Promethazine; Phenylephrine: (Contraindicated) Due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of promethazine and thioridazine is considered contraindicated. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes. (Moderate) Other non-cardiovascular drugs with alpha-blocking activity such as phenothiazines, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
    Propafenone: (Contraindicated) Avoid concomitant use of thioridazine and propafenone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Propranolol: (Contraindicated) The manufacturer of thioridazine considers propranolol to be contraindicated for use with thioridazine. Propranolol appears to inhibit the hepatic metabolism of phenothiazine neuroleptics, and phenothiazines appear to decrease the hepatic metabolism of these two beta-blockers. Increased serum concentrations and pharmacologic effects (e.g., cardiac, CNS, hypotension) of either drug may occur. It is not known if other hepatically-metabolized beta-blockers (e.g., carvedilol, metoprolol, timolol) interact with the phenothiazines in this manner. Beta-blockers with greater renal elimination (e.g., atenolol, nadolol) are less likely to have an interaction with phenothiazines.
    Propranolol; Hydrochlorothiazide, HCTZ: (Contraindicated) The manufacturer of thioridazine considers propranolol to be contraindicated for use with thioridazine. Propranolol appears to inhibit the hepatic metabolism of phenothiazine neuroleptics, and phenothiazines appear to decrease the hepatic metabolism of these two beta-blockers. Increased serum concentrations and pharmacologic effects (e.g., cardiac, CNS, hypotension) of either drug may occur. It is not known if other hepatically-metabolized beta-blockers (e.g., carvedilol, metoprolol, timolol) interact with the phenothiazines in this manner. Beta-blockers with greater renal elimination (e.g., atenolol, nadolol) are less likely to have an interaction with phenothiazines. (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Protriptyline: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension, including tricyclic antidepressants (TCAs). In addition to additive effects on the cardiovascular system, additive anticholinergic effects and sedation may be observed.
    Pseudoephedrine; Triprolidine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as triprolidine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Pyrilamine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as pyrilamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Quazepam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
    Quetiapine: (Contraindicated) Thioridazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP) and is contraindicated for use with other drugs that are known to prolong the QT interval, such as quetiapine. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. In addition, co-administration of quetiapine with a phenothiazine may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. Further, thioridazine increases the oral clearance of quetiapine by about 65%.
    Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Quinidine: (Contraindicated) Because of the potential for torsade de pointes (TdP), concurrent use of quinidine and thioridazine is contraindicated. Class IA antiarrhythmics and thioridazine are associated with a well-established risk of QT prolongation and TdP. Thioridazine is considered contraindicated for use with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Quinine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Thioridazine is considered contraindicated for use with quinine, which when combined with thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Ranolazine: (Contraindicated) Coadministration is contraindicated. 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. Because of the potential for TdP, coadministration is contraindicated. Additionally, thioridazine is an inhibitor of CYP2D6, and ranolazine is metabolized, to a lesser extent, by CYP2D6. Thioridazine may increase the plasma concentrations of ranolazine.
    Rasagiline: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and rasagiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic to the phenothiazine, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
    Relugolix: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of relugolix with thioridazine is contraindicated. Thioridazine is associated with a well-established risk of QT prolongation and TdP and is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
    Relugolix; Estradiol; Norethindrone acetate: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of relugolix with thioridazine is contraindicated. Thioridazine is associated with a well-established risk of QT prolongation and TdP and is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
    Remifentanil: (Moderate) Phenothiazines can potentiate the CNS depressant action of other drugs such as opiate agonists. A dose reduction of one or both drugs may be warranted.
    Remimazolam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
    Ribociclib: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of ribociclib with thioridazine is contraindicated. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Thioridazine is associated with a well-established risk of QT prolongation and TdP. Concomitant use may increase the risk for QT prolongation.
    Ribociclib; Letrozole: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of ribociclib with thioridazine is contraindicated. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Thioridazine is associated with a well-established risk of QT prolongation and TdP. Concomitant use may increase the risk for QT prolongation.
    Rifabutin: (Major) Rifamycins can increase the metabolism or reduce the bioavailability of phenothiazines. Dosage increases of phenothiazines may be necessary following the addition of rifampin or another rifamycin.
    Rifampin: (Major) Rifamycins can increase the metabolism or reduce the bioavailability of phenothiazines. Dosage increases of phenothiazines may be necessary following the addition of rifampin or another rifamycin.
    Rifamycins: (Major) Rifamycins can increase the metabolism or reduce the bioavailability of phenothiazines. Dosage increases of phenothiazines may be necessary following the addition of rifampin or another rifamycin.
    Rifapentine: (Major) Rifamycins can increase the metabolism or reduce the bioavailability of phenothiazines. Dosage increases of phenothiazines may be necessary following the addition of rifampin or another rifamycin.
    Rilpivirine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and TdP. Thioridazine is considered contraindicated for use along with rilpivirine which, when combined with thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Risperidone: (Contraindicated) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer primarily in the overdosage setting. However, due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of risperidone and thioridazine is considered contraindicated.
    Ritonavir: (Moderate) Close clinical monitoring is recommended during coadministration; thioridazine dose reductions may be required. The plasma concentrations of thioridazine may be elevated when administered concurrently with ritonavir. Elevated levels of thioridazine may result in prolongation of the QTc interval and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as torsades de pointes.
    Rivastigmine: (Moderate) Conventional antipsychotics with significant anticholinergic effects, such as chlorpromazine and thioridazine, are more likely than other conventional antipsychotics to diminish the therapeutic action of rivastigmine, and use of an alternative antipsychotic should be considered. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and exerts its therapeutic effect by improving the availability of acetylcholine. Consider the use of an antipsychotic with less prominent anticholinergic effects.
    Rolapitant: (Contraindicated) Rolapitant is a moderate inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, due to elevated serum concentrations of thioridazine. The CYP2D6 inhibitory effect of rolapitant is expected to persist beyond 28 days for an unknown duration.
    Romidepsin: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP) and is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Romidepsin has been reported to prolong the QT interval. Because of the potential for TdP, use of romidepsin with thioridazine is contraindicated.
    Ropinirole: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and ropinirole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
    Rosiglitazone: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
    Rotigotine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. In addition, coadministration may result in additive sedation.
    Safinamide: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine if appropriate. If coadministration cannot be avoided, monitor for changes in movements, moods, or behaviors.
    Saquinavir: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Thioridazine is considered contraindicated for use along with saquinavir which, when combined with thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Sarilumab: (Moderate) Monitor for an altered patient response to thioridazine if coadministration with sarilumab is necessary. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as thioridazine, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Thioridazine is a CYP2D6 substrate and narrow therapeutic index drug.
    Saxagliptin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
    Secobarbital: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Secukinumab: (Moderate) Monitor for an altered patient response to thioridazine if coadministration with secukinumab is necessary. Secukinumab therapy may restore CYP450 activities to higher levels than pretreatment, leading to increased metabolism of CYP450 substrates as compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index may have fluctuations in drug levels and therapeutic effect. Thioridazine is a CYP2D6 substrate and narrow therapeutic index drug.
    Segesterone Acetate; Ethinyl Estradiol: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Selegiline: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of phenothiazines and selegiline due to the risk for additive CNS depression. It is also possible that dopamine antagonists, such as phenothiazines, could diminish the effectiveness of selegiline.
    Selpercatinib: (Contraindicated) Coadministration of thioridazine with selpercatinib is contraindicated due to the risk for additive QT prolongation and torsade de pointes (TdP). Thioridazine is associated with a well-established risk of QT prolongation and TdP. Selpercatinib can cause concentration-dependent interval prolongation.
    Sertraline: (Contraindicated) Coadministration of thioridazine and sertraline is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Thioridazine is associated with a well-established risk of QT prolongation and TdP and is considered contraindicated for use along with agents associated with QT interval and TdP. QT prolongation and TdP have been reported during postmarketing use of sertraline. Additionally, thioridazine is a CYP2D6 substrate and use with a CYP2D6 inhibitor such as sertraline may increase the risk of thioridazine-induced arrhythmias.
    Sevoflurane: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension, such as halogenated anesthetics.
    SGLT2 Inhibitors: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted.
    Siltuximab: (Moderate) Monitor for an altered patient response to thioridazine if coadministration with siltuximab is necessary. Inhibition of IL-6 signaling by siltuximab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as thioridazine, may have fluctuations in drug levels and therapeutic effect when siltuximab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping siltuximab. In vitro, siltuximab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Thioridazine is a CYP2D6 substrate and narrow therapeutic index drug.
    Simvastatin; Sitagliptin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
    Siponimod: (Contraindicated) Concomitant use of siponimod and thioridazine is contraindicated due to the potential for additive QT prolongation. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes.
    Sitagliptin: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
    Sodium Oxybate: (Major) Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with phenothiazines.
    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 antipsychotics, as these drugs may increase the risk of water retention and/or electrolyte imbalance.
    Sodium Stibogluconate: (Contraindicated) Avoid concomitant use of sodium stibogluconate and thioridazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Solifenacin: (Contraindicated) Because of the potential for torsades de pointes (TdP), concurrent use of solifenacin and thioridazine is contraindicated. Solifenacin has been associated dose-dependent prolongation of the QT interval. TdP has been reported with post-marketing use, although causality was not determined. Thioridazine is associated with a well-established risk of QT prolongation and TdP. Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Sorafenib: (Contraindicated) Because of the potential for TdP, use of sorafenib with thioridazine is contraindicated. Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Sorafenib has also been associated with QT prolongation.
    Sotalol: (Contraindicated) Avoid concomitant use of thioridazine and sotalol due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Streptomycin: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask vestibular symptoms that are associated with ototoxicity induced by various medications, including the aminoglycosides.
    Sufentanil: (Moderate) Phenothiazines can potentiate the CNS depressant action of other drugs such as opiate agonists. A dose reduction of one or both drugs may be warranted.
    Sulfonylureas: (Moderate) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. Also, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure.
    Sunitinib: (Contraindicated) Because of the potential for torsades de pointes (TdP), use of sunitinib with thioridazine is contraindicated. Sunitinib can prolong the QT interval. Thioridazine is associated with a well-established risk of QT prolongation and TdP. Coadministration may result in additive effects on the QT interval and further increase the risk of TdP.
    Tacrolimus: (Contraindicated) The use of thioridazine with tacrolimus is contraindicated due to the risk for QT prolongation and torsade de pointes (TdP). Thioridazine is also associated with a well-established risk of QT prolongation and TdP. Tacrolimus has been associated with QT prolongation.
    Tamoxifen: (Contraindicated) Avoid concomitant use of thioridazine and tamoxifen due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Tamsulosin: (Moderate) Use caution when administering tamsulosin with a CYP2D6 inhibitor such as thioridazine. 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) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Tazarotene: (Moderate) The manufacturer states that tazarotene should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Telavancin: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with telavancin which, when combined with thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Telithromycin: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Thioridazine is considered contraindicated for use along with telithromycin which, when combined with thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Temazepam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
    Terbinafine: (Contraindicated) Coadministration of terbinafine, a CYP2D6 inhibitor, and thioridazine, a CYP2D6 substrate, is contraindicated, as concurrent use may result in increased exposure to thioridazine. Elevated thioridazine concentrations would be expected to augment the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as torsade de pointes.
    Terfenadine: (Contraindicated) Use together is contradindicated due to the risk for QT prolongation and torsade de pointes (TdP). Both thioridazine and terfenadine are associated with a well-established risk of QT prolongation and TdP.
    Tetrabenazine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Because of the potential for TdP, use of tetrabenazine with thioridazine is contraindicated.
    Thalidomide: (Major) Avoid the concomitant use of thalidomide with opiate agonists; antihistamines; antipsychotics; anxiolytics, sedatives, and hypnotics; and other central nervous system depressants due to the potential for additive sedative effects.
    Thiazide diuretics: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Thiazolidinediones: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
    Thiothixene: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine antipsychotics. Thiothixene use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of phenothiazines and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase.
    Tiagabine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added.
    Tobacco: (Major) Advise patients to avoid smoking tobacco while taking phenothiazines. Tobacco smoking may increase the clearance of phenothiazines, which may reduce their efficacy.
    Tobramycin: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask vestibular symptoms that are associated with ototoxicity induced by various medications, including the aminoglycosides.
    Tocilizumab: (Moderate) Monitor for an altered patient response to thioridazine if coadministration with tocilizumab is necessary. Inhibition of IL-6 signaling by tocilizumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as thioridazine, may have fluctuations in drug levels and therapeutic effect when tocilizumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping tocilizumab. In vitro, tocilizumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Thioridazine is a CYP2D6 substrate and narrow therapeutic index drug.
    Tolazamide: (Moderate) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. Also, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure.
    Tolbutamide: (Moderate) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted. Also, concomitant use may increase the risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure.
    Tolterodine: (Contraindicated) Thioridazine is considered contraindicated for use along with tolterodine. Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Coadministration wirh tolterodine may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. Additionally, additive anticholinergic effects may also be seen when phenothiazines are used concomitantly with antimuscarinic agents. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
    Topiramate: (Moderate) Monitor for unusual drowsiness and excess sedation during coadministration of phenothiazines and topiramate due to the risk for additive CNS depression.
    Toremifene: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of toremifene with thioridazine is contraindicated. Thioridazine is associated with a well-established risk of QT prolongation and TdP. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner.
    Tramadol: (Major) Concurrent use of tramadol and thioridazine should be avoided if possible. Antipsychotics may enhance the seizure risk of tramadol. In addition, thioridazine has clinically significant CYP2D6 inhibitory effects and has the potential to decrease the metabolism of CYP2D6 substrates such as tramadol. Although the full pharmacologic impact of increased tramadol exposure is unknown, close monitoring for serious adverse effects, such as seizures, is advisable. In addition, serotonin syndrome may occur during use of tramadol with medications that impair its metabolism. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, hyperreflexia, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Because the analgesic activity of tramadol is due to the activity of both the parent drug and the O-desmethyltramadol metabolite (M1), CYP2D6 inhibition by thioridazine may alter the analgesic response to tramadol. Additive CNS depression may also be seen with the concomitant use of tramadol and thioridazine.
    Tramadol; Acetaminophen: (Major) Concurrent use of tramadol and thioridazine should be avoided if possible. Antipsychotics may enhance the seizure risk of tramadol. In addition, thioridazine has clinically significant CYP2D6 inhibitory effects and has the potential to decrease the metabolism of CYP2D6 substrates such as tramadol. Although the full pharmacologic impact of increased tramadol exposure is unknown, close monitoring for serious adverse effects, such as seizures, is advisable. In addition, serotonin syndrome may occur during use of tramadol with medications that impair its metabolism. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, hyperreflexia, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Because the analgesic activity of tramadol is due to the activity of both the parent drug and the O-desmethyltramadol metabolite (M1), CYP2D6 inhibition by thioridazine may alter the analgesic response to tramadol. Additive CNS depression may also be seen with the concomitant use of tramadol and thioridazine.
    Tranylcypromine: (Moderate) Concurrent use of MAOIs and phenothiazines may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and phenothiazines should be used together cautiously.
    Trazodone: (Contraindicated) Avoid concomitant use of trazodone and thioridazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Tretinoin, ATRA: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Tretinoin; Benzoyl Peroxide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Triazolam: (Major) Limit dosage and duration of benzodiazepines during concomitant phenothiazine use and monitor for unusual drowsiness and sedation due to the risk for additive CNS depression.
    Triclabendazole: (Contraindicated) Avoid concomitant use of triclabendazole and thioridazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Tricyclic antidepressants: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension, including tricyclic antidepressants (TCAs). In addition to additive effects on the cardiovascular system, additive anticholinergic effects and sedation may be observed.
    Trifluoperazine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation and TdP. In addition, coadministration may increase the risk of drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, or seizures.
    Trimethobenzamide: (Moderate) Trimethobenzamide has CNS depressant effects and may cause drowsiness. The concurrent use of trimethobenzamide with other medications that cause CNS depression such as the phenothiazines may potentiate drowsiness or other common side effects of either medication. In addition, the administration of trimethobenzamide to patients who have recently received CNS-depressive drugs has resulted in opisthotonus, seizures, coma, and extrapyramidal symptoms.
    Trimipramine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension, including tricyclic antidepressants (TCAs). In addition to additive effects on the cardiovascular system, additive anticholinergic effects and sedation may be observed.
    Triprolidine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as triprolidine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Triptorelin: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of triptorelin with thioridazine is contraindicated; the efficacy of triptorelin may also be reduced. Thioridazine is associated with a well-established risk of QT prolongation and TdP and is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval. Thioridazine can also cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
    Trospium: (Moderate) Additive anticholinergic effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as trospium.
    Valproic Acid, Divalproex Sodium: (Moderate) The phenothiazines, when used concomitantly with various anticonvulsants, such as valproic acid, can increase CNS depression and also can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either the phenothiazine or the anticonvulsant.
    Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and phenothiazine use. Thiazide diuretics may potentiate the orthostatic hypotension that may occur with phenothiazines.
    Vandetanib: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Thioridazine is considered contraindicated for use along with vandetanib which, when combined with thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Vardenafil: (Contraindicated) Avoid concomitant use of vardenafil and thioridazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Vemurafenib: (Contraindicated) Vemurafenib has been associated with QT prolongation. Because of the potential for torsade de pointes (TdP), use of thioridazine with vemurafenib is contraindicated.
    Venlafaxine: (Contraindicated) Venlafaxine is contraindicated for use with thioridazine. Venlafaxine is associated with a possible risk of QT prolongation. Thioridazine has an established risk of QT prolongation and torsades de pointes (TdP). In addition, venlafaxine impairs the activity of CYP2D6, and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the theoretical risk of prolongation of QTc interval and subsequent arrhythmias due to elevated serum concentrations of thioridazine.
    Verteporfin: (Moderate) Use caution if coadministration of verteporfin with phenothiazines is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like phenothiazines may increase the risk of a photosensitivity reaction.
    Vigabatrin: (Major) Vigabatrin should not be used with phenothiazines, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Vilazodone: (Major) Although the manufacturer of vilazodone states that co-administration of vilazodone (a moderate CYP2D6 inhibitor) with most CYP2D6 substrates is unlikely to result in clinically significant concentration changes, caution is advisable during concurrent use of thioridazine with vilazodone. Thioridazine is a CYP2D6 substrate with an established risk of QT prolongation and torsade de pointes. Elevated concentrations of thioridazine can lead to QT prolongation, ventricular arrhythmias, and sudden death.
    Viloxazine: (Contraindicated) Coadministration of thioridazine and viloxazine is contraindicated due to the potential for increased thioridazine exposure. Increased plasma concentrations of thioridazine are expected to increase the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as torsade de pointes type arrhythmias. Thioridazine is a CYP2D6 substrate and viloxazine is a weak CYP2D6 inhibitor.
    Voclosporin: (Contraindicated) Concomitant use of voclosporin and thioridazine is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Thioridazine is associated with a well-established risk of QT prolongation and TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
    Vonoprazan; Amoxicillin; Clarithromycin: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with clarithromycin which, when combined with a thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Voriconazole: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with voriconazole which, when combined with thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Vorinostat: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Vorinostat therapy is associated with a risk of QT prolongation. Because of the potential for TdP, use of thioridazine with vorinostat is contraindicated.
    Zaleplon: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered with other CNS depressant drugs and they should be used cautiously with anxiolytic, sedative, and hypnotics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of hypnotics and other CNS depressants than with use of a hypnotic alone.
    Ziconotide: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as phenothiazines. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
    Ziprasidone: (Contraindicated) Thioridazine has a well-established risk for QT prolongation and torsade de points (TdP) and is contraindicated for use with other drugs that may prolong the QT interval, including ziprasidone. In addition, coadministration of ziprasidone with phenothiazines may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, seizures, or tardive dyskinesia. The risk of tardive dyskinesia appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Zolpidem: (Moderate) Phenothiazines are CNS depressant drugs that may have cumulative effects when administered with other CNS depressant drugs and they should be used cautiously with anxiolytic, sedative, and hypnotics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of hypnotics and other CNS depressants than with use of a hypnotic alone.
    Zonisamide: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added. Zonisamide may also cause decreased sweating (oligohidrosis), elevated body temperature (hyperthermia), heat intolerance, or heat stroke. The manufacturer recommends caution in using concurrent drug therapies that may predispose patients to heat-related disorders such as antipsychotic phenothiazines. Monitor patients for decreased efficacy of the anticonvulsant, heat intolerance, decreased sweating, or increased body temperature if zonisamide is used with any of these agents.

    PREGNANCY AND LACTATION

    Pregnancy

    Based on recommendations for other phenothiazines, thioridazine use is not recommended in women who are breast-feeding. Phenothiazines are excreted into breast milk; drowsiness, lethargy, and developmental delays have been reported in the nursing infant. The physiology of the infant should be considered when evaluating the risk of exposure to phenothiazines. Phenothiazines may also induce elevated prolactin concentrations and galactorrhea, and thus may interfere with proper lactation. The American Academy of Pediatrics (AAP) classifies chlorpromazine, a related phenothiazine, as a drug for which the effects on a nursing infant are unknown but may be of concern due to drowsiness or lethargy in the infant, a decline in developmental scores, and drug-induced galactorrhea in the mother. Due to individual variability in response to antipsychotics, it may be prudent to continue the existing regimen if ongoing treatment is deemed necessary during breast-feeding; however, alternate medications for consideration include atypical agents such as olanzapine or quetiapine. It should be noted that data regarding the safety of atypical antipsychotics during breast-feeding are limited and chronic administration of any antipsychotic during breast-feeding should be avoided if possible. Regardless of the antipsychotic used, the nursing infant should be closely monitored for excessive drowsiness, lethargy, and developmental delays. Combination treatment with antipsychotics may increase the risk of these adverse events. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Mechanism of Action: Thioridazine blocks postsynaptic dopamine receptors in the mesolimbic system and increases dopamine turnover by blockade of the D2 somatodendritic autoreceptor. After ~12 weeks of chronic therapy, depolarization blockade of dopamine tracts occurs. The decrease in dopamine neurotransmission has been found to correlate to the antipsychotic effects. This D2 blockade is also responsible for the strong extrapyramidal effects observed with this drug. Dopamine blockade in the chemoreceptor trigger zone accounts for the antiemetic effects. Thioridazine possesses strong anticholinergic and alpha-adrenergic receptor blocking effects. Blockade of alpha1-adrenergic receptors produces sedation, muscle relaxation, and cardiovascular effects such as hypotension, reflex tachycardia, and minor changes in ECG patterns.

    PHARMACOKINETICS

    Thioridazine is administered orally. Antipsychotic effects are gradual, with considerable individual patient variation, and maximum effects may not occur for 6 weeks to 6 months. Phenothiazines are distributed widely into body tissues and fluids, and cross the blood-brain barrier. Thioridazine is highly plasma protein-bound (96% to 99%), predominantly to alpha1-acid glycoprotein. Metabolism is extensive, and about 12 metabolites have been identified. There may be some enterohepatic circulation, and two of the metabolites, mesoridazine and sulforidazine, are pharmacologically active. Mesoridazine is twice as potent as thioridazine. The half-life of thioridazine in adults is 21 to 24 hours. There is some conjugation with glucuronides, and these, along with unconjugated metabolites, account for most of the drug found in urine; only a small amount is excreted as unchanged drug. Some excretion may occur via the biliary tract and feces.
     
    Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP2D6, CYP2C19
    Similar to most other phenothiazines, thioridazine is a major substrate of CYP2D6. Thioridazine is a minor substrate of CYP2C19 and a moderate inhibitor of CYP2D6. Due to the risk of QT prolongation and torsade de pointes from elevated plasma concentrations of thioridazine, concomitant use with CYP2D6 inhibitors is contraindicated.

    Oral Route

    Thioridazine is rapidly absorbed following oral administration. The oral bioavailability is 25% to 33%. The time to peak plasma concentrations following an oral dose is 1 to 4 hours.