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  • CLASSES

    First Generation Antipsychotics
    Phenothiazine Antiemetics

    BOXED WARNING

    Dementia, geriatric, stroke

    Geriatric patients may be more susceptible to the actions and adverse effects of phenothiazines, including tardive dyskinesia, dystonias, orthostatic hypotension, anticholinergic effects, and a risk for falls and fractures. Initiate treatment with lower doses followed by careful dosage titration and close monitoring. Antipsychotics are not FDA-approved for the treatment of dementia-related psychosis in geriatric patients. A boxed warning in the label of all antipsychotics outlines the significantly increased incidence of cerebrovascular events (e.g., stroke, transient ischemic attack), including fatal events, reported in the elderly with dementia-related psychosis receiving antipsychotics compared to placebo. Two population-based, retrospective cohort studies evaluated the risk of death in elderly patients with dementia receiving conventional antipsychotics. One of the studies found that those receiving atypical antipsychotics had an increase in mortality compared to the placebo group and that those receiving conventional antipsychotics had a marginally higher risk of death compared to the atypical antipsychotic group. Investigators from a separate study reported that the risk of death (all-cause mortality) in the conventional antipsychotic group was comparable to and possibly greater than the risk of death in the atypical antipsychotic group. Deaths due to cancer and cardiac disease carried the highest relative risk. According to the Beers Criteria, antipsychotics are considered potentially inappropriate medications (PIMs) in elderly patients, and use should be avoided except for treating schizophrenia or bipolar disorder, and for short-term use as antiemetics during chemotherapy. Avoid use of chlorpromazine in geriatric patients with the following conditions due to the potential for symptom exacerbation or adverse effects: syncope (increased risk of orthostatic hypotension or bradycardia), lower urinary tract symptoms/benign prostatic hyperplasia in men (decreased urinary flow, urinary retention), Parkinson's disease (symptom exacerbation), delirium (possible new-onset or worsening delirium), and dementia (adverse CNS effects). There is an increased risk of stroke and a greater rate of cognitive decline and mortality in persons with dementia receiving antipsychotics, and the Beers expert panel recommends avoiding antipsychotics to treat delirium- or dementia-related behavioral problems unless non-pharmacological options have failed or are not possible and the patient is a substantial threat to self or others. The Beers Panel recommends avoiding antipsychotics in elderly patients with a history of falls or fractures, unless safer alternatives are not available, as antipsychotics can cause ataxia, impaired psychomotor function, syncope, and additional falls. If an antipsychotic must be used, consider reducing the use of other CNS-active medications that increase the risk of falls and fractures and implement strategies to reduce fall risk. Because antipsychotics can cause or exacerbate hyponatremia and SIADH and the elderly are at increased risk of developing these conditions, sodium levels should be closely monitored when starting or changing dosages of antipsychotics in older adults. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). An antipsychotic should generally be used only for the conditions listed in the guidelines (e.g., schizophrenia, mood disorder, Tourette's disorder) and that meet the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for use. There is an increased risk of morbidity and mortality in elderly patients treated with antipsychotics for dementia-related psychosis. Therefore, identify and address all possible causes of behavioral or psychological symptoms of dementia (BPSD) before considering an antipsychotic. To initiate antipsychotic therapy, the patient must be a danger to self or others and 1) symptoms due to mania or psychosis or 2) the plan of care includes documentation of attempted behavioral interventions (except in an emergency). Limit emergency treatment to 7 days or less with evaluation and documentation within 7 days which identifies and addresses contributors/causes. For acute conditions persisting beyond 7 days, non-pharmacologic interventions must be attempted, unless clinically contraindicated, and documented. Treatment of non-acute, chronic, or prolonged BPSD must meet all of the OBRA criteria for BPSD treatment and include monitoring that ensures the behavioral symptoms are not due to a treatable or correctable medical condition, are not due to correctable environmental or treatable psychological stressors alone, and that there is documented evidence of persistence. The LTCF must evaluate the appropriateness of the antipsychotic during or within 2 weeks of admission for a newly admitted resident on an antipsychotic. In all cases, the lowest possible dose and the shortest duration should be prescribed. OBRA provides general dosing guidance for antipsychotic treatment of BPSD. Monitoring of antipsychotics should include evaluation of ongoing effectiveness, the rationale for use, and potential adverse effects (e.g., anticholinergic effects, neurological symptoms, metabolic syndrome, cardiac effects). Antipsychotics are subject to periodic review for effectiveness, necessity, and the potential for gradual dose reduction (GDR) or discontinuation. Refer to the OBRA guidelines for complete information.

    DEA CLASS

    Rx

    DESCRIPTION

    Prototype phenothiazine antipsychotic; potencies of other antipsychotics are compared to oral chlorpromazine 100 mg; also used as a presurgical anxiolytic, antinauseant, and for treatment of intractable hiccups; increased risk of death in elderly patients treated for dementia-related psychosis.

    COMMON BRAND NAMES

    Thorazine

    HOW SUPPLIED

    Chlorpromazine/Chlorpromazine Hydrochloride/Thorazine Intramuscular Inj Sol: 1mL, 25mg
    Chlorpromazine/Chlorpromazine Hydrochloride/Thorazine Oral Tab: 10mg, 25mg, 50mg, 100mg, 200mg

    DOSAGE & INDICATIONS

    For the treatment of schizophrenia.
    Oral dosage (immediate-release formulations)
    Adults

    OUTPATIENTS WITH MILD TO MODERATE SYMPTOMS: Initially, 10 mg PO 3 to 4 times per day or 25 mg PO 2 to 3 times per day. OUTPATIENTS WITH SEVERE SYMPTOMS: Initially, 25 mg PO 3 times per day. After 1 or 2 days, the daily dosage may be increased by 20 to 50 mg at semi-weekly intervals until the patient becomes calm and cooperative. FOR PROMPT CONTROL OF SEVERE SYMPTOMS: The initial treatment should be with intramuscular chlorpromazine; oral administration should be used for subsequent doses in the range of 25 to 50 mg PO 3 times per day. ACUTE SCHIZOPHRENIA IN HOSPITALIZED PATIENTS: Initially, use chlorpromazine intramuscularly until the patient is controlled and cooperative, which generally occurs within 24 to 48 hours. Thereafter, oral doses may be substituted and increased until the patient is calm; total dosage of 500 mg/day is generally sufficient. While gradual increases up to 2,000 mg/day or more may be necessary, the risks generally outweigh the benefits when exceeding 1,000 mg/day for extended periods. When treating psychotic disorders, the dose should be gradually increased until symptoms are controlled. Maximal improvement may not be seen for weeks to months. When the optimal dosage is reached, continue it for 2 weeks then gradually reduce the dosage to the lowest effective maintenance level. A daily dosage of 200 mg is not unusual. Some patients require higher dosages (e.g., 800 mg/day) such as hospitalized patients being discharged. ELDERLY, EMACIATED, OR DEBILITATED ADULTS: In general, dosage levels should be lower. Elderly patients appear to be more susceptible to hypotension and neuromuscular reactions; therefore, close observation is recommended. The dosage should be individualized based on response and tolerability. Dosage should be increased more gradually in elderly patients.

    For the treatment of nausea/vomiting.
    Oral dosage (tablets)
    Adults and Adolescents

    10 to 25 mg PO every 4 to 6 hours as needed. Increase if necessary.

    Children

    0.55 mg/kg PO every 4 to 6 hours as needed.

    Intramuscular dosage
    Adults and Adolescents

    Initially, 25 mg IM. If no hypotension occurs, administer 25 to 50 mg IM every 3 to 4 hours as needed until vomiting stops. Then, switch to oral therapy.

    Adults and Adolescents during surgical procedures

    Initially, 12.5 mg IM. If no hypotension occurs, may repeat once, 30 minutes after the initial dose. The dosage for treating nausea/vomiting during surgical procedures is lower secondary to prolongation and intensification of the effects of anesthetics by chlorpromazine.

    Infants and Children 6 months and older

    The recommended dose is 0.55 mg/kg IM, repeated every 6 to 8 hours as needed. The duration of IM dosage effect may last up to 12 hours in children. Switch to oral therapy as soon as possible. Do not exceed the following maximum IM daily dose limits: Max: If the child is younger than 5 years (less than 22.7 kg), do not exceed 40 mg/day. If child is 5 to 12 years (22.7 to 45.5 kg), do not exceed 75 mg/day.

    Infants and Children 6 months and older during surgical procedures

    Initially, 0.25 mg/kg IM. If no hypotension occurs, may repeat once, 30 minutes after the initial dose. The dosage for treating nausea/vomiting during surgical procedures is lower secondary to prolongation and intensification of the effects of anesthetics by chlorpromazine.

    Intravenous dosage (NOTE: The IV route is for use during surgery only)
    Adults and Adolescents

    Give 2 mg IV after dosage dilution to a concentration of 1 mg/mL with 0.9% Sodium Chloride injection, and administer IV over at least 2 minutes. May repeat at 2 minute intervals as needed. The total dosage administered via fractional IV injections must not exceed 25 mg.

    Infants and Children older than 6 months

    Give 1 mg IV after dosage dilution to 1 mg/mL with 0.9% Sodium Chloride injection, and administer IV over at least 2 minutes (i.e, rate should not exceed 0.5 mg/minute). May repeat at 2 minute intervals as needed. The total dosage administered via fractional IV injections must not exceed 0.25 mg/kg.

    Rectal dosage
    Adults and Adolescents

    NOTE: This drug is discontinued in the U.S. 50 to 100 mg PR every 6 to 8 hours, as needed.

    Infants and Children 6 months and older

    NOTE: This drug is discontinued in the U.S. 1.1 mg/kg PR every 6 to 8 hours, as needed.

    For the adjunctive treatment of tetanus.
    Intramuscular dosage or intermittent intravenous dosage
    Adults and Adolescents

    25 to 50 mg IM or IV every 6 to 8 hours; usually given in conjunction with barbiturates. If the IV route is used, follow manufacturer directions for dosage dilution to 1 mg/mL with 0.9% Sodium Chloride for injection and administer dose via IV infusion at a rate no faster than 1 mg/minute.

    Infants and Children >= 6 months

    0.55 mg/kg IV or IM every 6 to 8 hours. If the IV route is used, follow manufacturer directions for dosage dilution to 1 mg/mL with NS and administer dose via IV infusion at a rate no faster than 0.5 mg/minute. Do not exceed the following maximum daily dose limits: If child weighs less than 22.7 kg, do not exceed 40 mg/day. If child weighs 22.7 to 45.5 kg, do not exceed 75 mg/day, except in severe cases.

    For the treatment of intractable singultus (hiccups).
    Oral dosage
    Adults and Adolescents

    25 to 50 mg PO 3 to 4 times daily. If symptoms persist for 2 to 3 days, parenteral therapy is indicated.

    Intramuscular dosage
    Adults and Adolescents

    If after 2 to 3 days there is no response to oral therapy, a single dose of 25 to 50 mg IM may be administered.

    Continuous IV infusion dosage
    Adults and Adolescents

    If symptoms persist despite IM dosing, a slow IV infusion may be used. The patient should remain flat in bed during the entire infusion, with blood pressure closely monitored. Add 25 to 50 mg of chlorpromazine injection to 500 to 1000 mL of 0.9% Sodium Chloride for injection; administer slowly IV at a rate specified by the prescriber. Do not exceed an IV rate of 1 mg/minute. Discontinue treatment when the infusion is completed.

    For the treatment of acute intermittent porphyria.
    Oral dosage
    Adults and Adolescents

    25 to 50 mg PO 3 to 4 times per day. Treatment usually continues for several weeks; a few patients may require more prolonged treatment.

    Intramuscular dosage
    Adults and Adolescents

    25 mg IM 3 to 4 times per day until the patient can take oral therapy.

    For the treatment of acute psychosis in acutely agitated schizophrenic patients.
    Intramuscular dosage
    Adults

    FOR PROMPT CONTROL OF SEVERE SYMPTOMS: 25 mg IM; may repeat in 1 hour if necessary. Subsequent doses should be oral. ACUTE SCHIZOPHRENIC HOSPITALIZED PATIENTS: 25 mg IM. If needed, give an additional 25 to 50 mg IM in 1 hour. Increase subsequent IM doses gradually over several days, up to 400 mg every 4 to 6 hours in exceptionally severe cases until patient is controlled. Usually the patient becomes quiet and cooperative within 24 to 48 hours and oral doses may be substituted.

    For the treatment of severe behavioral problems associated with oppositional defiant disorder or other disruptive behavioral disorders, or for attention-deficit hyperactivity disorder (ADHD) in pediatric patients who show excessive motor activity with accompanying conduct disorders.
    Oral dosage
    Children

    Initially, 0.55 mg/kg/dose PO every 4 to 6 hours, as needed. Increase gradually every 3 to 4 days as required to control symptoms. If hospitalized, high dosages (i.e., 50 to 100 mg/day or up to 200 mg/day in older children) may be required to treat severe disturbances or psychotic conditions. Dosage must be individualized according to the degree of mental and emotional disturbance exhibited by the patient. In all cases, the lowest effective dosage should be determined for each patient. Continue the titrated effective dose for at least 2 weeks, then gradually reduce the dosage to the lowest effective dose that controls symptoms. NOTE: Behaviors may consist of some or all of the following symptoms (combativeness, impulsivity, attention deficit/hyperactivity, aggression, mood lability, and frustration) which are out of proportion to immediate provocations.

    Intramuscular dosage (for acute, severe agitation in hospitalized pediatric patients)
    Children

    0.55 mg/kg of body weight IM every 6 to 8 hours, as needed. For children younger than 5 years (less than 22.7 kg), total maximum IM dosage is 40 mg/day. For children aged 5 to 12 years (22.7 to 45.5 kg), total maximum IM dosage is 75 mg/day, except in unmanageable cases. Convert to oral therapy as soon as possible. NOTE: Behaviors may consist of some or all of the following symptoms (combativeness, impulsivity, attention deficit/hyperactivity, aggression, mood lability, and frustration) which are out of proportion to immediate provocations.

    For the treatment of acute migraine†.
    Oral dosage
    Adults and Adolescents

    Single doses of 10 to 50 mg PO have been recommended.

    Rectal dosage
    Adults and Adolescents

    NOTE: This drug is discontinued in the US. 25 mg PR. A dosage of 50 to 100 mg PR every 6 to 8 hours has also been recommended.

    Intravenous dosage (for severe cases where oral or rectal preparations cannot be administered)
    Adults and Adolescents

    0.1 mg/kg IV every 15 minutes, up to 3 doses, has been recommended. If the IV route is used, follow manufacturer directions for dosage dilution to 1 mg/mL with 0.9% Sodium Chloride and administer dose via IV infusion at a rate no faster than 1 mg/minute. Keep patient recumbent for the duration of the infusion and for 30 minutes after completion of the dose.

    For the treatment of agitation† or delirium† in hospitalized patients without underlying psychiatric illness.
    Intravenous, Intramuscular, or Oral dosage
    Adults

    Chlorpromazine is not commonly used or recommended in treatment guidelines, due to its pharmacologic profile. A single dose of 25 mg IV, IM, or PO has been recommended for agitated, intensive-care unit patients who require prompt sedation. Repeat doses should be based on clinical response. If the IV route is used, follow manufacturer directions for dosage dilution to 1 mg/mL with 0.9% Sodium Chloride and administer dose via IV infusion at a rate no faster than 1 mg/minute. Keep patient recumbent for the duration of the infusion and for 30 minutes after completion of the dose.

    For the treatment of neonatal abstinence syndrome†.
    NOTE: The use of chlorpromazine in infants under the age of 6 months should be limited to illnesses where the use of the medication could be potentially lifesaving.
    NOTE: Although chlorpromazine is included in current guidelines established by the American Academy of Pediatrics, its use is limited due to occasional adverse effects such as hypothermia, decreased seizure threshold, and eosinophilia.
    Intramuscular or Oral dosage
    Neonates

    0.55 to 0.7 mg/kg IM or PO every 6 hours has been successful in controlling CNS and GI symptoms of neonatal withdrawal syndrome. In one study, chlorpromazine provided adequate sedation and control of irritability and tremors in 250 cases of neonatal heroin withdrawal.

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

    Initially, 10 to 25 mg PO once daily or twice daily. Gradual titration of no more than 10 to 25 mg/day every 4 to 7 days is recommended. Administer daily dosages in 2 to 4 divided doses in order to control symptoms. 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. OBRA Max: 75 mg/day PO in patients meeting the OBRA criteria for treatment, 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

    1000 mg/day PO; up to 2000 mg/day PO for short periods. Debilitated patients require lower total daily dosages.

    Elderly

    1000 mg/day PO. Debilitated patients require lower total daily dosages.

    Adolescents

    1000 mg/day PO; up to 2000 mg/day PO for short periods. Debilitated patients require lower total daily dosages.

    Children

    5—12 years (weight 22.7—45.5 kg): 100—200 mg/day PO or 75 mg/day IM.
    1—4.9 years (weight < 22.7 kg): 50 mg/day PO or 40 mg/day IM.

    Infants

    >= 6 months (weight < 22.7 kg): 50 mg/day PO or 40 mg/day IM.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available. Use with caution, patients with hepatic disease may have decreased drug metabolism. Patients who develop jaundice secondary to chlorpromazine use should have therapy discontinued.

    Renal Impairment

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

    ADMINISTRATION

    Oral Administration

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

    Oral Solid Formulations

    Tablets: May be crushed prior to administration.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Lemon-yellow color does not alter potency. However, markedly discolored solutions should be discarded.

    Intravenous Administration

    NOTE: The intravenous use of chlorpromazine should be limited to the treatment of severe conditions, such as tetanus, severe hiccups, or nausea/vomiting that occurs during surgery.
    Monitoring of blood pressure is recommended.
    Keep patient in a recumbent position for at least 30 minutes following IV administration to minimize hypotensive effects.
     
    Intermittent IV infusion:
    Never inject undiluted chlorpromazine injection into a vein.
    Dilute with unpreserved sodium chloride 0.9% for injection to an approximate final concentration of 1 mg/mL (e.g., 50 mg chlorpromazine diluted with 50 mL 0.9% Sodium Chloride for injection).
    Infuse IV slowly at a rate not to exceed 1 mg/minute in adults and 0.5 mg/minute in children.
     
    Continuous IV infusion:
    Dilute 25 mg to 50 mg in 500 mL to 1000 mL of sodium chloride 0.9% for injection or other compatible large volume IV fluid.
    Protect from light.
    Infuse IV slowly at a rate prescribed by the physician.

    Intramuscular Administration

    Monitoring of blood pressure is recommended during parenteral administration.
    Keep patient in a recumbent position for at least 30 minutes following IV administration to minimize hypotensive effects.
    No dilution necessary. However, if irritation occurs after IM administration, further IM doses may be diluted with 0.9% Sodium Chloride Injection or 2% procaine.
    Inject slowly and deeply into the upper, outer quadrant of buttock.

    Rectal Administration

    Instruct patient on proper use of suppository and avoid excessive handling of the suppository.
    Remove the wrapper and moisten the suppository with water prior to insertion. If suppository is too soft because of storage in a warm place, chill in the refrigerator for 30 minutes or run cold water over it before removing the wrapper.
    Suppository should be retained in rectum for at least 1—3 hour to ensure maximum benefit.

    STORAGE

    Generic:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Thorazine:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Asthma, benzyl alcohol hypersensitivity, phenothiazine hypersensitivity, sulfite hypersensitivity

    Chlorpromazine is contraindicated for use in patients with known hypersensitivity to chlorpromazine or other phenothiazine hypersensitivity. Cross-sensitivity may occur. Injectable preparations of chlorpromazine contain sulfites and should not be used in patients with a known sulfite hypersensitivity. The incidence of sulfite sensitivity and anaphylaxis is more common in patients with asthma than those who are nonasthmatic; chlorpromazine injections should be used cautiously in asthmatic patients. Some injectable formulations of chlorpromazine also contain benzyl alcohol and should not be used in patients with a known benzyl alcohol hypersensitivity.

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

    Chlorpromazine 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 preexisting 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 fever and infection, and appropriate medical intervention should be instituted if necessary. Chlorpromazine should be discontinued in patients with severe neutropenia (ANC < 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

    Chlorpromazine is contraindicated for use in patients in comatose states (i.e., coma), and should be avoided in those with significant CNS depression (e.g., acute head trauma). Phenothiazines have been shown to have deleterious effects on neuronal recovery after acute brain injuries. Brain-injured patients are also more susceptible to adverse CNS effects of the phenothiazines. Chlorpromazine may impair mental and/or physical abilities, therefore, 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

    Chlorpromazine is contraindicated in patients receiving large amounts of CNS depressants (e.g., alcohol, barbiturates, narcotics, etc.). Phenothiazines may prolong and intensify the sedative actions of CNS depressant medications. Chlorpromazine should be used cautiously during dental work, surgery, and other procedures where the use of CNS depressant medications is common. Chlorpromazine dosage reductions are needed when administered during surgical procedures to treat peri-operative emesis. Significant lowering of blood pressure may occur with the use of chlorpromazine during surgical procedures. Chlorpromazine may also suppress the cough reflex significantly, and aspiration of gastric contents/vomitus may occur.

    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 chlorpromazine. 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 preexisting 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 chlorpromazine 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. Periodic evaluation for movement disorders is recommended (e.g., AIMS). Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the initiation of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotics differ in their potential to cause tardive dyskinesia is unknown. 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 even arise after drug discontinuation. The syndrome may remit, partially or completely, if the antipsychotic is withdrawn. Antipsychotics may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown. Given these considerations, chlorpromazine should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that is known to respond to antipsychotics, and for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic therapy, the smallest dose and the shortest duration producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically. If signs and symptoms of tardive dyskinesia appear, chlorpromazine 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

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

    Alcoholism, angina, AV block, bradycardia, bundle-branch block, cardiac arrhythmias, cardiac disease, coronary artery disease, diabetes mellitus, females, heart failure, hypertension, hypokalemia, hypomagnesemia, hypotension, hypovolemia, long QT syndrome, malnutrition, myocardial infarction, orthostatic hypotension, parenteral administration, QT prolongation, tachycardia, thyroid disease, torsade de pointes

    Phenothiazines may potentiate hypotension caused by hypovolemia, the presence of antihypertensive drugs, or a dehydrated state. Hypotension is significant with parenteral administration of chlorpromazine and requires that the patient be recumbent for at least 30 minutes after an IM or IV dose. Hypotension, syncope, angina, tachycardia, and cardiac arrhythmias may be associated with aggressive dose titration. Orthostatic hypotension 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 orthostasis. A fall risk assessment should be completed recurrently in at-risk patients on long-term antipsychotic therapy. If chlorpromazine is administered to patients with cardiac disease, a low initial dosage should be used, followed by gradual dosage titration. Chlorpromazine has an established risk of QT prolongation and torsade de pointes (TdP). Sudden death, thought to occur secondary to cardiac arrest, has also been reported. Chlorpromazine should not be used in individuals with known cardiac conduction defects (e.g., AV block, bundle-branch block, cardiac arrhythmias, family history of congenital QT prolongation syndromes, or previous torsade de pointes). The risk of QT prolongation and TdP is generally higher at elevated concentrations of phenothiazines. However, case reports have included patients receiving therapeutic doses of chlorpromazine. Medications that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use or should be avoided. Use chlorpromazine with caution in patients with cardiac disease or other conditions that may prolong the QT interval including congenital long QT syndrome, heart failure, bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to cause electrolyte imbalances. Females, elderly patients, patients with diabetes mellitus, thyroid disease, malnutrition, alcoholism, or hepatic dysfunction 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. Patients should also report palpitations, irregular heartbeat, or syncope to their prescriber for further evaluation.

    Pulmonary disease

    Chlorpromazine should be used cautiously in patients with significant pulmonary disease. Serious respiratory events have been reported with phenothiazine therapy, including respiratory arrest. If chlorpromazine is administered to patients with severe chronic pulmonary disease, a low initial dosage should be used, followed by gradual dosage titration.

    Encephalopathy, hepatic disease, jaundice

    Phenothiazines, like chlorpromazine, 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, if possible, 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.

    Labor, neonates, obstetric delivery, pregnancy, pregnancy testing

    No well-controlled data are available to determine the safety and efficacy of chlorpromazine 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 major 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 8 infants exposed to chlorpromazine, there were no major malformations reported. 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. Of the 14 women who developed gestational diabetes, 1 was exposed to chlorpromazine. 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

    According to the manufacturer, chlorpromazine is excreted into breast milk, and a decision should be made to discontinue the drug or discontinue nursing, taking into account the importance of the drug to the mother. Reported adverse effects to the nursing infant have included drowsiness or lethargy; the physiology of the young infant should be considered when evaluating the risk of exposure to phenothiazines. Maternal chlorpromazine dosages of <= 200 mg/day PO may be less likely to cause adverse effects in the breast-feeding infant, but more safety data are needed. In addition, phenothiazines may induce hyperprolactinemia and galactorrhea, and thus may interfere with proper lactation. The American Academy of Pediatrics (AAP) classifies chlorpromazine 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. For hyperemesis, prochlorperazine may be considered as an alternative. 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.

    Children, infants, Reye's syndrome

    Chlorpromazine is approved for use in children as young as 6 months for select conditions; chlorpromazine should not be used to treat conditions in children for which specific pediatric dosages have not been established. In general, chlorpromazine should not be used in infants < 6 months of age except in instances where the use of the drug is potentially lifesaving. Chlorpromazine preparations containing benzyl alcohol should be avoided in neonates; exposure to large amounts of benzyl alcohol has been associated with 'gasping syndrome,' a potentially fatal condition characterized by metabolic acidosis and CNS, respiratory, circulatory, and renal dysfunction. Adverse effects, some ranging from mild to those requiring intensive care and prolonged hospitalization, have also been reported after delivery in neonates exposed to antipsychotics during the third trimester. Chlorpromazine liquid oral concentrate contains propylene glycol, therefore, this formulation should be avoided in infants. Children with acute illnesses (e.g., varicella-zoster infections, CNS infections, measles, gastroenteritis, or dehydration) 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 familial QT prolongation. 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 of any age whose signs and symptoms are suggestive of Reye's syndrome.

    Breast cancer, hyperprolactinemia, infertility

    Phenothiazine antipsychotics, like chlorpromazine, 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.

    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 chlorpromazine, 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, anticholinergic effects, and a risk for falls and fractures. Initiate treatment with lower doses followed by careful dosage titration and close monitoring. Antipsychotics are not FDA-approved for the treatment of dementia-related psychosis in geriatric patients. A boxed warning in the label of all antipsychotics outlines the significantly increased incidence of cerebrovascular events (e.g., stroke, transient ischemic attack), including fatal events, reported in the elderly with dementia-related psychosis receiving antipsychotics compared to placebo. Two population-based, retrospective cohort studies evaluated the risk of death in elderly patients with dementia receiving conventional antipsychotics. One of the studies found that those receiving atypical antipsychotics had an increase in mortality compared to the placebo group and that those receiving conventional antipsychotics had a marginally higher risk of death compared to the atypical antipsychotic group. Investigators from a separate study reported that the risk of death (all-cause mortality) in the conventional antipsychotic group was comparable to and possibly greater than the risk of death in the atypical antipsychotic group. Deaths due to cancer and cardiac disease carried the highest relative risk. According to the Beers Criteria, antipsychotics are considered potentially inappropriate medications (PIMs) in elderly patients, and use should be avoided except for treating schizophrenia or bipolar disorder, and for short-term use as antiemetics during chemotherapy. Avoid use of chlorpromazine in geriatric patients with the following conditions due to the potential for symptom exacerbation or adverse effects: syncope (increased risk of orthostatic hypotension or bradycardia), lower urinary tract symptoms/benign prostatic hyperplasia in men (decreased urinary flow, urinary retention), Parkinson's disease (symptom exacerbation), delirium (possible new-onset or worsening delirium), and dementia (adverse CNS effects). There is an increased risk of stroke and a greater rate of cognitive decline and mortality in persons with dementia receiving antipsychotics, and the Beers expert panel recommends avoiding antipsychotics to treat delirium- or dementia-related behavioral problems unless non-pharmacological options have failed or are not possible and the patient is a substantial threat to self or others. The Beers Panel recommends avoiding antipsychotics in elderly patients with a history of falls or fractures, unless safer alternatives are not available, as antipsychotics can cause ataxia, impaired psychomotor function, syncope, and additional falls. If an antipsychotic must be used, consider reducing the use of other CNS-active medications that increase the risk of falls and fractures and implement strategies to reduce fall risk. Because antipsychotics can cause or exacerbate hyponatremia and SIADH and the elderly are at increased risk of developing these conditions, sodium levels should be closely monitored when starting or changing dosages of antipsychotics in older adults. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). An antipsychotic should generally be used only for the conditions listed in the guidelines (e.g., schizophrenia, mood disorder, Tourette's disorder) and that meet the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for use. There is an increased risk of morbidity and mortality in elderly patients treated with antipsychotics for dementia-related psychosis. Therefore, identify and address all possible causes of behavioral or psychological symptoms of dementia (BPSD) before considering an antipsychotic. To initiate antipsychotic therapy, the patient must be a danger to self or others and 1) symptoms due to mania or psychosis or 2) the plan of care includes documentation of attempted behavioral interventions (except in an emergency). Limit emergency treatment to 7 days or less with evaluation and documentation within 7 days which identifies and addresses contributors/causes. For acute conditions persisting beyond 7 days, non-pharmacologic interventions must be attempted, unless clinically contraindicated, and documented. Treatment of non-acute, chronic, or prolonged BPSD must meet all of the OBRA criteria for BPSD treatment and include monitoring that ensures the behavioral symptoms are not due to a treatable or correctable medical condition, are not due to correctable environmental or treatable psychological stressors alone, and that there is documented evidence of persistence. The LTCF must evaluate the appropriateness of the antipsychotic during or within 2 weeks of admission for a newly admitted resident on an antipsychotic. In all cases, the lowest possible dose and the shortest duration should be prescribed. OBRA provides general dosing guidance for antipsychotic treatment of BPSD. Monitoring of antipsychotics should include evaluation of ongoing effectiveness, the rationale for use, and potential adverse effects (e.g., anticholinergic effects, neurological symptoms, metabolic syndrome, cardiac effects). Antipsychotics are subject to periodic review for effectiveness, necessity, and the potential for gradual dose reduction (GDR) or discontinuation. Refer to the OBRA guidelines for complete information.

    Sunlight (UV) exposure

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

    Accidental exposure

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

    Abrupt discontinuation

    Phenothiazines do not cause physical or psychological dependence. However, abrupt discontinuation of chlorpromazine 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 chlorpromazine is withdrawn.

    Renal failure

    Phenothiazines, including chlorpromazine, are not successfully removed by hemodialysis due to their high-protein binding in the serum (>= 90%). Use with caution in patients with renal failure.

    Ocular disease

    Phenothiazines, like chlorpromazine, 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, like chlorpromazine, 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 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/day) may have increased metabolism of the phenothiazines, including chlorpromazine. 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.

    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 chlorpromazine. 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 chlorpromazine 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.

    Radiographic contrast administration

    Phenothiazines 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. Chlorpromazine should not be used for the control of nausea and vomiting associated with these procedures.

    Dysphagia

    Patients with dysphagia or who are at risk for aspiration should be closely monitored while receiving chlorpromazine. 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

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

    Moderate

    akathisia / Delayed / 1.0-10.0
    dystonic reaction / Delayed / 1.0-10.0
    pseudoparkinsonism / Delayed / 1.0-10.0
    constipation / Delayed / 1.0-10.0
    jaundice / Delayed / 1.0-2.0
    psychosis / Early / 0-1.0
    dysphagia / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    cholestasis / Delayed / Incidence not known
    elevated hepatic enzymes / 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
    blurred vision / Early / Incidence not known
    QT prolongation / Rapid / Incidence not known
    hypotension / Rapid / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    orthostatic hypotension / Delayed / Incidence not known
    impotence (erectile dysfunction) / Delayed / Incidence not known
    galactorrhea / Delayed / Incidence not known
    hyperprolactinemia / Delayed / Incidence not known
    ejaculation dysfunction / Delayed / Incidence not known
    priapism / Early / Incidence not known
    urinary retention / Early / Incidence not known
    infertility / Delayed / Incidence not known
    hyponatremia / Delayed / Incidence not known
    hypoglycemia / Early / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    glycosuria / Early / Incidence not known
    peripheral edema / Delayed / Incidence not known
    hyperthermia / Delayed / Incidence not known

    Mild

    dizziness / Early / 1.0-10.0
    photosensitivity / Delayed / 1.0-10.0
    skin hyperpigmentation / Delayed / 0-1.0
    drowsiness / Early / 10.0
    xerostomia / Early / 10.0
    weight gain / Delayed / 10.0
    headache / Early / Incidence not known
    restlessness / Early / Incidence not known
    nausea / Early / Incidence not known
    appetite stimulation / Delayed / Incidence not known
    fever / Early / Incidence not known
    purpura / Delayed / Incidence not known
    mydriasis / Early / Incidence not known
    miosis / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    libido decrease / Delayed / Incidence not known
    menstrual irregularity / Delayed / Incidence not known
    mastalgia / Delayed / Incidence not known
    gynecomastia / Delayed / Incidence not known
    polydipsia / Early / Incidence not known
    nasal congestion / Early / Incidence not known
    hypothermia / Delayed / 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.
    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; Butalbital: (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.
    Acetaminophen; 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.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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.
    Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as chlorpheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur. (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 effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as chlorpheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as chlorpheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur. (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 chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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 effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as doxylamine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    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) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as chlorpheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur. (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: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as diphenhydramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    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 chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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: (Moderate) Concomitant use of oxycodone with phenothiazines may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. Furthermore, oxycodone is metabolized in part by 2D6 to oxymorphone, which represents < 15% of the total administered dose. Concurrent use of some agents that inhibit CYP2D6 (e.g., quinidine) has not been shown to result in clinically significant interactions. However, many phenothiazines are inhibitors of CYP2D6 (e.g., chlorpromazine, perphenazine, thioridazine) and may potentially increase the effects of oxycodone. Also, severe hypotension may be potentiated with concurrent phenothiazine usage or other drug that compromises vasomotor tone.
    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.
    Acetaminophen; Propoxyphene: (Moderate) Phenothiazines can potentiate the CNS depressant action of other drugs such as opiate agonists. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. A dose reduction of one or both drugs may be needed.
    Acetaminophen; Tramadol: (Moderate) Concurrent use of tramadol and chlorpromazine should be avoided if possible. Antipsychotics may enhance the seizure risk of tramadol. In addition, in vitro data suggest that chlorpromazine has 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 chlorpromazine may alter the analgesic response to tramadol. Additive CNS depression may also be seen with the concomitant use of tramadol and chlorpromazine.
    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: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), alfuzosin and chlorpromazine should be used together cautiously. Based on electrophysiology studies performed by the manufacturer, alfuzosin may prolong the QT interval in a dose-dependent manner. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP. Concurrent use may result in additive QT prolongation.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    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: (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 benzodiazepines. 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 other CNS depressants than with sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Aluminum Hydroxide: (Moderate) The absorption of chlorpromazine liquids, suspensions, or concentrates may be decreased by co-administration of antacids. It may be advisable to separate chlorpromazine administration from antacids by 1 to 2 hours. In a small study (n = 6), administration of a magnesium trisilicate and aluminum hydroxide liquid gel antacid with a chlorpromazine liquid suspension resulted in a statistically significant decrease in chlorpromazine concentrations (average 20% decline; approximate range: 6% to 48%). In another kinetic study (n = 10), concurrent use of chlorpromazine liquid concentrate and an aluminum and magnesium hydroxide suspension reduced the urinary excretion of chlorpromazine by 10% to 45%. Adsorption of chlorpromazine to the antacid suspension may have contributed to a subsequent decline in urinary excretion of the drug.
    Aluminum Hydroxide; Magnesium Carbonate: (Moderate) The absorption of chlorpromazine liquids, suspensions, or concentrates may be decreased by co-administration of antacids. It may be advisable to separate chlorpromazine administration from antacids by 1 to 2 hours. In a small study (n = 6), administration of a magnesium trisilicate and aluminum hydroxide liquid gel antacid with a chlorpromazine liquid suspension resulted in a statistically significant decrease in chlorpromazine concentrations (average 20% decline; approximate range: 6% to 48%). In another kinetic study (n = 10), concurrent use of chlorpromazine liquid concentrate and an aluminum and magnesium hydroxide suspension reduced the urinary excretion of chlorpromazine by 10% to 45%. Adsorption of chlorpromazine to the antacid suspension may have contributed to a subsequent decline in urinary excretion of the drug.
    Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) The absorption of chlorpromazine liquids, suspensions, or concentrates may be decreased by co-administration of antacids. It may be advisable to separate chlorpromazine administration from antacids by 1 to 2 hours. In a small study (n = 6), administration of a magnesium trisilicate and aluminum hydroxide liquid gel antacid with a chlorpromazine liquid suspension resulted in a statistically significant decrease in chlorpromazine concentrations (average 20% decline; approximate range: 6% to 48%). In another kinetic study (n = 10), concurrent use of chlorpromazine liquid concentrate and an aluminum and magnesium hydroxide suspension reduced the urinary excretion of chlorpromazine by 10% to 45%. Adsorption of chlorpromazine to the antacid suspension may have contributed to a subsequent decline in urinary excretion of the drug.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) The absorption of chlorpromazine liquids, suspensions, or concentrates may be decreased by co-administration of antacids. It may be advisable to separate chlorpromazine administration from antacids by 1 to 2 hours. In a small study (n = 6), administration of a magnesium trisilicate and aluminum hydroxide liquid gel antacid with a chlorpromazine liquid suspension resulted in a statistically significant decrease in chlorpromazine concentrations (average 20% decline; approximate range: 6% to 48%). In another kinetic study (n = 10), concurrent use of chlorpromazine liquid concentrate and an aluminum and magnesium hydroxide suspension reduced the urinary excretion of chlorpromazine by 10% to 45%. Adsorption of chlorpromazine to the antacid suspension may have contributed to a subsequent decline in urinary excretion of the drug.
    Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) The absorption of chlorpromazine liquids, suspensions, or concentrates may be decreased by co-administration of antacids. It may be advisable to separate chlorpromazine administration from antacids by 1 to 2 hours. In a small study (n = 6), administration of a magnesium trisilicate and aluminum hydroxide liquid gel antacid with a chlorpromazine liquid suspension resulted in a statistically significant decrease in chlorpromazine concentrations (average 20% decline; approximate range: 6% to 48%). In another kinetic study (n = 10), concurrent use of chlorpromazine liquid concentrate and an aluminum and magnesium hydroxide suspension reduced the urinary excretion of chlorpromazine by 10% to 45%. Adsorption of chlorpromazine to the antacid suspension may have contributed to a subsequent decline in urinary excretion of the drug.
    Amantadine: (Moderate) Although the mechanism of amantadine is not clear, it appears it potentiates the actions of dopamine. Since phenothiazines are dopamine antagonists, these drugs should be avoided when possible in patients with Parkinson's disease who require amantadine therapy. Also, the anticholinergic actions of phenothiazines can be additive to those of amantadine, and may increase the risk of antimuscarinic-related side effects. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, neurologic function, and temperature regulation.
    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 symptoms that are associated with ototoxicity induced by the aminoglycosides.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Aminoglycosides: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
    Amiodarone: (Major) Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Amitriptyline: (Moderate) During coadministration of tricyclic antidepressants (TCAs) and chlorpromazine, close monitoring is essential and dose reduction may become necessary to avoid toxicity. Chlorpromazine is associated with an established risk of QT prolongation and torsades de pointes (TdP); case reports have included patients receiving therapeutic doses of chlorpromazine. TCAs may cause cardiac effects (e.g., QT prolongation) in some cases. Additive anticholinergic effects, hypotension, and sedation may also occur.
    Amitriptyline; Chlordiazepoxide: (Moderate) During coadministration of tricyclic antidepressants (TCAs) and chlorpromazine, close monitoring is essential and dose reduction may become necessary to avoid toxicity. Chlorpromazine is associated with an established risk of QT prolongation and torsades de pointes (TdP); case reports have included patients receiving therapeutic doses of chlorpromazine. TCAs may cause cardiac effects (e.g., QT prolongation) in some cases. Additive anticholinergic effects, hypotension, and sedation may also occur. (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 benzodiazepines. 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 other CNS depressants than with sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    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 chlorpromazine. 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 seizure threshold are potential problems with the combined use of amoxapine and chlorpromazine.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Concurrent use of chlorpromazine and clarithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Both clarithromycin and chlorpromazine are specifically associated with an established risk of QT prolongation and TdP.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Concurrent use of chlorpromazine and clarithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Both clarithromycin and chlorpromazine are specifically associated with an established risk of QT prolongation and TdP.
    Amphetamine: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Amphetamine; Dextroamphetamine Salts: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Amphetamine; Dextroamphetamine: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include chlorpromazine.
    Antacids: (Moderate) The absorption of chlorpromazine liquids, suspensions, or concentrates may be decreased by co-administration of antacids. It may be advisable to separate chlorpromazine administration from antacids by 1 to 2 hours. In a small study (n = 6), administration of a magnesium trisilicate and aluminum hydroxide liquid gel antacid with a chlorpromazine liquid suspension resulted in a statistically significant decrease in chlorpromazine concentrations (average 20% decline; approximate range: 6% to 48%). In another kinetic study (n = 10), concurrent use of chlorpromazine liquid concentrate and an aluminum and magnesium hydroxide suspension reduced the urinary excretion of chlorpromazine by 10% to 45%. Adsorption of chlorpromazine to the antacid suspension may have contributed to a subsequent decline in urinary excretion of the drug.
    Anticholinergics: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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.
    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: (Major) Concurrent use of apomorphine and chlorpromazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Limited data indicate that QT prolongation is also possible with apomorphine administration. The change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines; however, large increases (> 60 msecs from pre-dose) have occurred. Doses <= 6 mg SC are associated with minimal increases in QTc; doses > 6 mg SC do not provide additional clinical benefit and are not recommended. In addition, phenothiazines like chlorpromazine are dopamine-receptor antagonists and may antagonize the effects of dopamine agonists, such as apomorphine.
    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: (Major) Concurrent use of chlorpromazine with aripiprazole should be approached with caution and careful monitoring due to a possible risk o f QT prolongation. In addition, chlorpromazine is a CYP2D6 inhibitor. A dosage reduction of aripiprazole may be clinically warranted in patients receiving chlorpromazine and caution is advisable when aripiprazole is given in combination with other antipsychotics. The risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, or seizures may be increased during combined use; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is deemed necessary. 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: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include chlorpromazine. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine.
    Artemether; Lumefantrine: (Major) Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, such as chlorpromazine, coadministration may result in additive QT prolongation. Concomitant use of artemether; lumefantrine with other drugs that prolong the QT interval should be avoided. Consider ECG monitoring if chlorpromazine must be used with or after artemether; lumefantrine treatment. (Major) Artemether; lumefantrine is an inhibitor of and chlorpromazine is metabolized by the CYP2D6 isoenzyme; therefore, coadministration may lead to increased chlorpromazine concentrations. Furthermore, although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Concomitant use of artemether; lumefantrine with drugs that may prolong the QT interval, such as chlorpromazine, should be avoided. Consider ECG monitoring if chlorpromazine must be used with or after artemether; lumefantrine treatment.
    Articaine; Epinephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of phenothiazines. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction.
    Asenapine: (Major) Asenapine has been associated with QT prolongation. According to the manufacturer of asenapine, the drug should be avoided in combination with other agents also known to have this effect. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP) and should be avoided in combination with asenapine. Coadministration of asenapine with phenothiazines, loxapine, thiothixene, molindone, pimozide, haloperidol, or other atypical agents (e.g., aripiprazole, lurasidone, and others) 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.
    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 chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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; Dihydrocodeine: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Phenothiazines can potentiate the CNS depressant action of skeletal muscle relaxants such as orphenadrine. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    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 chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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: (Moderate) Concomitant use of oxycodone with phenothiazines may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. Furthermore, oxycodone is metabolized in part by 2D6 to oxymorphone, which represents < 15% of the total administered dose. Concurrent use of some agents that inhibit CYP2D6 (e.g., quinidine) has not been shown to result in clinically significant interactions. However, many phenothiazines are inhibitors of CYP2D6 (e.g., chlorpromazine, perphenazine, thioridazine) and may potentially increase the effects of oxycodone. Also, severe hypotension may be potentiated with concurrent phenothiazine usage or other drug that compromises vasomotor tone.
    Atazanavir; Cobicistat: (Major) Caution is warranted when cobicistat is administered with chlorpromazine as there is a potential for elevated chlorpromazine and cobicistat concentrations. Chlorpromazine is a CYP2D6 substrate/inhibitor. Cobicistat is a substrate/inhibitor of CYP2D6.
    Atenolol; Chlorthalidone: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Atomoxetine: (Major) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Atomoxetine is considered a drug with a possible risk of torsade de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with atomoxetine include chlorpromazine.
    Atropine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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.
    Atropine; Difenoxin: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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. (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.
    Atropine; Diphenoxylate: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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. (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.
    Atropine; Edrophonium: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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. (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.
    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) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Azithromycin: (Major) Agents that prolong the QT interval, such as azithromycin, could lead to torsade de pointes (TdP) when combined with a phenothiazine, and therefore are generally not recommended for combined use. Phenothiazines have been associated with a risk of QT prolongation and/or TdP. This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Cases of QT prolongation and TdP were also reported during the post-marketing use of azithromycin.
    Baclofen: (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.
    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: (Major) Concurrent use of bedaquiline and chlorpromazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Bedaquiline has been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy. Chlorpromazine, a phenothiazine, is also associated with an established risk of QT prolongation and TdP.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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. (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.
    Belladonna; Opium: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with chlorpromazine 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 effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Bendroflumethiazide; Nadolol: (Moderate) Concomitant treatment with nadolol and phenothiazines, especially in large doses, can have an additive hypotensive effect. (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with chlorpromazine 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.
    Benzodiazepines: (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 benzodiazepines. 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 other CNS depressants than with sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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.
    Benzphetamine: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Benztropine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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.
    Bepridil: (Severe) Patients receiving other drugs which have the potential for QT prolongation, such as phenothiazines, have an increased risk of developing proarrhythmias during bepridil therapy. According to the manufacturer, bepridil is contraindicated for use with drugs that prolong the QT interval due to the risk of TdP.
    Bethanechol: (Moderate) Drugs that possess antimuscarinic properties, such as chlorpromazine, 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: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include chlorpromazine.
    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: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include chlorpromazine. (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) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Bretylium: (Severe) Phenothiazines have been reported to prolong the QT interval and should not be used with other agents also known to have this effect such as bretylium. However, if coadministration is considered necessary by the practitioner, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential.
    Brexpiprazole: (Major) Caution is advisable during concurrent use of brexpiprazole with other antipsychotics such as phenothiazines. The risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, or seizures may be increased during combined use of brexpiprazole and phenothiazines; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is deemed necessary. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the coadministered antipsychotic agent, with low-potency agents (e.g., thioridazine, chlorpromazine) having an increased likelihood of causing sedation, orthostasis, and anticholinergic effects, and high-potency agents (e.g., fluphenazine) having an increased likelihood 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.
    Brimonidine; Timolol: (Moderate) Timolol interacts with phenothiazines by adding to the overall hypotensive effect.
    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 effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as brompheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as brompheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur. (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 effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as brompheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Brompheniramine; Guaifenesin; Hydrocodone: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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 effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as brompheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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 effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as brompheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Brompheniramine; Pseudoephedrine: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as brompheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Buprenorphine: (Major) Due to the potential for QT prolongation and additive CNS depressant effects, cautious use and close monitoring are advisable if concurrent use of chlorpromazine and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Chlorpromazine has a possible risk for QT prolongation and TdP. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If concurrent use of chlorpromazine and buprenorphine is necessary, consider a dose reduction of one or both drugs. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
    Buprenorphine; Naloxone: (Major) Due to the potential for QT prolongation and additive CNS depressant effects, cautious use and close monitoring are advisable if concurrent use of chlorpromazine and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Chlorpromazine has a possible risk for QT prolongation and TdP. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If concurrent use of chlorpromazine and buprenorphine is necessary, consider a dose reduction of one or both drugs. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
    Bupropion: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. In addition, bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Coadministration of bupropion with medications that are metabolized by the CYP2D6 isoenzyme, such as phenothiazines and many other antipsychotics (e.g., haloperidol, risperidone), should be approached with caution. Dosage reductions of these medications may be needed. Conversely, if bupropion therapy is discontinued, the antipsychotic dosage may need to be increased in some patients.
    Bupropion; Naltrexone: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. In addition, bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Coadministration of bupropion with medications that are metabolized by the CYP2D6 isoenzyme, such as phenothiazines and many other antipsychotics (e.g., haloperidol, risperidone), should be approached with caution. Dosage reductions of these medications may be needed. Conversely, if bupropion therapy is discontinued, the antipsychotic dosage may need to be increased in some patients. (Moderate) Patients receiving phenothiazines and naltrexone concomitantly have had symptoms of somnolence and lethargy.
    Buspirone: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as buspirone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    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.
    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: (Major) The prolactin-lowering effect of cabergoline may be antagonized by medications that increase prolactin levels such as phenothiazines. In addition, cabergoline, a dopamine agonist, can diminish the effectiveness of dopamine antagonists such as the phenothiazines.
    Calcium Carbonate; Magnesium Hydroxide: (Moderate) The absorption of chlorpromazine liquids, suspensions, or concentrates may be decreased by co-administration of antacids. It may be advisable to separate chlorpromazine administration from antacids by 1 to 2 hours. In a small study (n = 6), administration of a magnesium trisilicate and aluminum hydroxide liquid gel antacid with a chlorpromazine liquid suspension resulted in a statistically significant decrease in chlorpromazine concentrations (average 20% decline; approximate range: 6% to 48%). In another kinetic study (n = 10), concurrent use of chlorpromazine liquid concentrate and an aluminum and magnesium hydroxide suspension reduced the urinary excretion of chlorpromazine by 10% to 45%. Adsorption of chlorpromazine to the antacid suspension may have contributed to a subsequent decline in urinary excretion of the drug.
    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.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    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 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.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Carbamazepine: (Major) The concomitant use of the phenothiazines and carbamazepine can increase CNS depression and reduce anticonvulsant effectiveness through a lowering of 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. Carbamazepine is a potent inducer of the cytochrome P-450 hepatic oxidase system, and can reduce plasma concentrations of the phenothiazines. If a phenothiazine and carbamazepine must be used together, dosage adjustments of the phenothiazine may be required.
    Carbetapentane; Chlorpheniramine: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as chlorpheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur. (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 effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as chlorpheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur. (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: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as diphenhydramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur. (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) 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) 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) Phenothiazines may inhibit the clinical antiparkinsonian response to levodopa by blocking dopamine receptors in the brain and levodopa may decrease the response to phenothiazines by increasing central dopamine levels. In general, phenothiazines should be avoided in patients requiring therapy for Parkinson's disease unless the benefit of the antipsychotic outweighs the risk of decreased therapeutic response to levodopa or phenothiazines.
    Carbidopa; Levodopa; Entacapone: (Major) Phenothiazines may inhibit the clinical antiparkinsonian response to levodopa by blocking dopamine receptors in the brain and levodopa may decrease the response to phenothiazines by increasing central dopamine levels. In general, phenothiazines should be avoided in patients requiring therapy for Parkinson's disease unless the benefit of the antipsychotic outweighs the risk of decreased therapeutic response to levodopa or phenothiazines.
    Carbinoxamine: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as carbinoxamine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as carbinoxamine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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 effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as carbinoxamine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur. (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; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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 effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as carbinoxamine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Carbinoxamine; Phenylephrine: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as carbinoxamine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur. (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 effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as carbinoxamine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    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 chlorpromazine, may inhibit the hepatic oxidative metabolism of carvedilol.
    Central-acting adrenergic agents: (Moderate) Phenothiazines may produce alpha-adrenergic blockade and appear to have additive hypotensive or CNS effects when administered concurrently with central-acting adrenergic agents.
    Ceritinib: (Major) Avoid coadministration of ceritinib with chlorpromazine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP).
    Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with phenothiazines should generally be avoided. Coadministration may increase the risk of anticholinergic and CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive anticholinergic effects, sedation, and somnolence.
    Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with phenothiazines should generally be avoided. Coadministration may increase the risk of anticholinergic and CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive anticholinergic effects, sedation, and somnolence.
    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.
    Cevimeline: (Moderate) Cevimeline is partially metabolized by CYP2D6. Inhibitors of this isoenzyme, like chlorpromazine, would be expected to lead to an increase in cevimeline plasma concentrations.
    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; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as dexchlorpheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Chlophedianol; 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.
    Chloral Hydrate: (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.
    Chlorcyclizine: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as chlorcyclizine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Chlordiazepoxide: (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 benzodiazepines. 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 other CNS depressants than with sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Chlordiazepoxide; Clidinium: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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. (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 benzodiazepines. 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 other CNS depressants than with sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Chloroquine: (Major) Coadminister chloroquine with other drugs known to prolong the QT interval, such as chlorpromazine, with caution. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); fatalities have been reported. The risk of QT prolongation is increased with higher chloroquine doses. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP.
    Chlorothiazide: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Chlorpheniramine: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as chlorpheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Chlorpheniramine; Codeine: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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 effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as chlorpheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Chlorpheniramine; Dextromethorphan: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as chlorpheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as chlorpheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur. (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; Dihydrocodeine; Phenylephrine: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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 effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as chlorpheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur. (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; Dihydrocodeine; Pseudoephedrine: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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 effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as chlorpheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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 effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as chlorpheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Chlorpheniramine; Hydrocodone: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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 effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as chlorpheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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 effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as chlorpheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur. (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; Pseudoephedrine: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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 effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as chlorpheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Chlorpheniramine; Phenylephrine: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as chlorpheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur. (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 effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as chlorpheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    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) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Chlorthalidone; Clonidine: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    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: (Minor) Cimetidine has been reported to alter the steady-state plasma concentrations of chlorpromazine. It is possible that cimetidine may also reduce the hepatic metabolism of chlorpromazine. Excessive sedation has been reported in a few case reports. There are limited data supporting the clinical significance of this interaction. Another H-2 blocker may be preferred. Monitor the patient for altered clinical response to therapy or excessive sedation if these drugs are co-administered.
    Ciprofloxacin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering chlorpromazine with ciprofloxacin. Phenothiazines have been associated with a risk of QT prolongation and/or TdP. This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Administration of chlorpromazine with ciprofloxacin may cause additive QT prolongation and could lead to TdP, and therefore concurrent use is generally not recommended.
    Cisapride: (Severe) Coadministration of cisapride and chlorpromazine 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. Chlorpromazine is also associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine.
    Citalopram: (Major) Concurrent use of citalopram and chlorpromazine should be avoided. Citalopram causes dose-dependent QT interval prolongation and chlorpromazine is associated with an established risk of QT prolongation and torsade de pointes (TdP). According to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with drugs that are dopamine antagonists such as phenothiazines. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Citalopram is a weak inhibitor of the CYP2D6 pathway and may result in increases in serum phenothiazine concentrations, leading to side effects. Patients receiving a phenothiazine and an SSRI should be monitored for the emergence of serotonin syndrome, neuroleptic malignant syndrome-like reactions, or other adverse effects.
    Clarithromycin: (Major) Concurrent use of chlorpromazine and clarithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Both clarithromycin and chlorpromazine are specifically associated with an established risk of QT prolongation and TdP.
    Clemastine: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as clemastine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    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: (Major) A dosage reduction of CYP2D6 substrates, such as phenothiazines, may be necessary during co-administration of clobazam. Limited in vivo data suggest that clobazam is an inhibitor of CYP2D6. Elevated concentrations of phenothiazines occurring through inhibition of CYP2D6 may increase the risk of adverse effects, including QT prolongation and torsade de pointes. Clobazam, a benzodiazepine, may cause drowsiness or other CNS effects which may be potentiated during concurrent use of conventional antipsychotics including phenothiazines. Antipsychotics may lower the seizure threshold and reduce the effectiveness of clobazam as an anticonvulsant.
    Clofazimine: (Major) Monitor ECGs for QT prolongation when clofazimine is administered with chlorpromazine. QT prolongation and torsade de pointes (TdP) have been reported in patients receiving clofazimine in combination with QT prolonging medications. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP.
    Clomipramine: (Moderate) During coadministration of tricyclic antidepressants (TCAs) and chlorpromazine, close monitoring is essential and dose reduction may become necessary to avoid toxicity. Chlorpromazine is associated with an established risk of QT prolongation and torsades de pointes (TdP); case reports have included patients receiving therapeutic doses of chlorpromazine. TCAs may cause cardiac effects (e.g., QT prolongation) in some cases. Additive anticholinergic effects, hypotension, and sedation may also occur.
    Clonazepam: (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 benzodiazepines. 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 other CNS depressants than with sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Clorazepate: (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 benzodiazepines. 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 other CNS depressants than with sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Clozapine: (Major) Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. The manufacturer of clozapine recommends caution during concurrent use with medications known to cause QT prolongation. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). In addition, coadministration of clozapine with phenothiazines 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.
    Cobicistat: (Major) Caution is warranted when cobicistat is administered with chlorpromazine as there is a potential for elevated chlorpromazine and cobicistat concentrations. Chlorpromazine is a CYP2D6 substrate/inhibitor. Cobicistat is a substrate/inhibitor of CYP2D6.
    Codeine: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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 chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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. (Major) The use of promethazine, a phenothiazine antiemetic, with phenothiazine antipsychotics such as chlorpromazine should be avoided if possible. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). Promethazine has also been associated with QT prolongation. The duplicative actions of the drugs may result in an increased risk for side effects. Coadministration of promethazine and phenothiazine 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 these combinations has not been established and data are very limited, the risk may be increased during combined use versus use of an antipsychotic alone. (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: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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. (Major) The use of promethazine, a phenothiazine antiemetic, with phenothiazine antipsychotics such as chlorpromazine should be avoided if possible. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). Promethazine has also been associated with QT prolongation. The duplicative actions of the drugs may result in an increased risk for side effects. Coadministration of promethazine and phenothiazine 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 these combinations has not been established and data are very limited, the risk may be increased during combined use versus use of an antipsychotic alone.
    COMT inhibitors: (Major) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including phenothiazines, due to the possibility of additive sedation. In addition, phenothiazines may inhibit the clinical antiparkinsonian response by blocking dopamine receptors in the brain.
    Crizotinib: (Major) Avoid coadministration of crizotinib with chlorpromazine due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Chlorpromazine, a phenothiazine, is also associated with an established risk of QT prolongation and torsade de pointes (TdP).
    Cyclobenzaprine: (Moderate) Additive anticholinergic effects may be seen when chlorpromazine is used concomitantly with other drugs with antimuscarinic activity such as cyclobenzaprine. Antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive sedation may also occur.
    Cyproheptadine: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as cyproheptadine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    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.
    Darunavir; Cobicistat: (Major) Caution is warranted when cobicistat is administered with chlorpromazine as there is a potential for elevated chlorpromazine and cobicistat concentrations. Chlorpromazine is a CYP2D6 substrate/inhibitor. Cobicistat is a substrate/inhibitor of CYP2D6.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Caution is warranted when cobicistat is administered with chlorpromazine as there is a potential for elevated chlorpromazine and cobicistat concentrations. Chlorpromazine is a CYP2D6 substrate/inhibitor. Cobicistat is a substrate/inhibitor of CYP2D6.
    Dasatinib: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), dasatinib and chlorpromazine should be used together cautiously. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Caution is advised when coadministered with other drugs that prolong the QT interval. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP.
    Degarelix: (Major) Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use. Drugs with a possible risk for QT prolongation and TdP that should be used with caution with chlorpromazine include degarelix.
    Desflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with chlorpromazine. Halogenated anesthetics can prolong the QT interval. Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use. In addition, phenothiazines can potentiate the CNS-depressant action of anesthetics.
    Desipramine: (Moderate) During coadministration of tricyclic antidepressants (TCAs) and chlorpromazine, close monitoring is essential and dose reduction may become necessary to avoid toxicity. Chlorpromazine is associated with an established risk of QT prolongation and torsades de pointes (TdP); case reports have included patients receiving therapeutic doses of chlorpromazine. TCAs may cause cardiac effects (e.g., QT prolongation) in some cases. Additive anticholinergic effects, hypotension, and sedation may also occur.
    Desmopressin: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with water intoxication, hyponatremia, or SIADH including chlorpromazine. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia.
    Desvenlafaxine: (Major) Dosage adjustments of some phenothiazines may be necessary during concurrent use of desvenlafaxine. Although clinical studies have shown that desvenlafaxine does not have a clinically relevant effect on CYP2D6 inhibition at doses of 100 mg/day, the manufacturer that primary substrates of CYP2D6, such as perphenazine, be dosed at the original level when co-administered with desvenlafaxine 100 mg or lower or when desvenlafaxine is discontinued. The dose of these CYP2D6 substrates should be reduced by up to one-half if co-administered with desvenlafaxine 400 mg/day.
    Deutetrabenazine: (Major) For patients taking a deutetrabenazine dosage more than 24 mg/day with chlorpromazine, assess the QTc interval before and after increasing the dosage of either medication. Clinically relevant QTc prolongation may occur with deutetrabenazine. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and chlorpromazine is a dopamine antagonist. Additionally, concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as chlorpromazine, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Dexchlorpheniramine: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as dexchlorpheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as dexchlorpheniramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    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.
    Dexmethylphenidate: (Moderate) Antipsychotics, such as phenothiazines, and dexmethylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Dexmethylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of dexmethylphenidate.
    Dextroamphetamine: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as diphenhydramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur. (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; Promethazine: (Major) The use of promethazine, a phenothiazine antiemetic, with phenothiazine antipsychotics such as chlorpromazine should be avoided if possible. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). Promethazine has also been associated with QT prolongation. The duplicative actions of the drugs may result in an increased risk for side effects. Coadministration of promethazine and phenothiazine 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 these combinations has not been established and data are very limited, the risk may be increased during combined use versus use of an antipsychotic alone.
    Dextromethorphan; Quinidine: (Severe) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include chlorpromazine.
    Diazepam: (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 benzodiazepines. 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 other CNS depressants than with sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Dicyclomine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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.
    Diethylpropion: (Major) Concurrent use of diethylpropion and phenothiazines may antagonize the anorectic effects of diethylpropion. In addition, diethylpropion can aggravate psychotic states and interfere with the therapeutic effect of phenothiazines.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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.
    Dimenhydrinate: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as dimenhydrinate, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    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: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as diphenhydramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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 effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as diphenhydramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur. (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.
    Diphenhydramine; Ibuprofen: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as diphenhydramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Diphenhydramine; Naproxen: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as diphenhydramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Diphenhydramine; Phenylephrine: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as diphenhydramine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur. (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.
    Disopyramide: (Major) Avoid use of disopyramide with chlorpromazine if possible due to an increased risk for QT prolongation. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP). Phenothiazines have been associated with a risk of QT prolongation and/or TdP. This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Additive anticholinergic effects are also possible, as both drugs exhibit significant anticholinergic activity.
    Dofetilide: (Severe) Phenothiazines have been associated a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Because of the potential for TdP, concurrent use is contraindicated.
    Dolasetron: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), dolasetron and chlorpromazine should be used together cautiously. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP. Concurrent use may further increase the risk for QT prolongation.
    Dolutegravir; Rilpivirine: (Major) Concurrent use of chlorpromazine and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Phenothiazines have also been associated with QT prolongation and/or TdP. This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine.
    Donepezil: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Chlorpromazine has a possible risk for QT prolongation and TdP and should be used cautiously and with close monitoring with donepezil. In addition, conventional antipsychotics with significant anticholinergic effects, such as chlorpromazine, are more likely than other conventional antipsychotics to diminish the therapeutic action of donepezil, and use of an alternative antipsychotic should be considered. Donepezil inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and exerts its therapeutic effect by improving the availability of acetylcholine.
    Donepezil; Memantine: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Chlorpromazine has a possible risk for QT prolongation and TdP and should be used cautiously and with close monitoring with donepezil. In addition, conventional antipsychotics with significant anticholinergic effects, such as chlorpromazine, are more likely than other conventional antipsychotics to diminish the therapeutic action of donepezil, and use of an alternative antipsychotic should be considered. Donepezil inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and exerts its therapeutic effect by improving the availability of acetylcholine.
    Dopamine: (Moderate) The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of phenothiazines.
    Dorzolamide; Timolol: (Moderate) Timolol interacts with phenothiazines by adding to the overall hypotensive effect.
    Doxepin: (Moderate) During coadministration of tricyclic antidepressants (TCAs) and chlorpromazine, close monitoring is essential and dose reduction may become necessary to avoid toxicity. Chlorpromazine is associated with an established risk of QT prolongation and torsades de pointes (TdP); case reports have included patients receiving therapeutic doses of chlorpromazine. TCAs may cause cardiac effects (e.g., QT prolongation) in some cases. Additive anticholinergic effects, hypotension, and sedation may also occur.
    Doxorubicin: (Major) Avoid coadministration of chlorpromazine with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Chlorpromazine 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 effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as doxylamine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Doxylamine; Pyridoxine: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as doxylamine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    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: (Severe) Concomitant use of dronedarone and chlorpromazine is contraindicated. Dronedarone is an inhibitor of CYP2D6. Chlorpromazine is a substrate for CYP2D6. Coadministration of dronedarone and chlorpromazine may result in elevated plasma concentrations of chlorpromazine. In addition, chlorpromazine 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 and is contraindicated.
    Droperidol: (Major) Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). Any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with droperidol include chlorpromazine.
    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: (Moderate) Caution is advisable during concurrent use of chlorpromazine and serotonin norepinephrine reuptake inhibitors (SNRIs) since elevations in plasma concentrations of chlorpromazine may occur. Phenothiazines are CYP2D6 substrates and duloxetine is a CYP2D6 inhibitor. In addition, chlorpromazine is associated with a possible risk of QT prolongation; therefore, cardiac effects are possible.
    Dutasteride; Tamsulosin: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as chlorpromazine. 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: (Major) If possible, avoid coadministration of efavirenz and chlorpromazine, as use of these medications together may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP.
    Efavirenz; Emtricitabine; Tenofovir: (Major) If possible, avoid coadministration of efavirenz and chlorpromazine, as use of these medications together may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) If possible, avoid coadministration of efavirenz and chlorpromazine, as use of these medications together may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP.
    Eliglustat: (Major) Coadministration of chlorpromazine and eliglustat may result in increased concentrations of the phenothiazine and an increased risk of QT prolongation. If coadministration is necessary, use great caution and monitor closely. Consider reducing the dosage of chlorpromazine and titrating to clinical effect. Chlorpromazine is a CYP2D6 substrate associated with an established risk of QT prolongation. Eliglustat is a CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Caution is warranted when cobicistat is administered with chlorpromazine as there is a potential for elevated chlorpromazine and cobicistat concentrations. Chlorpromazine is a CYP2D6 substrate/inhibitor. Cobicistat is a substrate/inhibitor of CYP2D6.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Caution is warranted when cobicistat is administered with chlorpromazine as there is a potential for elevated chlorpromazine and cobicistat concentrations. Chlorpromazine is a CYP2D6 substrate/inhibitor. Cobicistat is a substrate/inhibitor of CYP2D6.
    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; 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: (Major) Concurrent use of chlorpromazine and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Phenothiazines have also been associated with QT prolongation and/or TdP. This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Concurrent use of chlorpromazine and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Phenothiazines have also been associated with QT prolongation and/or TdP. This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Encainide: (Severe) Encainide is significantly metabolized by CYP2D6 isoenzymes. Caution is recommended when administering encainide with CYP2D6 inhibitors, such as chlorpromazine, since encainide exhibits a narrow therapeutic range and large increases in serum concentrations may be associated with severe adverse reactions.
    Encorafenib: (Major) Avoid coadministration of encorafenib and chlorpromazine due to QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP).
    Enflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with chlorpromazine. Halogenated anesthetics can prolong the QT interval. Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use. In addition, phenothiazines can potentiate the CNS-depressant action of anesthetics.
    Enteral Feedings: (Major) Chlorpromazine oral concentrate appears to be physically incompatible with enteral feedings. This would include the dilution of the chlorpromazine concentrate in nutritional enteral supplements such as Ensure or Pediasure. These combinations are best avoided. If the patient is taking enteral feedings, separate the times of administration from the oral concentrate doses. Alternatives for dilution should be used. Chlorpromazine oral concentrate may be diluted with tomato or fruit juice, milk, simple syrup, orange syrup, carbonated beverages, coffee, tea, or water. Semi-solid foods, such as applesauce or pudding, may also be used. This interaction does not occur with other dosage forms, only the chlorpromazine oral concentrate.
    Ephedrine: (Severe) The alpha-adrenergic effects of epinephrine, and possibly of other adrenergic agonists, can be blocked during concurrent administration of phenothiazines. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal,' which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking phenothiazines can have reduced pressor response to ephedrine but this drug is preferred over epinephrine if a vasopressor agent is required.
    Epinephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of phenothiazines. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Eribulin: (Major) Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP ; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use. Drugs with a possible risk for QT prolongation and TdP that should be used with caution with chlorpromazine include eribulin. If coadministration is necessary, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    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: (Major) Concurrent use of chlorpromazine and erythromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Erythromycin is associated with QT prolongation and TdP. Phenothiazines have also been associated with a risk of QT prolongation and/or TdP. This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine.
    Erythromycin; Sulfisoxazole: (Major) Concurrent use of chlorpromazine and erythromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Erythromycin is associated with QT prolongation and TdP. Phenothiazines have also been associated with a risk of QT prolongation and/or TdP. This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine.
    Escitalopram: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as chlorpromazine, should be done with caution and close monitoring. In addition, escitalopram modestly inhibits CYP2D6. This can result in increased concentrations of drugs metabolized via the same pathway, including certain conventional antipsychotic agents (phenothiazines). Decreased metabolism of these CYP2D6 substrates may lead to arrhythmias or other clinically important adverse reactions associated with antipsychotic use such as sedation and extrapyramidal symptoms.
    Esketamine: (Major) Closely monitor patients receiving esketamine and chlorpromazine 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: (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 benzodiazepines. 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 other CNS depressants than with sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    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) Patients should generally be counseled to avoid alcohol use during phenothiazine therapy, due to additive central nervous system (CNS) depression and the potential to increase psychomotor impairment. Phenothiazines may increase, prolong, or intensify the sedative action of other CNS depressants, such as alcohol.
    Ethinyl Estradiol: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Ethinyl Estradiol; Desogestrel: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Ethinyl Estradiol; Etonogestrel: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Ethinyl Estradiol; Levonorgestrel: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate: (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; Norethindrone Acetate; Ferrous fumarate: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Ethinyl Estradiol; Norethindrone: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Ethinyl Estradiol; Norgestimate: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    Ethinyl Estradiol; Norgestrel: (Minor) Oral contraceptives may also cause additive photosensitization with phenothiazines.
    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.
    Ethotoin: (Moderate) Phenothiazines, when used concomitantly with Hydantoins (e.g., phenytoin, ethotoin) 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. In addition to these pharmacodynamic interactions, several individual anticonvulsant agents interact in multiple ways with phenothiazines. Chlorpromazine may interfere with the metabolism of phenytoin and thus precipitate phenytoin toxicity.
    Etomidate: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Ezogabine: (Major) Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use. Drugs with a possible risk for QT prolongation and TdP that should be used with caution with chlorpromazine include ezogabine.
    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.
    Fentanyl: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with chlorpromazine 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: (Major) Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use. Drugs with a possible risk for QT prolongation and TdP that should be used with caution with chlorpromazine include fingolimod. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of torsades de pointes (TdP). Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
    Flavoxate: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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.
    Flecainide: (Major) Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsades de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. In addition, flecainide is significantly metabolized by CYP2D6 isoenzymes. The coadministration of flecainide with drugs that are CYP2D6 inhibitors may result in increased plasma concentrations of flecainide and an increased risk of QT prolongation. Chlorpromazine prolongs the QT interval and is also a CYP2D6 inhibitor and should be used cautiously with flecainide.
    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: (Major) Concurrent use of chlorpromazine and fluconazole should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Fluconazole has been associated with QT prolongation and rare cases of TdP. Phenothiazines have also been associated with a risk of QT prolongation and/or TdP. This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine.
    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: (Major) Fluoxetine is associated with a possible risk of QT prolongation and torsade de pointes (TdP) and chlorpromazine also has an established risk of QT prolongation and TdP. Combination therapy with these agents should be avoided if possible. Fluoxetine is a potent inhibitor of CYP2D6 and may result in increases in serum phenothiazine concentrations, which may lead to phenothiazine-related side effects such as cardiac side effects, hypotension, CNS sedation, or extrapyramidal symptoms. The effects of fluoxetine on hepatic metabolism of interacting drugs may persist for a time after discontinuation of fluoxetine because of its long elimination half-life.
    Fluoxetine; Olanzapine: (Major) Concurrent use of olanzapine and chlorpromazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP. Limited data, including some case reports, suggest that olanzapine may also 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. (Major) Fluoxetine is associated with a possible risk of QT prolongation and torsade de pointes (TdP) and chlorpromazine also has an established risk of QT prolongation and TdP. Combination therapy with these agents should be avoided if possible. Fluoxetine is a potent inhibitor of CYP2D6 and may result in increases in serum phenothiazine concentrations, which may lead to phenothiazine-related side effects such as cardiac side effects, hypotension, CNS sedation, or extrapyramidal symptoms. The effects of fluoxetine on hepatic metabolism of interacting drugs may persist for a time after discontinuation of fluoxetine because of its long elimination half-life.
    Fluphenazine: (Moderate) Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). Fluphenazine, also a phenothiazine, is associated with a possible risk for QT prolongation. Coadministration of chlorpromazine with other phenothiazines may also increase the risk of phenothiazine-related adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures.
    Flurazepam: (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 benzodiazepines. 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 other CNS depressants than with sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Fluvoxamine: (Major) Coadministration may increase the risk of QT prolongation, torsade de pointes (TdP), and elevated chlorpromazine concentrations. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP. QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. In addition, fluvoxamine is a mild inhibitor of CYP2D6, the primary isoenzyme responsible for the metabolism of chlorpromazine. Decreased metabolism of chlorpromazine may lead to clinically important adverse reactions such as QT prolongation or TdP. Serum concentrations of thioridazine, a phenothiazine that is also highly dependent on CYP2D6 for its metabolism, increased three-fold during coadministration with fluvoxamine.
    Food: (Major) It is recommended that patients avoid the use of marijuana, by any route, if they are treated for a psychiatric history, including psychosis and bipolar disorder, as the cannabinoids (the psychoactive ingredients, such as THC) in marijuana can produce psychotoxic effects and may exacerbate psychiatric disorders. A high frequency of use and use of products with high-potency of THC are potential risk factors for psychiatric effects. Additionally, additive CNS effects, such as sedation or CNS depression are possible. Clinical studies suggest that cannabis use may reduce the efficacy of some antipsychotic drugs. In addition, several cannabinoids in marijuana appear to influence the activity of CYP enzymes and P-glycoprotein, which may alter the concentrations of antipsychotics and influence either safety or efficacy, For example, the smoking of marijuana influences the metabolism of some medications in a manner similar to tobacco by inducing CYP1A2.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as chlorpromazine. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Chlorpromazine, a phenothiazine, is also associated with an established risk of QT prolongation and TdP. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Fosphenytoin: (Moderate) Phenothiazines, when used concomitantly with Hydantoins (e.g., phenytoin, ethotoin) 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. In addition to these pharmacodynamic interactions, several individual anticonvulsant agents interact in multiple ways with phenothiazines. Chlorpromazine may interfere with the metabolism of phenytoin and thus precipitate phenytoin toxicity.
    Fospropofol: (Moderate) Fospropofol potentiates respiratory and CNS depression and may enhance the sedative, respiratory depressive, and hypotensive effects of phenothiazines. A reduced dose of fospropofol may be needed for sedation if it is used in conjunction with other medications that cause CNS depression.
    Gabapentin: (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.
    Galantamine: (Moderate) Conventional antipsychotics with significant anticholinergic effects, such as chlorpromazine, are more likely than other conventional antipsychotics to diminish the therapeutic action of galantamine, and 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.
    Gemifloxacin: (Major) Concurrent use of chlorpromazine and gemifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Chlorpromazine is associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. 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. The likelihood of QTc prolongation may increase with increasing dose of gemifloxacin; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
    Gemtuzumab Ozogamicin: (Major) Use gemtuzumab ozogamicin and chlorpromazine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP.
    Gentamicin: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
    Gilteritinib: (Major) Use caution and monitor for evidence of QT prolongation if concurrent use of gilteritinib and chlorpromazine is necessary. Gilteritinib has been associated with QT prolongation. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP).
    Glasdegib: (Major) Avoid coadministration of glasdegib with chlorpromazine due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP).
    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; Pioglitazone: (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.
    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.
    Glycopyrrolate: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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.
    Glycopyrrolate; Formoterol: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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.
    Goserelin: (Major) Avoid coadministration of goserelin with chlorpromazine due to the risk of reduced efficacy of goserelin; QT prolongation may also occur. Chlorpromazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; goserelin is a GnRH analog. Additionally, chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., goserelin) may also prolong the QT/QTc interval.
    Granisetron: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and chlorpromazine should be used together cautiously. Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron with drugs known to prolong the QT interval or are arrhythmogenic, may result in clinical consequences. Phenothiazines have been associated with a risk of QT prolongation or TdP. This risk is generally higher at elevated concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use.
    Guaifenesin; Hydrocodone: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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 chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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.
    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.
    Halofantrine: (Severe) Halofantrine is considered to have a well-established risk for QT prolongation and torsades de pointes. Halofantrine should be avoided in patients receiving drugs which may induce QT prolongation, such as phenothiazines.
    Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with chlorpromazine. Halogenated anesthetics can prolong the QT interval. Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use. In addition, phenothiazines can potentiate the CNS-depressant action of anesthetics.
    Haloperidol: (Major) Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). Other antipsychotics associated with a possible risk for QT prolongation and TdP which should be avoided during treatment with chlorpromazine include haloperidol. 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.
    Halothane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with chlorpromazine. Halogenated anesthetics can prolong the QT interval. Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use. In addition, phenothiazines can potentiate the CNS-depressant action of anesthetics.
    Histrelin: (Major) Avoid coadministration of histrelin with chlorpromazine due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Chlorpromazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Additionally, chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval.
    Homatropine; Hydrocodone: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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 effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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.
    Hydantoins: (Moderate) Phenothiazines, when used concomitantly with Hydantoins (e.g., phenytoin, ethotoin) 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. In addition to these pharmacodynamic interactions, several individual anticonvulsant agents interact in multiple ways with phenothiazines. Chlorpromazine may interfere with the metabolism of phenytoin and thus precipitate phenytoin toxicity.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Hydrochlorothiazide, HCTZ: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Hydrochlorothiazide, HCTZ; Irbesartan: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Hydrochlorothiazide, HCTZ; Lisinopril: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Hydrochlorothiazide, HCTZ; Losartan: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics. (Moderate) Monitor for increased metoprolol adverse reactions including bradycardia and hypotension during coadministration. A dosage reduction for metoprolol may be needed based on response. Concurrent use may increase metoprolol exposure. Metoprolol is a CYP2D6 substrate; phenothiazines are CYP2D6 inhibitors.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Hydrochlorothiazide, HCTZ; Propranolol: (Major) Propranolol appears to inhibit the hepatic metabolism of phenothiazine neuroleptics, and the phenothiazines appear to decrease the hepatic metabolism of propranolol. Chlorpromazine concentrations increase by up to 5-fold in the presence of propranolol. Increased serum concentrations and pharmacologic effects (e.g., CNS, hypotension) may occur. It is not known if other hepatically-metabolized beta-blockers 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) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Hydrochlorothiazide, HCTZ; Quinapril: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Hydrochlorothiazide, HCTZ; Spironolactone: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Hydrochlorothiazide, HCTZ; Telmisartan: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Hydrochlorothiazide, HCTZ; Triamterene: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Hydrocodone: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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 chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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; Phenylephrine: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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.
    Hydrocodone; Potassium Guaiacolsulfonate: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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 chlorpromazine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking chlorpromazine. Limit the use of opioid pain medications with chlorpromazine 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 chlorpromazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with chlorpromazine 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: (Major) Avoid coadministration of hydroxychloroquine and chlorpromazine. Hydroxychloroquine increases the QT interval and should not be administered with other drugs known to prolong the QT interval. Ventricular arrhythmias and torsade de pointes (TdP) have been reported with the use of hydroxychloroquine. Chlorpromazine is associated with an established risk of QT prolongation and TdP.
    Hydroxyzine: (Major) Chlorpromazine should be used cautiously and with close monitoring with hydroxyzine. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP).
    Hyoscyamine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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.
    Ibuprofen; Oxycodone: (Moderate) Concomitant use of oxycodone with phenothiazines may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. Furthermore, oxycodone is metabolized in part by 2D6 to oxymorphone, which represents < 15% of the total administered dose. Concurrent use of some agents that inhibit CYP2D6 (e.g., quinidine) has not been shown to result in clinically significant interactions. However, many phenothiazines are inhibitors of CYP2D6 (e.g., chlorpromazine, perphenazine, thioridazine) and may potentially increase the effects of oxycodone. Also, severe hypotension may be potentiated with concurrent phenothiazine usage or other drug that compromises vasomotor tone.
    Ibutilide: (Major) Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
    Iloperidone: (Major) Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as chlorpromazine. 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.
    Imipramine: (Moderate) During coadministration of tricyclic antidepressants (TCAs) and chlorpromazine, close monitoring is essential and dose reduction may become necessary to avoid toxicity. Chlorpromazine is associated with an established risk of QT prolongation and torsades de pointes (TdP); case reports have included patients receiving therapeutic doses of chlorpromazine. TCAs may cause cardiac effects (e.g., QT prolongation) in some cases. Additive anticholinergic effects, hypotension, and sedation may also occur.
    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.
    Indacaterol; Glycopyrrolate: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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.
    Indapamide: (Moderate) Indapamide may cause electrolyte disturbances, which may increase the potential for proarrhythmic effects of selected phenothiazines.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with chlorpromazine due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP.
    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.
    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.
    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. Therefore ipecac use in the setting of phenothiazine overdose is not recommended.
    Isocarboxazid: (Major) 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: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with chlorpromazine. Halogenated anesthetics can prolong the QT interval. Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use. In addition, phenothiazines can potentiate the CNS-depressant action of 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: (Major) Itraconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with itraconazole include chlorpromazine.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib with chlorpromazine due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Chlorpromazine, a phenothiazine, is associated with an 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 symptoms that are associated with ototoxicity induced by the aminoglycosides.
    Kava Kava, Piper methysticum: (Moderate) Use kava kava with caution when patients are taking phenothiazines like chlorpromazine. Additive sedation and CNS effects are possible. In addition, kava kava has been reported to inhibit many CYP isozymes (i.e., CYP1A2, 2C9, 2C19, 2D6, 3A4, and 4A9/11) and important pharmacokinetic interactions with CNS-active agents that undergo oxidative metabolism via these CYP isozymes are also possible. Chlorpromazine is a primary substrate of CYP2D6 and it is not yet documented if pharmacokinetic interactions occur with kava kava.
    Ketamine: (Moderate) Phenothiazines can potentiate the CNS-depressant action of other drugs such as general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Ketoconazole: (Major) Ketoconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ketoconazole include chlorpromazine.
    Lamotrigine: (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.
    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: (Major) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration of lapatinib with chlorpromazine is necessary; correct electrolyte abnormalities prior to treatment. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP).
    Lenvatinib: (Major) Avoid coadministration of lenvatinib with chlorpromazine due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Chlorpromazine, a phenothiazine, is also associated with an established risk of QT prolongation and torsade de pointes (TdP).
    Leuprolide: (Major) Avoid coadministration of leuprolide with chlorpromazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Chlorpromazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Additionally, chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Leuprolide; Norethindrone: (Major) Avoid coadministration of leuprolide with chlorpromazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Chlorpromazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Additionally, chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Levetiracetam: (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.
    Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with phenothiazines should generally be avoided. Coadministration may increase the risk of anticholinergic and CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive anticholinergic effects, sedation, and somnolence.
    Levodopa: (Major) Phenothiazines may inhibit the clinical antiparkinsonian response to levodopa by blocking dopamine receptors in the brain and levodopa may decrease the response to phenothiazines by increasing central dopamine levels. In general, phenothiazines should be avoided in patients requiring therapy for Parkinson's disease unless the benefit of the antipsychotic outweighs the risk of decreased therapeutic response to levodopa or phenothiazines.
    Levofloxacin: (Major) Concurrent use of chlorpromazine and levofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Additionally, rare cases of TdP have been spontaneously reported during postmarketing surveillance in patients receiving levofloxacin. Phenothiazines have also been associated with a risk of QT prolongation and/or TdP. This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine.
    Levomethadyl: (Severe) Levomethadyl is associated with an established risk of QT prolongation and/or torsades de pointes. Levomethadyl is contraindicated in combination with other agents that may prolong the QT interval, including the phenothiazines.
    Levorphanol: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with chlorpromazine 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.
    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.
    Lisdexamfetamine: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Lithium: (Major) Some atypical antipsychotics are considered first-line adjunctive therapy to mood stabilizers such as lithium. Because both chlorpromazine and lithium have been associated with QT prolongation, coadminister cautiously and with close monitoring. It is also 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: (Major) Monitor the ECG for QT prolongation and monitor for additive orthostatic hypotension and sedation during concurrent use of lofexidine and chlorpromazine. Lofexidine prolongs the QT interval and torsade de pointes (TdP) has been reported during postmarketing use. Chlorpromazine is associated with an established risk of QT prolongation and TdP. Both agents can cause orthostasis and sedation, which may be additive during coadministration.
    Lomefloxacin: (Minor) Phenothiazines may cause additive photosensitization with quinolones. Patients should take care and use proper techniques to limit sunlight and UV exposure.
    Long-acting beta-agonists: (Moderate) Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with chlorpromazine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Loperamide: (Major) At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Drugs with a possible risk for QT prolongation and TdP, like chlorpromazine, should be used cautiously and with close monitoring with loperamide.
    Loperamide; Simethicone: (Major) At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Drugs with a possible risk for QT prolongation and TdP, like chlorpromazine, should be used cautiously and with close monitoring with loperamide.
    Lopinavir; Ritonavir: (Major) Concurrent use of chlorpromazine and lopinavir; ritonavir should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Lopinavir; ritonavir is associated with QT prolongation. Chlorpromazine is also associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine.
    Lorazepam: (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 benzodiazepines. 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 other CNS depressants than with sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Loxapine: (Moderate) Caution is advisable during concurrent use of antipsychotics, including loxapine and chlorpromazine. Coadministration may increase the risk for drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, and seizures.
    Lurasidone: (Major) 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: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as chlorpromazine. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP).
    Magnesium Hydroxide: (Moderate) The absorption of chlorpromazine liquids, suspensions, or concentrates may be decreased by co-administration of antacids. It may be advisable to separate chlorpromazine administration from antacids by 1 to 2 hours. In a small study (n = 6), administration of a magnesium trisilicate and aluminum hydroxide liquid gel antacid with a chlorpromazine liquid suspension resulted in a statistically significant decrease in chlorpromazine concentrations (average 20% decline; approximate range: 6% to 48%). In another kinetic study (n = 10), concurrent use of chlorpromazine liquid concentrate and an aluminum and magnesium hydroxide suspension reduced the urinary excretion of chlorpromazine by 10% to 45%. Adsorption of chlorpromazine to the antacid suspension may have contributed to a subsequent decline in urinary excretion of the drug.
    Magnesium Salts: (Minor) 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.
    Maprotiline: (Major) Phenothiazines have been reported to prolong the QT interval. Because maprotiline is associated with a possible risk for QT prolongation and torsade de pointes (TdP), concurrent use with chlorpromazine should be approached with caution. If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. In addition, additive anticholinergic effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity such as maprotiline. 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 hypotension or CNS effects such as drowsiness may also occur.
    Meclizine: (Moderate) Additive effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity, such as meclizine, a sedating H1-blocker. Phenothiazines, such as thioridazine and chlorpromazine, may exhibit pronounced anticholinergic and sedative effects. 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 CNS effects may also occur.
    Mefloquine: (Major) Concurrent use of chlorpromazine and mefloquine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Chlorpromazine is associated with QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. There is also evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. However, use of mefloquine alone has not been reported to cause QT prolongation.
    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) Melatonin may exhibit pharmacodynamic interactions with the phenothiazines. Melatonin has been co-administered in studies with thioridazine. No clinically significant pharmacokinetic interactions were found. However, melatonin co-administration resulted in increased feelings of cognitive impairment compared to thioridazine alone. Patients may need to be informed of the possibility of additive central nervous system (CNS) effects, such as sedation, dizziness, and CNS impairment.
    Mepenzolate: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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.
    Meperidine: (Major) Additive CNS depression or hypotensive effects are possible during concurrent use of phenothiazines and meperidine. In addition, an increased risk of seizures is possible due to phenothiazine-induced decreases in the seizure threshold, particularly during routine use. If meperidine is used with a phenothiazine, the meperidine dosage is recommended to be reduced by 25% to 50%. Further dose adjustments may be needed.
    Meperidine; Promethazine: (Major) Additive CNS depression or hypotensive effects are possible during concurrent use of phenothiazines and meperidine. In addition, an increased risk of seizures is possible due to phenothiazine-induced decreases in the seizure threshold, particularly during routine use. If meperidine is used with a phenothiazine, the meperidine dosage is recommended to be reduced by 25% to 50%. Further dose adjustments may be needed. (Major) The use of promethazine, a phenothiazine antiemetic, with phenothiazine antipsychotics such as chlorpromazine should be avoided if possible. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). Promethazine has also been associated with QT prolongation. The duplicative actions of the drugs may result in an increased risk for side effects. Coadministration of promethazine and phenothiazine 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 these combinations has not been established and data are very limited, the risk may be increased during combined use versus use of an antipsychotic alone.
    Mephobarbital: (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.
    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 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.
    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; 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. (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: (Major) The need to coadminister methadone with drugs known to prolong the QT interval should be done with extreme caution and a careful assessment of treatment risks versus benefits. Methadone is associated with an increased risk for QT prolongation and torsade de pointes (TdP), especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). In addition, methadone is a substrate for CYP3A4, CYP2D6, and P-glycoprotein (P-gp). Concurrent use of methadone with inhibitors of these enzymes may result in increased serum concentrations of methadone. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP and inhibits CYP2D6. In addition, concomitant use of methadone with another CNS depressant, such as chlorpromazine, can also lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to use of methadone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Methadone should be used with caution and in reduced dosages if used concurrently with a CNS depressant; also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
    Methamphetamine: (Major) Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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.
    Methocarbamol: (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.
    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.
    Methscopolamine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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.
    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) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Methylphenidate: (Moderate) Antipsychotics, such as phenothiazines, and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
    Metoclopramide: (Severe) Metoclopramide is a central dopamine antagonist and may cause extrapyramidal reactions (e.g., acute dystonic reactions, pseudo-parkinsonism, akathisia, tardive dyskinesia), and rarely, neuroleptic malignant syndrome. Metoclopramide is contraindicated with other drugs that are likely to cause extrapyramidal effects since the risk of these effects may be increased. Phenothiazine antiemetics are also central dopamine antagonists and have been associated with extrapyramidal symptoms and rarely, neuroleptic malignant syndrome. In addition, because both phenothiazines and metoclopramide can cause sedation, seizures, or increased prolactin levels, it is possible that the risk of these effects may be increased during concurrent use. The manufacturer of metoclopramide does not specifically contraindicate the use of metoclopramide and phenothiazine antiemetics; however, coadministration should generally be avoided if possible.
    Metolazone: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
    Metoprolol: (Moderate) Monitor for increased metoprolol adverse reactions including bradycardia and hypotension during coadministration. A dosage reduction for metoprolol may be needed based on response. Concurrent use may increase metoprolol exposure. Metoprolol is a CYP2D6 substrate; phenothiazines are CYP2D6 inhibitors.
    Metronidazole: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include chlorpromazine.
    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 chlorpromazine, could theoretically impair mexiletine metabolism; the clinical significance of such interactions is unknown.
    Midazolam: (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 benzodiazepines. 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 other CNS depressants than with sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Midostaurin: (Major) The concomitant use of midostaurin and chlorpromazine may lead to additive QT interval prolongation. If these drugs are used together, consider obtaining electrocardiograms to monitor the QT interval. In clinical trials, QT prolongation was reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). The risk of QT prolongation and TdP is generally higher at elevated concentrations of phenothiazines. However, case reports have included patients receiving therapeutic doses of chlorpromazine.
    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: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpromazine may be increased when co-administered with mirabegron. Chlorpromazine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
    Mirtazapine: (Major) Coadministration may increase the risk of QT prolongation, torsade de pointes, and CNS depression. Due to the possibility of additive effects on the QT interval, caution is advisable during concurrent use of chlorpromazine and mirtazapine. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine. The majority of reports have occurred in the setting of mirtazapine overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation. Both drugs also have CNS depressant properties, and patients should be advised to avoid engaging in activities requiring mental alertness until they are aware of the effects of the combination.
    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.
    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), anticholinergic effects (e.g., constipation, xerostomia), extrapyramidal effects, neuroleptic malignant syndrome, or seizures may occur. 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.
    Monoamine oxidase inhibitors: (Major) 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 chlorpromazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with chlorpromazine 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 chlorpromazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with chlorpromazine 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: (Major) Concurrent use of chlorpromazine and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Moxifloxacin has been associated with prolongation of the QT interval. Additionally, post-marketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded. Phenothiazines have also been associated with a risk of QT prolongation and/or TdP. This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine.
    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 chlorpromazine. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as chlorpromazine, 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 chlorpromazine. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as chlorpromazine, 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: (Major) Avoid the concomitant use of nilotinib and chlorpromazine; significant prolongation of the QT interval may occur. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy. Chlorpromazine is associated with an established risk of QT prolongation and torsade 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.
    Norfloxacin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering chlorpromazine with norfloxacin. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Quinolones have also been associated with a risk of QT prolongation and TdP. For norfloxacin specifically, extremely rare cases of TdP were reported during post-marketing surveillance. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Nortriptyline: (Moderate) During coadministration of tricyclic antidepressants (TCAs) and chlorpromazine, close monitoring is essential and dose reduction may become necessary to avoid toxicity. Chlorpromazine is associated with an established risk of QT prolongation and torsades de pointes (TdP); case reports have included patients receiving therapeutic doses of chlorpromazine. TCAs may cause cardiac effects (e.g., QT prolongation) in some cases. Additive anticholinergic effects, hypotension, and sedation may also occur.
    Octreotide: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), octreotide and chlorpromazine should be used together cautiously. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP. 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 chlorpromazine, may produce additive effects with antidiarrheals if used concomitantly.
    Ofloxacin: (Major) Concurrent use of chlorpromazine and ofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Phenothiazines have been associated with QT prolongation and/or TdP. The risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Some quinolones, including ofloxacin, have also been associated with QT prolongation. Additionally, post-marketing surveillance for ofloxacin has identified very rare cases of TdP.
    Olanzapine: (Major) Concurrent use of olanzapine and chlorpromazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP. Limited data, including some case reports, suggest that olanzapine may also 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.
    Ondansetron: (Major) Monitor ECG for evidence of QT prolongation if coadministration of ondansetron and chlorpromazine is necessary. Ondansetron has been associated with a dose-related increase in the QT interval. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP).
    Oritavancin: (Moderate) Chlorpromazine is metabolized by CYP2D6; oritavancin is a weak CYP2D6 inducer. Plasma concentrations and efficacy of chlorpromazine may be reduced if these drugs are administered concurrently.
    Orphenadrine: (Moderate) Phenothiazines can potentiate the CNS depressant action of skeletal muscle relaxants such as orphenadrine. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Osimertinib: (Major) Avoid coadministration of chlorpromazine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP.
    Oxaliplatin: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and chlorpromazine concomitantly; correct electrolyte abnormalities prior to administration of oxaliplatin. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience.
    Oxazepam: (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 benzodiazepines. 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 other CNS depressants than with sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
    Oxybutynin: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. 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.
    Oxycodone: (Moderate) Concomitant use of oxycodone with phenothiazines may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. Furthermore, oxycodone is metabolized in part by 2D6 to oxymorphone, which represents < 15% of the total administered dose. Concurrent use of some agents that inhibit CYP2D6 (e.g., quinidine) has not been shown to result in clinically significant interactions. However, many phenothiazines are inhibitors of CYP2D6 (e.g., chlorpromazine, perphenazine, thioridazine) and may potentially increase the effects of oxycodone. Also, severe hypotension may be potentiated with concurrent phenothiazine usage or other drug that compromises vasomotor tone.
    Oxymorphone: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with chlorpromazine 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.
    Paliperidone: (Major) Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as chlorpromazine. However, if coadministration is considered necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential. In addition, the risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, or seizures may be increased during combined use of antipsychotics; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is necessary. 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: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include chlorpromazine.
    Paromomycin: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
    Paroxetine: (Major) Substantial increases in concentrations of phenothiazines such as chlorpromazine may occur due to CYP2D6 inhibition by paroxetine, which may increase the risk of adverse effects, including extrapyramidal symptoms. In addition, because chlorpromazine has been associated with QT prolongation and torsade de pointes, concurrent use of a potent CYP2D6 inhibitor such as paroxetine may increase the risk of such events. Lastly, both paroxetine and chlorpromazine may exhibit significant anticholinergic effects that may be additive during concurrent use.
    Pasireotide: (Major) Cautious use of pasireotide and chlorpromazine is needed, as coadministration may have additive effects on the prolongation of the QT interval. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP).
    Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval (e.g. chlorpromazine) is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and chlorpromazine must be continued, closely monitor the patient for QT interval prolongation.
    Peginterferon Alfa-2b: (Moderate) Monitor for adverse effects associated with increased exposure to chlorpromazine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpromazine is a CYP2D6 substrate.
    Pemoline: (Major) Concurrent use of antipsychotics, including phenothiazines, and pemoline should generally be avoided. The drugs may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. The pharmacology of pemoline is poorly understood, but the drug may block central dopamine reuptake,