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Drug Interactions between bexarotene and clozapine

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

cloZAPine bexarotene

Applies to: clozapine and bexarotene

MONITOR CLOSELY: Coadministration of clozapine with other agents that can cause granulocytopenia, neutropenia, or agranulocytosis (severe neutropenia) may increase the risk and/or severity of hematologic toxicity. Clozapine alone is associated with a significant risk of severe neutropenia, defined as an absolute neutrophil count (ANC) of less than 500/µL (0.5 x 10^9/L), and its development appears independent of dose and treatment duration. The exact mechanism by which clozapine leads to neutropenia is unknown; however, several test systems using animal bone marrow cells suggest that clozapine has a suppressant effect on cell division. Some authorities estimate the incidence of neutropenia and severe neutropenia from clozapine therapy at 3% and 0.7%, respectively, with more severe cases occurring during the first 18 to 26 weeks of treatment. Fatal cases of clozapine-induced neutropenia have been rarely reported, and the majority of these cases occurred prior to the recognition of the risk of clozapine-induced neutropenia and the need for routine blood monitoring during clozapine therapy.

MANAGEMENT: If clozapine is used concurrently with an agent known to cause neutropenia (e.g., antineoplastic drugs, some anticonvulsant and antirheumatic medications, albendazole, chloramphenicol, colchicine, dapsone, interferons, linezolid, pentamidine, procainamide, and zidovudine), consider monitoring patients more closely than the standard guidelines suggested in the product labeling. If a patient is receiving concomitant chemotherapy, the treating oncologist should be consulted. Some authorities consider this combination to be contraindicated.

References

  1. (2001) "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals
  2. (2023) "Product Information. CloZAPine (cloZAPine)." Aurobindo Pharma USA Inc
  3. (2023) "Product Information. AA-Clozapine (clozapine)." AA Pharma Inc
  4. (2022) "Product Information. Denzapine (clozapine)." Britannia Pharmaceuticals Ltd
  5. (2022) "Product Information. Clozapine (AKM) (clozapine)." Pharmacor Pty Ltd, 03
View all 5 references

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Drug and food interactions

Moderate

cloZAPine food

Applies to: clozapine

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
View all 4 references

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Moderate

bexarotene food

Applies to: bexarotene

ADJUST DOSING INTERVAL: Food may enhance the oral bioavailability of bexarotene. In one clinical study, bexarotene peak plasma concentration (Cmax) and systemic exposure (AUC) resulting from a 75 to 300 mg dose were 35% and 48% higher, respectively, when administered after a fat-containing meal relative to a glucose solution. In all clinical trials, patients were instructed to take bexarotene with or immediately following a meal.

Coadministration with inhibitors of CYP450 3A4 such as grapefruit juice may theoretically increase the plasma concentrations of bexarotene. In vitro studies suggest that bexarotene is metabolized by CYP450 3A4. However, concomitant administration with multiple doses of ketoconazole, a potent CYP450 3A4 inhibitor, did not alter bexarotene plasma concentrations, which would imply that bexarotene elimination is not substantially dependent on CYP450 3A4 metabolism in vivo.

MANAGEMENT: Because safety and efficacy data are based upon administration with food, bexarotene should be administered once daily with a meal. Patients may want to avoid consuming large amounts of grapefruit or grapefruit juice.

References

  1. (2001) "Product Information. Targretin (bexarotene)." Ligand Pharmaceuticals
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."

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Minor

cloZAPine food

Applies to: clozapine

Caffeine may increase clozapine serum concentrations and exacerbate psychotic symptoms. The mechanism is unknown but may be related to competition for the same metabolic pathway. No specific intervention is necessary; however, if an interaction is suspected it is recommended that caffeine intake be avoided.

References

  1. Carrillo JA, Jerling M, Bertilsson L (1995) "Interaction between caffeine and clozapine - comment." J Clin Psychopharmacol, 15, p. 376-7
  2. Odom-White A, de Leon J (1996) "Clozapine levels and caffeine." J Clin Psychiatry, 57, p. 175-6
  3. Vainer JL, Chouinard G (1994) "Interaction between caffeine and clozapine." J Clin Psychopharmacol, 14, p. 284
  4. Hagg S, Spiset O, Mjorndal T, Dalqvist R (2000) "Effect of caffeine on clozapine pharmacokinetics in healthy volunteers." Br J Clin Pharmacol, 49, p. 59-63
View all 4 references

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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