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Drug Interactions between clozapine and upadacitinib

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

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Interactions between your drugs

Major

cloZAPine upadacitinib

Applies to: clozapine and upadacitinib

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

Major

upadacitinib food

Applies to: upadacitinib

GENERALLY AVOID: Grapefruit, grapefruit juice or supplements containing grapefruit may increase the plasma concentrations of upadacitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in these fruits. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit. In study subjects, administration with the potent CYP450 3A4 inhibitor ketoconazole increased upadacitinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 70% and 75%, respectively. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Upadacitinib side effects including lymphopenia, neutropenia, anemia, serious infections, and hyperlipidemia may be increased.

MONITOR CLOSELY: Smoking during treatment with upadacitinib may increase the risk of major adverse cardiovascular events (MACE) and the risk of developing malignancies. During upadacitinib clinical studies, current or past smokers had an additional increased risk of overall malignancies. Also, upadacitinib may increase patients' risk of MACE, including myocardial infarction, stroke, and cardiovascular death.

MANAGEMENT: The manufacturer advises that concomitant use of upadacitinib with grapefruit, grapefruit juice, or supplements containing grapefruit should be avoided. Caution is advised if upadacitinib is prescribed to current or past smokers. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. The manufacturer recommends discontinuing upadacitinib in patients who have experienced a myocardial infarction or stroke.

References

  1. (2022) "Product Information. Rinvoq (upadacitinib)." AbbVie Pty Ltd, 7
  2. (2022) "Product Information. Rinvoq (upadacitinib)." AbbVie US LLC

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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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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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