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Drug Interactions between Clozaril and esomeprazole

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

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Interactions between your drugs

Moderate

cloZAPine esomeprazole

Applies to: Clozaril (clozapine) and esomeprazole

MONITOR: Coadministration with omeprazole may decrease the plasma concentrations of clozapine. The proposed mechanism is omeprazole induction of clozapine metabolism via CYP450 1A2. Two case reports describe patients stabilized on clozapine who experienced a 42% and 45% decrease in their plasma clozapine levels following the addition of omeprazole. No changes in their clinical presentation were noted, however. In a retrospective study of the medical files of 13 psychiatric patients receiving both clozapine and omeprazole, a switch to pantoprazole was associated with a significant rise of the serum clozapine levels in all nonsmokers relative to smokers, although the daily dosage of clozapine was unchanged. Presumably, the increase was due to the discontinuation of CYP450 1A2 induction by omeprazole in nonsmokers, whereas the isoenzyme remained induced in patients who smoked, as cigarette smoke is a known inducer of CYP450 1A2. Theoretically, this interaction could also occur with esomeprazole, the S-enantiomer of omeprazole.

MANAGEMENT: Pharmacologic response and serum clozapine levels should be monitored more closely whenever omeprazole or esomeprazole is added to or withdrawn from therapy, and the clozapine dosage adjusted as necessary. Alternatively, use of another proton pump inhibitor such as pantoprazole may be considered.

References

  1. Frick A, Kopitz J, Bergemann N (2003) "Omeprazole reduces clozapine plasma concentrations. A case report." Pharmacopsychiatry, 36, p. 121-3
  2. Mookhoek EJ, Loonen AJ (2004) "Retrospective evaluation of the effect of omeprazole on clozapine metabolism." Pharm World Sci, 26, p. 180-2

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Drug and food interactions

Moderate

cloZAPine food

Applies to: Clozaril (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

esomeprazole food

Applies to: esomeprazole

ADJUST DOSING INTERVAL: Food may interfere with the absorption of esomeprazole. The manufacturer reports that the area under the concentration-time curve for esomeprazole following a single 40 mg dose was 33% to 53% lower when administered after food intake as opposed to during fasting conditions.

MANAGEMENT: Esomeprazole should be taken at least one hour before meals. When administered to patients receiving continuous enteral nutrition, some experts recommend that the tube feeding should be interrupted for at least 1 hour before and 1 hour after the dose of esomeprazole is given.

References

  1. (2001) "Product Information. Nexium (esomeprazole)." Astra-Zeneca Pharmaceuticals
  2. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT (2009) "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm, 66, p. 1438-67

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Minor

cloZAPine food

Applies to: Clozaril (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.

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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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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