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Drug Interactions between Denzapine and divalproex sodium

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

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Interactions between your drugs

Minor

cloZAPine divalproex sodium

Applies to: Denzapine (clozapine) and divalproex sodium

Several reports have suggested that valproate may slightly increase serum clozapine levels and levels of clozapine metabolites. Increased sedation and functional impairment may result. The mechanism of this interaction has not been delineated, but may involve competitive protein binding, which may also result in an increase in valproate concentrations. In contrast, other reports imply that valproate may induce the metabolism of clozapine which would result in a reduction in clozapine plasma levels. If clozapine and valproic acid or any of its derivatives must be used together, close observation for altered clozapine effect is recommended. The clinical significance of this potential interaction is unknown; further investigation is required.

References

  1. Centorrino F, Baldessarini RJ, Kando J, et al. "Serum concentrations of clozapine and its major metabolites - effects of cotreatment with fluoxetine or valproate." Am J Psychiatry 151 (1994): 123-5
  2. Centorrino F, Baldessarini RJ, Kando JC, Frankenburg FR, Volpicelli SA, Flood JG "Clozapine and metabolites - concentrations in serum and clinical findings during treatment of chronically psychotic patients." J Clin Psychopharmacol 14 (1994): 119-25
  3. Cerner Multum, Inc. "Australian Product Information." O 0

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Drug and food interactions

Moderate

cloZAPine food

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

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Moderate

divalproex sodium food

Applies to: divalproex sodium

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

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Minor

cloZAPine food

Applies to: Denzapine (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 "Interaction between caffeine and clozapine - comment." J Clin Psychopharmacol 15 (1995): 376-7
  2. Odom-White A, de Leon J "Clozapine levels and caffeine." J Clin Psychiatry 57 (1996): 175-6
  3. Vainer JL, Chouinard G "Interaction between caffeine and clozapine." J Clin Psychopharmacol 14 (1994): 284
  4. Hagg S, Spiset O, Mjorndal T, Dalqvist R "Effect of caffeine on clozapine pharmacokinetics in healthy volunteers." Br J Clin Pharmacol 49 (2000): 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

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

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