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Drug Interactions between clonazepam and Depakote Sprinkles

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

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Interactions between your drugs

Moderate

clonazePAM divalproex sodium

Applies to: clonazepam and Depakote Sprinkles (divalproex sodium)

MONITOR: A single study has suggested that combination therapy with clonazepam and valproic acid may cause severe drowsiness and decreased seizure control. Other studies have not supported this finding. Several case reports have suggested that the combination of clonazepam and valproic acid may precipitate absence status; however, this combination has had beneficial effects in the treatment refractory absence seizures. The mechanism and causality have not been determined. In addition, valproic acid may decrease plasma levels of clonazepam by inducing its hepatic metabolism.

MANAGEMENT: Monitoring for altered efficacy and safety is recommended if valproic acid (or its derivatives) and clonazepam are used together. Alternative therapy may be appropriate if significant side effects or loss of seizure control occur.

References (6)
  1. Watson WA (1979) "Interaction between clonazepam and sodium valproate." N Engl J Med, 300, p. 678-9
  2. Watson B (1979) "Absence status and the concurrent administration of clonazepam and valproate sodium." Am J Hosp Pharm, 36, p. 887
  3. Jeavons PM, Clark JE, Maheshwari MC (1977) "Treatment of generalized epilepsies of childhood and adolescence with sodium valproate("epilim")." Dev Med Child Neurol, 19, p. 9-25
  4. Wilder BJ, Willmore LJ, Bruni J, Villarreal HJ (1978) "Valproic acid: interaction with other anticonvulsant drugs." Neurology, 28, p. 892-6
  5. (2001) "Product Information. Klonopin (clonazepam)." Roche Laboratories
  6. Cerner Multum, Inc. "UK Summary of Product Characteristics."

Drug and food interactions

Moderate

divalproex sodium food

Applies to: Depakote Sprinkles (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 (4)
  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
Moderate

clonazePAM food

Applies to: clonazepam

GENERALLY AVOID: Acute ethanol ingestion may potentiate the CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MANAGEMENT: Patients should be advised to avoid alcohol during benzodiazepine therapy.

References (7)
  1. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM (1977) "Diazepam actions and plasma concentrations following ethanol ingestion." Eur J Clin Pharmacol, 11, p. 345-9
  2. Whiting B, Lawrence JR, Skellern GG, Meier J (1979) "Effect of acute alcohol intoxication on the metabolism and plasma kinetics of chlordiazepoxide." Br J Clin Pharmacol, 7, p. 95-100
  3. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI (1981) "Benzodiazepine overdosage: plasma concentrations and clinical outcome." Psychopharmacology (Berl), 73, p. 381-3
  4. Juhl RP, Van Thiel DH, Dittert LW, Smith RB (1984) "Alprazolam pharmacokinetics in alcoholic liver disease." J Clin Pharmacol, 24, p. 113-9
  5. Ochs HR, Greenblatt DJ, Arendt RM, Hubbel W, Shader RI (1984) "Pharmacokinetic noninteraction of triazolam and ethanol." J Clin Psychopharmacol, 4, p. 106-7
  6. Staak M, Raff G, Nusser W (1979) "Pharmacopsychological investigations concerning the combined effects of dipotassium clorazepate and ethanol." Int J Clin Pharmacol Biopharm, 17, p. 205-12
  7. Nichols JM, Martin F, Kirkby KC (1993) "A comparison of the effect of lorazepam on memory in heavy and low social drinkers." Psychopharmacology (Berl), 112, p. 475-82

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

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