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Drug Interactions between cholestyramine and Valproate Sodium

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

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Interactions between your drugs

Moderate

valproic acid cholestyramine

Applies to: Valproate Sodium (valproic acid) and cholestyramine

ADJUST DOSING INTERVAL: Cholestyramine may interfere with the gastrointestinal absorption of valproic acid and reduce its bioavailability. In six study subjects, administration of a single 250 mg dose of valproic acid simultaneously with a 4 gram dose of cholestyramine (given twice daily starting one day before valproic acid administration) resulted in an average 15% decrease in valproic acid peak serum concentration and 21% decrease in systemic exposure (AUC) compared to administration alone. By contrast, no significant interaction was observed when valproic acid was given 3 hours before the cholestyramine dose. The bioavailability of valproic acid, relative to administration alone, was 86.2% when given concurrently with cholestyramine and 95.3% when given 3 hours before cholestyramine.

MANAGEMENT: To minimize potential for interaction, valproic acid and cholestyramine should be administered at least 3 hours apart. Patients should be monitored for clinical and laboratory evidence of altered valproate efficacy, and the dosage adjusted if necessary. It is not known whether these precautions are applicable to extended-release valproic acid or divalproex formulations.

References

  1. (2001) "Product Information. Depakene (valproic acid)." Abbott Pharmaceutical
  2. Malloy MJ, Ravis WR, Pennell AT, Diskin CJ (1996) "Effect of cholestyramine resin on single dose valproate pharmacokinetics." Int J Clin Pharmacol Ther, 34, p. 208-11
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."

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Drug and food interactions

Moderate

valproic acid food

Applies to: Valproate Sodium (valproic acid)

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

cholestyramine food

Applies to: cholestyramine

ADJUST DOSING INTERVAL: Bile acid sequestrants and the phosphate binder, sevelamer, can decrease the absorption of fat-soluble vitamins A, D, E, and K. In non-clinical safety studies, rats administered colesevelam at doses greater than 30-fold the projected human clinical dose developed hemorrhage in association with vitamin K deficiency. In a crossover study involving healthy subjects, coadministration of sevelamer with calcitriol resulted in a significant reduction in bioavailability for calcitriol (calcitriol with sevelamer vs calcitriol alone: AUC 137 pg*h/mL vs 318 pg*h/mL and Cmax 40.1 pg/mL vs 49.7 pg/mL, respectively).

MANAGEMENT: Oral vitamin supplements should be administered at least 4 hours before colesevelam and either 1 hour before or 4 to 6 hours after other bile acid sequestrants and sevelamer.

References

  1. (2001) "Product Information. Rocaltrol (calcitriol)." Roche Laboratories
  2. (2001) "Product Information. Welchol (colesevelam)." Daiichi Sankyo, Inc.
  3. (2005) "Product Information. Fosamax Plus D (alendronate-cholecalciferol)." Merck & Co., Inc
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  5. Cerner Multum, Inc. "Australian Product Information."
  6. Peirce D, Hossack S, Poole L, et al. (2011) "The effect of sevelamer carbonate and lanthanum carbonate on the pharmacokinetics of oral calcitriol." Nephrol Dial Transplant, 26, p. 1615-21
View all 6 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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