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Drug Interactions between Mysoline and Vanspar

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

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Interactions between your drugs

Major

busPIRone primidone

Applies to: Vanspar (buspirone) and Mysoline (primidone)

MONITOR CLOSELY: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations and pharmacologic effects of buspirone, which is primarily metabolized by the isoenzyme. Conversely, discontinuation of an inducer may increase buspirone plasma concentrations and increase the risk of central nervous system depression and other adverse effects. When a single 30 mg dose of buspirone was administered following treatment with the potent CYP450 3A4 inducer rifampin (600 mg once daily for 5 days) in 10 healthy volunteers, mean buspirone peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by approximately 84% and 90%, respectively, compared to administration following placebo. None of the subjects had a measurable plasma buspirone concentration at 6, 8 or 10 hours after given rifampin, while buspirone concentration could be determined up to 10 hours in all subjects after placebo. Pharmacodynamic effects of buspirone were also significantly reduced by rifampin in the study. Similar results were reported in another pharmacokinetic study conducted by the same group of investigators.

MANAGEMENT: The potential for diminished pharmacologic effects of buspirone should be considered during coadministration with potent CYP450 3A4 inducers. Pharmacologic response to buspirone should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the buspirone dosage adjusted as necessary.

References

  1. "Product Information. Buspar (buspirone)." Bristol-Myers Squibb PROD (2002):
  2. Lamberg TS, Kivisto KT, Neuvonen PJ "Concentrations and effects of buspirone are considerably reduced by rifampicin." Br J Clin Pharmacol 45 (1998): 381-5
  3. Kivisto KT, Lamberg TS, Neuvonen PJ "Interactions of buspirone with itraconazole and rifampicin: Effects on the pharmacokinetics of the active 1-(2-pyrimidinyl)-piperazine metabolite of buspirone." Pharmacol Toxicol 84 (1999): 94-7

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Drug and food interactions

Major

primidone food

Applies to: Mysoline (primidone)

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

References

  1. Gupta RC, Kofoed J "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J 94 (1966): 863-5
  2. Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med 51 (1971): 346-51
  3. Saario I, Linnoila M "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh) 38 (1976): 382-92
  4. Stead AH, Moffat AC "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol 2 (1983): 5-14
  5. Seixas FA "Drug/alcohol interactions: avert potential dangers." Geriatrics 34 (1979): 89-102
View all 5 references

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Moderate

busPIRone food

Applies to: Vanspar (buspirone)

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of buspirone. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: In a small, randomized, crossover study, the consumption of large amounts of grapefruit juice (compared to water) was associated with significantly increased plasma buspirone concentrations, slightly prolonged elimination half-lives, and delayed times to reach peak drug concentration. The perceived pharmacodynamic effect of buspirone, as measured by subjective drowsiness and overall subjective drug effect, was also enhanced by grapefruit juice. These alterations may stem from the delay of gastric emptying as well as inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving buspirone should be advised to avoid consumption of alcohol. Patients also should preferably avoid the consumption of large amounts of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. If this is not possible, the buspirone dose should be taken at least 2 hours before or 8 hours after grapefruit or grapefruit juice. Monitoring for increased CNS depression is recommended.

References

  1. "Product Information. Buspar (buspirone)." Bristol-Myers Squibb PROD (2002):
  2. Lilja JJ, Kivisto KT, Backman JT, Lamberg TS, Neuvonen PJ "Grapefruit juice substantially increases plasma concentrations of buspirone." Clin Pharmacol Ther 64 (1998): 655-60
  3. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77

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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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