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Drug Interactions between Norvir and Vanspar

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

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Interactions between your drugs

Moderate

busPIRone ritonavir

Applies to: Vanspar (buspirone) and Norvir (ritonavir)

MONITOR: In one case report, the combination of ritonavir and buspirone was associated with development of Parkinson-like symptoms including ataxia, shuffling gait, cogwheel rigidity, resting tremor, and sad affect with masked features. The proposed mechanism of interaction is ritonavir inhibition of buspirone metabolism via CYP450 3A4, resulting in supratherapeutic levels of buspirone. The patient, an HIV-positive man, had been receiving buspirone 40 mg every morning and 30 mg every evening for 2 years prior to the introduction of ritonavir/indinavir combination therapy (400 mg/400 mg twice daily). The symptoms began 6 weeks after start of the combination and completely resolved 2 weeks after a reduction of buspirone dosage to 15 mg three times a day and substitution of ritonavir/indinavir with amprenavir (1200 mg twice daily). The patient continued to receive buspirone for an additional 12 months without further incident.

MANAGEMENT: Caution is recommended if buspirone is administered with ritonavir. Pharmacologic response to buspirone should be monitored more closely whenever ritonavir is added to or withdrawn from therapy, and the buspirone dosage adjusted as necessary. Patients should be advised to notify their physician if they experience Parkinson-like or other extrapyramidal symptoms.

References

  1. Clay PG, Adams MM (2003) "Pseudo-Parkinson disease secondary to ritonavir-buspirone interaction." Ann Pharmacother, 37, p. 202-5

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Drug and food interactions

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

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Moderate

ritonavir food

Applies to: Norvir (ritonavir)

ADJUST DOSING INTERVAL: Administration with food may modestly affect the bioavailability of ritonavir from the various available formulations. When the oral solution was given under nonfasting conditions, peak ritonavir concentrations decreased 23% and the extent of absorption decreased 7% relative to fasting conditions. Dilution of the oral solution (within one hour of dosing) with 240 mL of chocolate milk or a nutritional supplement (Advera or Ensure) did not significantly affect the extent and rate of ritonavir absorption. When a single 100 mg dose of the tablet was administered with a high-fat meal (907 kcal; 52% fat, 15% protein, 33% carbohydrates), approximately 20% decreases in mean peak concentration (Cmax) and systemic exposure (AUC) were observed relative to administration after fasting. Similar decreases in Cmax and AUC were reported when the tablet was administered with a moderate-fat meal. In contrast, the extent of absorption of ritonavir from the soft gelatin capsule formulation was 13% higher when administered with a meal (615 KCal; 14.5% fat, 9% protein, and 76% carbohydrate) relative to fasting.

MANAGEMENT: Ritonavir should be taken with meals to enhance gastrointestinal tolerability.

References

  1. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical

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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.

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