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Drug Interactions between Norvir and tolvaptan

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

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Interactions between your drugs

Major

ritonavir tolvaptan

Applies to: Norvir (ritonavir) and tolvaptan

CONTRAINDICATED: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of vasopressin receptor antagonists conivaptan and tolvaptan, both of which are almost exclusively metabolized by the isoenzyme. According to the product labeling, administration of oral conivaptan 10 mg in combination with 200 mg of the potent CYP450 3A4 inhibitor ketoconazole resulted in 4- and 11-fold increases in conivaptan peak plasma concentration (Cmax) and systemic exposure (AUC), respectively, compared to administration alone. Similarly, when a single 30 mg oral dose of tolvaptan was administered to 19 healthy volunteers following pretreatment with ketoconazole 200 mg/day for 3 days, tolvaptan Cmax increased by 3.5-fold and AUC increased by 5.4-fold, although 24-hour urine output increased by just 1.3-fold due to the saturable nature of tolvaptan's effect on urinary excretion rate.

MANAGEMENT: Concomitant use of conivaptan or tolvaptan with potent CYP450 3A4 inhibitors is considered contraindicated. Some authorities recommend avoiding concomitant use of conivaptan or tolvaptan during and for 2 weeks after treatment with itraconazole.

References

  1. "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals PROD (2002):
  2. "Product Information. Vaprisol (conivaptan)." Cumberland Pharmaceuticals Inc (2006):
  3. Cerner Multum, Inc. "Australian Product Information." O 0
  4. "Product Information. Samsca (tolvaptan)." Otsuka American Pharmaceuticals Inc (2009):
View all 4 references

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Drug and food interactions

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. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):

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Moderate

tolvaptan food

Applies to: tolvaptan

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of tolvaptan. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. According to the product labeling, administration of tolvaptan with grapefruit juice resulted in a 1.8-fold increase in tolvaptan systemic exposure. The clinical significance is unknown, although increased pharmacologic effects may be expected. Too rapid correction of hyponatremia increases the risk of osmotic demyelination syndrome, which is associated with dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma, and death.

MANAGEMENT: Patients treated with tolvaptan should avoid consumption of grapefruits and grapefruit juice.

References

  1. "Product Information. Samsca (tolvaptan)." Otsuka American Pharmaceuticals Inc (2009):

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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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