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Drug Interactions between indinavir and tolvaptan

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

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Interactions between your drugs

Major

indinavir tolvaptan

Applies to: indinavir 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 (4)
  1. (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  2. (2006) "Product Information. Vaprisol (conivaptan)." Cumberland Pharmaceuticals Inc
  3. Cerner Multum, Inc. "Australian Product Information."
  4. (2009) "Product Information. Samsca (tolvaptan)." Otsuka American Pharmaceuticals Inc

Drug and food interactions

Moderate

indinavir food

Applies to: indinavir

ADJUST DOSING INTERVAL: According to the manufacturer, coadministration with a meal high in calories, fat, and protein reduces the absorption of indinavir. In ten patients given indinavir in this manner, the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of indinavir decreased by an average of 84% and 77%, respectively. In contrast, grapefruit juice may have only minor effects on the oral bioavailability of indinavir. The manufacturer's package labeling states that administration of a single 400 mg dose of indinavir with 8 oz. of grapefruit juice decreased indinavir AUC by an average of 26%. Likewise, a study consisting of 14 HIV-infected subjects found no uniform nor significant changes in steady-state indinavir AUC during administration with double-strength grapefruit juice compared to water. There was, however, a delay in absorption (Tmax) due to grapefruit juice that is unlikely to be of clinical significance.

MANAGEMENT: To ensure maximal oral absorption, indinavir should be administered without food but with water 1 hour before or 2 hours after a meal. Alternatively, indinavir may be administered with other liquids such as skim milk, juice, coffee, or tea, or with a light meal (e.g., dry toast with jelly, juice, and coffee with skim milk and sugar; corn flakes, skim milk and sugar).

References (3)
  1. (2001) "Product Information. Crixivan (indinavir)." Merck & Co., Inc
  2. Yeh KC, Deutsch PJ, Haddix H, Hesney M, Hoagland V, Ju WD, Justice SJ, Osborne B, Sterrett AT, Stone JA, Woolf E, Waldman S (1998) "Single-dose pharmacokinetics of indinavir and the effect of food." Antimicrob Agents Chemother, 42, p. 332-8
  3. Shelton MJ, Wynn HE, Newitt RG, DiFrancesco R (2001) "Effects of grapefruit juice on pharmacokinetic exposure to indinavir in HIV-positive subjects." J Clin Pharmacol, 41, p. 435-42
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)
  1. (2009) "Product Information. Samsca (tolvaptan)." Otsuka American Pharmaceuticals Inc

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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