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Drug Interaction Report

3 potential interactions and/or warnings found for the following 2 drugs:

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Interactions between your drugs

Major

indinavir flibanserin

Applies to: indinavir, flibanserin

CONTRAINDICATED: Coadministration with moderate and potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of flibanserin, which is primarily metabolized by CYP450 3A4 and, to a lesser extent, by CYP450 2C19. High plasma levels of flibanserin may increase the risk of severe hypotension, syncope, and central nervous system depression. In 15 healthy female subjects, administration of a single 100 mg dose of flibanserin following pretreatment with fluconazole (400 mg once, then 200 mg once daily for 5 days), a moderate CYP450 3A4 and potent CYP450 2C19 inhibitor, increased flibanserin peak plasma concentration (Cmax) and systemic exposure (AUC) by 2.2- and 7-fold, respectively, compared to administration of flibanserin alone. Hypotension or syncope requiring therapeutic intervention (placement in supine position with legs elevated) occurred in 3 (20%) subjects given flibanserin and fluconazole, compared to no subject given flibanserin alone or fluconazole alone. One of the 3 subjects became unresponsive with a blood pressure of 64/41 mmHg and was taken to the hospital emergency department, where she required intravenous saline. In another study, flibanserin Cmax increased by 1.8-fold and AUC increased by 4.5-fold when a single 50 mg dose was administered to 24 healthy female subjects following pretreatment with ketoconazole (400 mg once daily for 5 days), a potent CYP450 3A4 inhibitor. Syncope occurred in 1 (4%) of 24 subjects receiving flibanserin and ketoconazole, 1 (4%) of 24 subjects receiving flibanserin alone, and no subject receiving ketoconazole alone. Likewise, when a single 50 mg dose of flibanserin was given to 12 healthy male and female subjects following pretreatment with itraconazole (400 mg once, then 200 mg once daily for 4 days), flibanserin Cmax and AUC increased by 1.7- and 2.6-fold, respectively. It should be noted that the 200 mg itraconazole dose does not maximally inhibit CYP450 3A4.

MANAGEMENT: Concomitant use of flibanserin with moderate or potent CYP450 3A4 inhibitors is considered contraindicated. When initiating flibanserin following treatment with a moderate or potent CYP450 3A4 inhibitor, the manufacturer recommends waiting until 2 weeks after the last dose of CYP450 3A4 inhibitor. Conversely, if a moderate or potent CYP450 3A4 inhibitor is required during flibanserin therapy, flibanserin should be discontinued at least 2 days before starting the CYP450 3A4 inhibitor. Close monitoring for signs of hypotension and syncope is advised if the CYP450 3A4 inhibitor is needed sooner.

References

  1. (2015) "Product Information. Addyi (flibanserin)." Sprout Pharmaceuticals

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Drug and food interactions

Major

flibanserin food

Applies to: flibanserin

CONTRAINDICATED: Grapefruit juice may increase the plasma concentrations of flibanserin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In 26 healthy female subjects, administration of a single 100 mg dose of flibanserin with 240 mL grapefruit juice increased flibanserin peak plasma concentration (Cmax) and systemic exposure (AUC) by 1.1- and 1.4-fold, respectively, compared to administration of flibanserin alone. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

ADJUST DOSING INTERVAL: Coadministration of flibanserin with alcohol may potentiate the risk of severe hypotension, syncope, and central nervous system depression. In a dedicated alcohol interaction study, hypotension or syncope requiring therapeutic intervention (ammonia salts and/or placement in supine or Trendelenberg position) occurred in 4 (17%) of 23 subjects given flibanserin 100 mg with 0.4 g/kg alcohol (equivalent to two 12 ounce cans of beer containing 5% alcohol content, two 5 ounce glasses of wine containing 12% alcohol content, or two 1.5 ounce shots of 80-proof spirit in a 70 kg person) consumed over 10 minutes in the morning. In these four subjects, systolic blood pressure reductions ranged from 28 to 54 mmHg and diastolic blood pressure reductions ranged from 24 to 46 mmHg. In addition, 6 (25%) of 24 subjects coadministered flibanserin with 0.8 g/kg alcohol experienced orthostatic hypotension when standing from a sitting position. Systolic and diastolic blood pressure reductions in these 6 subjects ranged from 22 to 48 mmHg and 0 to 27 mmHg, respectively, with one requiring therapeutic intervention. No adverse events requiring therapeutic intervention were observed when flibanserin or alcohol was administered alone. Somnolence was reported in 67%, 74%, and 92% of subjects who received flibanserin alone, flibanserin with 0.4 g/kg ethanol, and flibanserin with 0.8 g/kg ethanol, respectively. Subsequent data from postmarketing trials showed that the risk of severe hypotension and syncope was reduced when women who consumed up to two alcoholic drinks waited at least two hours before taking flibanserin.

MANAGEMENT: Concomitant use of flibanserin with moderate or potent CYP450 3A4 inhibitors such as grapefruit juice is considered contraindicated. The patient should be advised to avoid the consumption of grapefruit and grapefruit juice during treatment, and to take flibanserin at bedtime to minimize the risk of hypotension, syncope, accidental injury, and central nervous system depression. In addition, patients should consume no more than 1 to 2 alcoholic drinks and discontinue drinking alcohol at least two hours before taking flibanserin at bedtime; otherwise, they should skip the flibanserin dose that evening. Alcohol should not be consumed until at least the morning after taking flibanserin at bedtime. A standard alcoholic drink contains 14 g of pure alcohol and is equivalent to one 12-ounce regular beer (5% alcohol), 5-ounces wine (12% alcohol), or 1.5 ounces of distilled spirits/shot (40% alcohol).

References

  1. (2015) "Product Information. Addyi (flibanserin)." Sprout Pharmaceuticals

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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

  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

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Therapeutic duplication warnings

No duplication 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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Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.