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Drug Interactions between Desyrel and indinavir

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

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Interactions between your drugs

Moderate

traZODone indinavir

Applies to: Desyrel (trazodone) and indinavir

ADJUST DOSE: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations and pharmacologic effects of trazodone, which is primarily metabolized by the isoenzyme. In ten healthy volunteers, administration of a single 50 mg dose of trazodone in combination with the potent CYP450 3A4 inhibitor ritonavir (200 mg orally for 4 doses) increased mean trazodone peak plasma concentration (Cmax) by 34% and systemic exposure (AUC) by 137% compared to administration with placebo. Trazodone elimination half-life was prolonged 122% by ritonavir, while apparent oral clearance decreased 52%. Sedation, fatigue, and performance impairment were also increased during coadministration with ritonavir, and three subjects experienced nausea, dizziness, and hypotension. Although not reported in the study, the potential for increased risk of QT interval prolongation and ventricular arrhythmias including torsade de pointes should also be considered. There have been postmarketing reports of torsade de pointes associated with immediate-release trazodone following overdose and in the presence of multiple confounding factors, even at dosages of 100 mg/day or less. Moreover, some of the potent CYP450 3A4 inhibitors such as clarithromycin, erythromycin, telithromycin, lopinavir-ritonavir, saquinavir, and azole antifungal agents have also been reported to prolong the QT interval, thus additive effects may occur when used with trazodone.

MANAGEMENT: If concomitant use cannot be avoided, a lower dosage of trazodone should be considered during coadministration with a potent CYP450 3A4 inhibitor. Pharmacologic response to trazodone should be monitored more closely whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy, and the trazodone dosage adjusted as necessary. Patients should seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitations, irregular heartbeat, shortness of breath, or syncope.

References

  1. (2001) "Product Information. Desyrel (trazodone)." Bristol-Myers Squibb
  2. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical
  3. (2001) "Product Information. Crixivan (indinavir)." Merck & Co., Inc
  4. Mazur A, Strasberg B, Kusniec J, Sclarovsky S (1995) "QT prolongation and polymorphous ventricular tachycardia associated with trasodone-amiodarone combination." Int J Cardiol, 52, p. 27-9
  5. (2001) "Product Information. Viracept (nelfinavir)." Agouron Pharma Inc
  6. (2001) "Product Information. Agenerase (amprenavir)." Glaxo Wellcome
  7. Goodnick PJ, Jerry J, Parra F (2002) "Psychotropic drugs and the ECG: focus on the QTc interval." Expert Opin Pharmacother, 3, p. 479-98
  8. Greenblatt DJ, von Moltke LL, Harmatz JS, et al. (2003) "Short-term exposure to low-dose ritonavir impairs clearance and enhances adverse effects of trazodone." J Clin Pharmacol, 43, p. 414-22
  9. (2003) "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb
  10. (2003) "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline
  11. Levenson JL (1999) "Prolonged QT interval after trazodone overdose." Am J Psychiatry, 156, p. 969-70
  12. (2006) "Product Information. Prezista (darunavir)." Ortho Biotech Inc
  13. Dattilo PB, Nordin C (2007) "Prolonged QT associated with an overdose of trazodone." J Clin Psychiatry, 68, p. 1309-10
  14. (2012) "Product Information. Stribild (cobicistat/elvitegravir/emtricitabine/tenofov)." Gilead Sciences
  15. (2012) "Product Information. Oleptro (trazodone)." Labopharm Inc
View all 15 references

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Drug and food interactions

Moderate

traZODone food

Applies to: Desyrel (trazodone)

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

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
View all 4 references

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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 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

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

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