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Drug Interactions between Oleptro and ombitasvir / paritaprevir / ritonavir

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

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Interactions between your drugs

Moderate

traZODone ritonavir

Applies to: Oleptro (trazodone) and ombitasvir / paritaprevir / ritonavir

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 Pharmacologic response to trazodone should be monitored more closely whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy, and the trazodone dosage adjusted as necessary.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: Oleptro (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

ritonavir food

Applies to: ombitasvir / paritaprevir / 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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Moderate

paritaprevir food

Applies to: ombitasvir / paritaprevir / ritonavir

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of ombitasvir, paritaprevir, ritonavir, and dasabuvir. Relative to fasting conditions, administration of ombitasvir, paritaprevir, ritonavir, and dasabuvir with a moderate-fat meal (approximately 600 Kcal; 20% to 30% calories from fat) increased the mean systemic exposure (AUC) by 82%, 211%, 49%, and 30%, respectively. Relative to fasting conditions, administration of ombitasvir, paritaprevir, ritonavir, and dasabuvir with a high-fat meal (approximately 900 Kcal; with 60% calories from fat) increased the mean AUC by 76%, 180%, 44%, and 22%, respectively.

MANAGEMENT: Ombitasvir/paritaprevir/ritonavir plus dasabuvir should always be administered with a meal. The fat or calorie content does not matter.

References

  1. (2022) "Product Information. Viekira Pak (dasabuvir/ombitasvir/paritaprev/ritonav)." AbbVie US LLC

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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

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