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Drug Interactions between duloxetine and Paxlovid

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

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Interactions between your drugs

Moderate

ritonavir DULoxetine

Applies to: Paxlovid (nirmatrelvir / ritonavir) and duloxetine

MONITOR: Coadministration with inhibitors of CYP450 2D6 may increase the plasma concentrations of duloxetine, which is partially metabolized by the isoenzyme. According to the product labeling, concomitant use of duloxetine (40 mg once daily) with paroxetine (20 mg once daily) resulted in an approximately 60% increase in duloxetine systemic exposure (AUC), and greater degrees of inhibition are expected with higher dosages of paroxetine. Although not studied, a similar interaction should be anticipated with other potent CYP450 2D6 inhibitors such as fluoxetine or quinidine. Theoretically, high plasma levels of duloxetine may increase the risk of serious adverse effects such as hypertension, hypertensive crisis, increased heart rate, orthostatic hypotension, syncope, and serotonin syndrome. Serotonin syndrome is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Symptoms may include mental status changes such as irritability, altered consciousness, confusion, hallucinations, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea.

MANAGEMENT: Caution is advised if duloxetine is used in combination with CYP450 2D6 inhibitors, particularly potent ones like paroxetine, fluoxetine, or quinidine. Pharmacologic response to duloxetine should be monitored more closely whenever a CYP450 2D6 inhibitor is added to or withdrawn from therapy, and the dosage adjusted as necessary.

References (2)
  1. Skinner MH, Kuan HY, Pan A, et al. (2003) "Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers." Clin Pharmacol Ther, 73, p. 170-7
  2. (2004) "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company

Drug and food interactions

Moderate

ritonavir food

Applies to: Paxlovid (nirmatrelvir / 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)
  1. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical
Moderate

DULoxetine food

Applies to: duloxetine

GENERALLY AVOID: Use of duloxetine in conjunction with chronic alcohol consumption may potentiate the risk of liver injury. Duloxetine alone can increase serum transaminase levels. In clinical trials, 0.3% of patients discontinued duloxetine due to liver transaminase elevations. The median time to detection was about two months. Three duloxetine-treated patients had liver injury as manifested by transaminase and bilirubin elevations, with evidence of obstruction. Substantial intercurrent ethanol use was present in each of these cases, which may have contributed to the abnormalities observed. Duloxetine does not appear to enhance the central nervous system effects of alcohol. When duloxetine and ethanol were administered several hours apart so that peak concentrations of each would coincide, duloxetine did not increase the impairment of mental and motor skills caused by alcohol.

MANAGEMENT: Due to the risk of liver injury, patients prescribed duloxetine should be counseled to avoid excessive use of alcohol. Duloxetine should generally not be prescribed to patients with substantial alcohol use.

References (1)
  1. (2004) "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company

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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