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Drug Interactions between duloxetine and pexidartinib

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

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Interactions between your drugs

Major

DULoxetine pexidartinib

Applies to: duloxetine and pexidartinib

GENERALLY AVOID: Serious cases of hepatotoxicity, some fatal, have occurred in patients treated with pexidartinib. Concomitant use of other potentially hepatotoxic agents may potentiate the risk of liver injury. The mechanism of hepatotoxicity is unknown, its occurrence cannot be predicted, and it is unknown whether liver injury occurs in the absence of increased transaminases. In one study, 5% of patients who received pexidartinib developed signs of serious liver injury (elevated serum transaminases greater than 3 times the upper limit of normal (ULN) and total bilirubin greater than 2 times ULN). In these patients, peak ALT ranged from 6 to 9 times ULN, peak total bilirubin ranged from 2.5 to 15 times ULN, and ALP was greater than 2 times ULN. Liver transaminases and total bilirubin improved to less than 2 times ULN in these patients 1 to 7 months after discontinuing pexidartinib.

MANAGEMENT: The use of pexidartinib with other potentially hepatotoxic agents should be avoided. Patients treated with pexidartinib should have liver function tests, including AST, ALT, total bilirubin, direct bilirubin, ALP, and gamma-glutamyl transferase (GGT), prior to initiation of pexidartinib, weekly for the first 8 weeks, every 2 weeks for the next month, and every 3 months thereafter. Pexidartinib therapy may require a dosage reduction, to be withheld, or permanently discontinued based on the severity of the hepatotoxicity. A recurrence of increased serum transaminases, bilirubin, or ALP may occur upon rechallenge with a reduced dose of pexidartinib. Liver function tests should be performed weekly for the first month after rechallenge. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice.

References (1)
  1. (2019) "Product Information. Turalio (pexidartinib)." Daiichi Sankyo, Inc.

Drug and food interactions

Major

pexidartinib food

Applies to: pexidartinib

ADJUST DOSING INTERVAL: The presence of food may increase the absorption and toxicity of pexidartinib. Administration of pexidartinib with a high-fat meal increased peak plasma concentration (Cmax) and systemic exposure (AUC) by 100% and prolonged the time to reach peak plasma concentration (Tmax) by 2.5 hours.

GENERALLY AVOID: Grapefruit or grapefruit juice may increase the plasma concentration and risk of adverse effects of pexidartinib, including potentially fatal hepatotoxicity. The mechanism is inhibition of CYP450 3A4-mediated metabolism of pexidartinib by certain compounds present in grapefruits. Concomitant administration of itraconazole, a strong CYP450 3A4 inhibitor, increased pexidartinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 48% and 70%, respectively.

MANAGEMENT: Pexidartinib should be administered on an empty stomach, at least one hour before or two hours after a meal or snack. Consumption of grapefruit or grapefruit juice should generally be avoided during pexidartinib therapy. If concomitant use is unavoidable, the dose of pexidartinib should be reduced according to the manufacturer's recommendations. If concomitant use of grapefruit or grapefruit juice is discontinued, the dose of pexidartinib may be increased (after 3 plasma half-lives of a strong CYP450 3A4 inhibitor) to the dose that was used prior to consumption of grapefruit or grapefruit juice.

References (1)
  1. (2019) "Product Information. Turalio (pexidartinib)." Daiichi Sankyo, Inc.
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.

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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