Drug Interactions between atazanavir and selpercatinib
This report displays the potential drug interactions for the following 2 drugs:
- atazanavir
- selpercatinib
Interactions between your drugs
atazanavir selpercatinib
Applies to: atazanavir and selpercatinib
GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of selpercatinib, which is primarily metabolized by the isoenzyme. When selpercatinib was coadministered with multiple doses of itraconazole, a potent CYP450 3A4 inhibitor, selpercatinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 30% and 133%, respectively. Increased exposure to selpercatinib may increase the risk of serious adverse effects such as QT interval prolongation, liver transaminase and bilirubin elevations, hypertension, hemorrhage, edema, and hypersensitivity reactions (e.g., fever, rash, arthralgias/myalgias with concurrent decreased platelets or transaminitis).
MANAGEMENT: Concomitant use of selpercatinib with potent CYP450 3A4 inhibitors should generally be avoided. If coadministration is required, the manufacturer recommends decreasing the dosage of selpercatinib. Patients receiving selpercatinib 120 mg twice daily should have the dosage reduced to 40 mg twice daily, and those receiving 160 mg twice daily should have the dosage reduced to 80 mg twice daily. Close monitoring for adverse effects is advisable, including more frequent ECGs and laboratory monitoring of liver enzymes, bilirubin, electrolytes, glucose, and blood counts. Selpercatinib treatment should be discontinued, interrupted, or dosage reduced in patients with serious or life-threatening toxicities in accordance with the product labeling. After the inhibitor has been discontinued for 3 to 5 elimination half-lives, the selpercatinib dosage that was taken prior to initiating the inhibitor may be resumed.
References
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2020) "Product Information. Retevmo (selpercatinib)." Lilly, Eli and Company
Drug and food interactions
selpercatinib food
Applies to: selpercatinib
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of selpercatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors. When selpercatinib was coadministered with multiple doses of itraconazole, a potent CYP450 3A4 inhibitor, selpercatinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 30% and 133%, respectively. Based on pharmacokinetic modeling, administration of selpercatinib with multiple doses of the moderate CYP450 3A4 inhibitors diltiazem, fluconazole, or verapamil is predicted to increase selpercatinib Cmax by 46% to 76% and AUC by 60% to 99%. 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. Increased exposure to selpercatinib may increase the risk of serious adverse effects such as QT interval prolongation, liver transaminase and bilirubin elevations, hypertension, hemorrhage, edema, and hypersensitivity reactions (e.g., fever, rash, arthralgias/myalgias with concurrent decreased platelets or transaminitis).
MANAGEMENT: Patients should limit or avoid consumption of grapefruit and grapefruit juice during treatment with selpercatinib.
References
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2020) "Product Information. Retevmo (selpercatinib)." Lilly, Eli and Company
atazanavir food
Applies to: atazanavir
ADJUST DOSING INTERVAL: Administration of atazanavir with food enhances oral bioavailability and reduces pharmacokinetic variability. According to the manufacturer, administration with a light meal increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single 400 mg dose of atazanavir by 57% and 70%, respectively, relative to the fasting state. Administration with a high-fat meal resulted in a mean increase of 35% in atazanavir AUC and no change in Cmax compared to fasting. The coefficient of variation of AUC and Cmax decreased by approximately one-half when given with either a light or high-fat meal compared to the fasting state.
MANAGEMENT: To ensure maximal oral absorption, atazanavir should be administered with or immediately after a meal.
References
- (2003) "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb
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
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
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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