Drug Interactions between avapritinib and fingolimod
This report displays the potential drug interactions for the following 2 drugs:
- avapritinib
- fingolimod
Interactions between your drugs
fingolimod avapritinib
Applies to: fingolimod and avapritinib
MONITOR CLOSELY: Coadministration of fingolimod with antineoplastic, immunosuppressive, or other immune-modulating therapies is expected to increase the risk of immunosuppression and infection. Life-threatening and sometimes fatal infections have been reported. Fingolimod causes reversible sequestration of lymphocytes in lymphoid tissues. When administered daily, fingolimod produces a dose-dependent reduction in peripheral lymphocyte count to 20-30% of baseline values, which may increase the risk of infections. In Phase III clinical trials, short courses of corticosteroids (up to 5 days) to treat relapses did not increase the overall rate of infection and so is generally considered acceptable during treatment with fingolimod. A small study of 12 subjects receiving fingolimod 0.5 mg daily found that the lymphocyte count decreased to approximately 60% of baseline within 4 to 6 hours after the first dose. The lymphocyte count continued to decrease over a 2-week period, reaching a nadir count of approximately 500 cells/mcL (30% of baseline). In a placebo-controlled study of 1272 multiple sclerosis (MS) patients, 18% of patients on fingolimod 0.5 mg daily (n = 425) reached a nadir of less than 200 cells/mcL on at least one occasion, compared to no patient on placebo (n = 418). Chronic fingolimod dosing leads to a mild decrease in the neutrophil count to approximately 80% of baseline but does not affect monocytes. Decreased lymphocyte counts persist during daily dosing, then generally return to baseline within 1 to 2 months after stopping the medication.
MANAGEMENT: The safety and efficacy of fingolimod in combination with antineoplastic, immunosuppressive, or immune-modulating agents have not been evaluated. Concomitant use is considered contraindicated by some authorities; however, short courses of corticosteroids (up to 5 days) are generally considered acceptable during treatment with fingolimod. A complete blood count is recommended prior to starting fingolimod if a recent one (i.e., within the last 6 months or after discontinuation of prior therapy) is not available. Treatment suspension should be considered in patients who develop a serious infection, and the benefits and risks reassessed prior to restarting treatment. Patients should be instructed to immediately report any signs or symptoms of an infection (e.g., fever, body aches, chills, nausea, vomiting, headache with neck stiffness or confusion) to their doctor. Because fingolimod remains in the blood for up to two months after the last dose, continued monitoring is recommended throughout this period, and initiating other drugs during this period warrants the same considerations needed for concomitant administration. Consult the manufacturer's product labeling for specific recommendations regarding the timing of use of fingolimod in relation to other agents used in the treatment of MS, including beta interferon, glatiramer acetate, dimethyl fumarate, alemtuzumab, teriflunomide, and mitoxantrone.
References
- (2010) "Product Information. Gilenya (fingolimod)." Novartis Pharmaceuticals
- (2023) "Product Information. Fingolimod (fingolimod)." Dr Reddy's Laboratories (UK) Ltd
- (2023) "Product Information. Fingolimod (Teva) (fingolimod)." Teva Pharma Australia Pty Ltd, 1.0
- (2023) "Product Information. Fingolimod (fingolimod)." Apotex Corporation
- (2023) "Product Information. Apo-Fingolimod (fingolimod)." Apotex Inc
Drug and food interactions
avapritinib food
Applies to: avapritinib
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of avapritinib. 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. Based on pharmacokinetic modeling, administration of avapritinib (300 mg once daily) in combination with the potent CYP450 3A4 inhibitor itraconazole (200 mg once daily) is predicted to increase avapritinib systemic exposure (AUC) by 600% at steady state, while administration with the moderate CYP450 3A4 inhibitor fluconazole (200 mg once daily) is predicted to increase avapritinib systemic exposure (AUC) by 210% at steady state. 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 avapritinib may increase the risk and/or severity of serious adverse effects such as intracranial hemorrhage, cognitive impairment, mood disorders, hallucinations, edema, and decreases in hemoglobin, leukocytes, neutrophils, and platelets.
ADJUST DOSING INTERVAL: Food may increase the oral absorption of avapritinib. When avapritinib was administered with a high-calorie, high-fat meal (approximately 909 calories; 58 g carbohydrate, 56 g fat, 43 g protein), avapritinib Cmax and AUC increased by 59% and 29%, respectively, compared to administration in the fasted state.
MANAGEMENT: Avapritinib should be administered on an empty stomach at least 1 hour before or 2 hours after a meal. Patients should avoid consumption of grapefruit and grapefruit juice during treatment with avapritinib.
References
- (2020) "Product Information. Ayvakit (avapritinib)." Blueprint Medicines Corporation
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
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