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Drug Interactions between Agamree and fingolimod

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

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Interactions between your drugs

Major

fingolimod vamorolone

Applies to: fingolimod and Agamree (vamorolone)

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 (5)
  1. (2010) "Product Information. Gilenya (fingolimod)." Novartis Pharmaceuticals
  2. (2023) "Product Information. Fingolimod (fingolimod)." Dr Reddy's Laboratories (UK) Ltd
  3. (2023) "Product Information. Fingolimod (Teva) (fingolimod)." Teva Pharma Australia Pty Ltd, 1.0
  4. (2023) "Product Information. Fingolimod (fingolimod)." Apotex Corporation
  5. (2023) "Product Information. Apo-Fingolimod (fingolimod)." Apotex Inc

Drug and food interactions

Moderate

vamorolone food

Applies to: Agamree (vamorolone)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of vamorolone. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism in the gut wall by certain compounds present in grapefruit. The metabolism of vamorolone is mediated by the isoenzymes CYP450 3A4/5, and CYP450 2C8, and uridine diphosphate glucuronosyltransferases (UGT) 1A3, 2B7, and 2B17. 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 systemic exposure to vamorolone may increase the risk of corticosteroid adverse effects such as hypercorticism, hyperglycemia, adrenal suppression, immunosuppression, hypertension, salt and water retention, electrolyte abnormalities, behavioral and mood disturbances, posterior subcapsular cataracts, glaucoma, bone loss, and growth retardation in children and adolescents.

MANAGEMENT: Until further information is available, it may be advisable for patients to avoid the consumption of large amounts of grapefruit and grapefruit juice during vamorolone therapy unless otherwise directed by their doctor, as the interaction is unreliable and subject to a high degree of interpatient variation. If coadministration is considered necessary, patients should be closely monitored for signs and symptoms of corticosteroid adverse effects. Patients should also be monitored for signs and symptoms of hypercorticism such as acne, striae, thinning of the skin, easy bruising, moon facies, dorsocervical "buffalo" hump, truncal obesity, increased appetite, acute weight gain, edema, hypertension, hirsutism, hyperhidrosis, proximal muscle wasting and weakness, glucose intolerance, exacerbation of preexisting diabetes, and depression. Signs and symptoms of adrenal insufficiency include anorexia, hypoglycemia, nausea, vomiting, weight loss, muscle wasting, fatigue, weakness, dizziness, postural hypotension, depression, and adrenal crisis manifested as an inability to respond to stress (e.g., illness, infection, surgery, trauma). Consultation with product labeling for specific recommendations is advisable.

References (30)
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  8. Finkenbine RD, Frye MD (1998) "Case of psychosis due to prednisone-clarithromycin interaction." Gen Hosp Psychiat, 20, p. 325-6
  9. Varis T, Kaukonen KM, Kivisto KT, Neuvonen PJ (1998) "Plasma concentrations and effects of oral methylprednisolone are considerably increased by itraconazole." Clin Pharmacol Ther, 64, p. 363-8
  10. Hillebrand-Haverkort ME, Prummel MF, ten Veen JH (1999) "Ritonavir-induced Cushing's syndrome in a patient treated with nasal fluticasone." AIDS, 13, p. 1803
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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.

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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.

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