A direct health care professional communication (DHPC) released by Novartis in liaison with European medicines agency (EMA) and some of national competent authorities in Europe to disseminate important safety information pertaining to drug (fingolimod) induced liver injury to alert healthcare professionals for a careful benefit -risk analysis and early implementation of risk minimization measures for a better patient safety.

Fingolimod is a sphingosine 1-phosphate receptor modulating agent (an immunomodulator) used in the treatment of patients suffering from relapsing multiple sclerosis. Novartis is the marketing authorization holder for fingolimod with the brand name Gilenya.

Based on the periodical review of safety evidence, three case reports were identified with liver failure requiring liver transplant in patients who are treated with fingolimod. One case report demonstrates a strong causal relationship with fingolimod. As per the case data, clinically significant information was reported pertaining to the signs of liver injury which included elevated serum hepatic enzymes and elevated total bilirubin within the 10 days after the initial dose of fingolimod suggesting a reasonable temporal relationship.

Novartis stated that, ‚ÄĚduring clinical development of fingolimod, elevations 3-fold the upper limit of normal (ULN) or greater in alanine aminotransferase (ALT) were identified in 8.0% of adult patients treated with fingolimod 0.5 mg and elevations 5-fold the ULN occurred in 1.8% of patients treated with fingolimod.”

Elevated liver enzymes is very common adverse drug reaction for fingolimod and this drug is discontinued due to the seriousness and severity of cases and if the elevation exceeded 5 times the ULN and recurrence of elevated liver transaminase elevations occurred with rechallenge in some patients, suggesting a causal relationship to fingolimod.

Important information for health care professionals for minimizing this risk:

Hepatic enzyme increase is a very common adverse drug reaction of the product but due to the seriousness and the severity of recent reported cases, recommendations for discontinuation of the therapy and monitoring have been strengthened and clarified to minimize the risk of drug induced liver injury.

Discontinue fingolimod upon identification of signs and symptoms and check for bilirubin level and liver transaminase enzymes and perform liver function tests regularly until 2 months of discontinuation.

Resume the treatment only after establishing a plausible alternative etiology for the signs and symptoms of liver injury.

Marketing authorisation holder stated that the product information and the educational materials for Gilenya, including the checklist for prescribers will be updated to reflect these new recommendations.

Voluntary ADR reporting

Every medicinal product has both benefits and risks. There is no single pharmaceutical product which is completely free from side effects/adverse reactions. All health care professionals and consumers of pharmaceutical medicinal products are encouraged to be aware of this fact and observe/monitor for any possible adverse events, reactions, medication errors, or quality complaints of medicinal products and report the same to your respective national health authority. This would accumulate safety evidence for medicinal products which in turn help health authorities to take regulatory actions at the earliest possibility for a better patient safety.

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