Guest Post
The European Medicines Agency (equivalent of the FDA in the US) states in the Gilenya prescribing info http://www.ema.europa.eu/docs/en_GB... (p. 7, read 30 June 2017): “ Pharmacokinetic interactions of other substances on fingolimod Fingolimod is metabolised mainly by CYP4F2. Other enzymes like CYP3A4 may also contribute to its metabolism. Co-administration of fingolimod with ketoconazole resulted in a 1.7-fold increase in fingolimod and fingolimod phosphate exposure (AUC). Caution should be exercised with substances that may inhibit CYP3A4 (protease inhibitors, azole antifungals, some macrolides such as clarithromycin or telithromycin).”
I was recently prescribed 1 tablet of an antifungal called Fluconazole by a doctor (not my gp or neuro). Because I remembered the warning from the European prescribing info, I had a look at the prescribing info in my G packet. Surprisingly, it did not mention any such thing. I brought up the question at the pharmacy when I went to pick up the medication and they got in contact with Novartis to find out more. The medical affairs officer at Novartis provided the following excerpt from micromedexsolutions.com:
Warning: Concurrent use of FINGOLIMOD and FLUCONAZOLE may result in increased risk of QT interval prolongation and torsade de pointes.
Clinical Management: Concomitant use of fingolimod and fluconazole may result in an increased risk of QT interval prolongation and torsade de pointes (Prod Info GILENYA(TM) oral capsules, 2012; Prod Info DIFLUCAN® IV injection oral suspension tablets, 2011). If coadministration is necessary, observe fluconazole-treated patients with continuous ECG monitoring overnight in a medical facility when initiating fingolimod therapy (Prod Info GILENYA(TM) oral capsules, 2012).
Onset: Not Specified
Severity: Major
Documentation: Fair
Probable Mechanism: additive QT interval prolonging effects
Summary: Fingolimod and fluconazole have been associated with an increased risk of QT interval prolongation (Prod Info GILENYA(TM) oral capsules, 2012; Prod Info DIFLUCAN® IV injection oral suspension tablets, 2011), and torsade de pointes (Prod Info DIFLUCAN® IV injection oral suspension tablets, 2011). Initiating fingolimod therapy may decrease heart rate and prolong the QT interval (Prod Info GILENYA(TM) oral capsules, 2012). Drugs that prolong the QT interval, such as fluconazole, may increase the risk of torsade de pointes in patients with bradycardia. Therefore, observe fluconazole-treated patients with continuous ECG monitoring overnight in a medical facility when initiating fingolimod therapy (Prod Info GILENYA(TM) oral capsules, 2012).
Reference(s): Product Information: DIFLUCAN(R) IV injection oral suspension tablets, fluconazole IV injection oral suspension tablets. Roerig (per FDA), New York, NY, Nov, 2011.
Product Information: GILENYA(TM) oral capsules, fingolimod oral capsules. Novartis Pharmaceuticals Corporation (Per Manufacturer), East Hanover , NJ, Apr, 2012.
A similar warning can be found here http://www.webmd.com/drugs/2/drug-1...
The medical affairs officer mentioned to the pharmacy that they would now consider re-introducing the warning in the prescribing info included in the G packet in my country.