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Drug Interactions between Gilenya and Quin-G

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

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Interactions between your drugs

Major

quiNIDine fingolimod

Applies to: Quin-G (quinidine) and Gilenya (fingolimod)

CONTRAINDICATED: Theoretical concerns exist that initiating treatment with fingolimod may potentiate the risk of torsade de pointes arrhythmia associated with the use of class IA (e.g., disopyramide, quinidine, procainamide) and class III (e.g., amiodarone, dofetilide, ibutilide, sotalol) antiarrhythmic agents. Fingolimod can cause a decrease in heart rate during initiation of therapy that is apparent within an hour of the first dose and maximal at approximately 6 hours postdose in most cases, but occasionally up to 20 hours after the first dose. Further, but smaller decreases in heart rate may occur after the second dose, although heart rate eventually returns to baseline within one month of chronic treatment. The mean decrease in heart rate in patients receiving fingolimod 0.5 mg at 6 hours after the first dose was approximately 13 beats per minute (bpm). Heart rates below 40 bpm were rarely observed. In controlled clinical trials, adverse reactions of symptomatic bradycardia (hypotension, dizziness, fatigue, palpitations, chest pain) following the first dose were reported in 0.5% of patients receiving fingolimod 0.5 mg, compared to no patient on placebo. Initiation of fingolimod treatment has also resulted in transient AV conduction delays. First- and second-degree AV block (prolonged PR interval on ECG) following the first dose were each reported in 0.1% of patients receiving fingolimod 0.5 mg, compared to no patient on placebo. In a study of 698 patients with available 24-hour Holter monitoring data after their first dose, second degree AV blocks, usually Mobitz type I (Wenckebach), were reported in 3.7% of patients receiving fingolimod 0.5 mg and 2% of patients receiving placebo. Bradycardia and conduction abnormalities were usually transient and asymptomatic, and resolved within the first 24 hours on treatment, but they occasionally required treatment with atropine or isoproterenol.

MANAGEMENT: The use of fingolimod in patients with arrhythmias requiring treatment with class IA or class III antiarrhythmic agents has not been studied and is considered contraindicated.

References

  1. "Product Information. Gilenya (fingolimod)." Novartis Pharmaceuticals (2010):
  2. FDA. U.S. Food and Drug Administration "FDA Drug Safety Communication: Revised recommendations for cardiovascular monitoring and use of multiple sclerosis drug Gilenya (fingolimod). http://www.fda.gov/Drugs/DrugSafety/ucm303192.htm#data" (2012):

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Drug and food interactions

Moderate

quiNIDine food

Applies to: Quin-G (quinidine)

GENERALLY AVOID: In a small, randomized, crossover study, the administration of quinidine with grapefruit juice (compared to water) to healthy volunteers significantly prolonged the time to reach peak plasma quinidine concentrations and decreased the plasma concentrations of its major metabolite, 3-hydroxyquinidine. These changes were associated pharmacodynamically with both a delay and a reduction in the maximal effect on QTc interval. The proposed mechanism is delay of gastric emptying as well as inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits.

MANAGEMENT: Given the drug's narrow therapeutic index, patients receiving quinidine therapy should avoid the consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels.

References

  1. Ace LN, Jaffe JM, Kunka RL "Effect of food and an antacid on quinidine bioavailability." Biopharm Drug Dispos 4 (1983): 183-90
  2. Min DI, Ku YM, Geraets DR, Lee HC "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol 36 (1996): 469-76
  3. Ha HR, Chen J, Leuenberger PM, Freiburghaus AU, Follah F "In vitro inhibition of midazolam and quinidine metabolism by flavonoids." Eur J Clin Pharmacol 48 (1995): 367-71
  4. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77
View all 4 references

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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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.