Drug Interactions between Coartem and fingolimod
This report displays the potential drug interactions for the following 2 drugs:
- Coartem (artemether/lumefantrine)
- fingolimod
Interactions between your drugs
artemether fingolimod
Applies to: Coartem (artemether / lumefantrine) and fingolimod
MONITOR CLOSELY: Due to its significant bradycardic effects, the risk of QT prolongation and torsade de pointes arrhythmia may be increased during initiation of fingolimod treatment in patients receiving drugs that prolong the QT interval. 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 post-dose 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 and AV block were rarely observed. In a study evaluating the effect on QT interval of fingolimod 1.25 or 2.5 mg at steady-state, when a negative chronotropic effect of the drug was still present, fingolimod treatment resulted in a prolongation of the QTc, with an upper bound of the 90% confidence interval of 14.0 msec. There was no consistent signal of increased incidence of QTc outliers, either absolute or change from baseline, associated with fingolimod treatment. In clinical studies, investigators did not observed meaningful prolongation of the QT interval during fingolimod use, but patients at risk for QT prolongation were excluded. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).
MANAGEMENT: Fingolimod has not been studied in patients receiving drugs that can prolong the QT interval. Because bradycardia and AV block are recognized risk factors for QT prolongation and torsade de pointes arrhythmia, close monitoring is recommended during initiation of fingolimod treatment in patients receiving concomitant drugs that can prolong the QT interval, patients with significant QT prolongation (QTc >470 msec in females or >450 msec in males), or patients with relevant risk factors for QT prolongation (e.g., hypokalemia, hypomagnesemia, congenital QT prolongation). Overnight continuous ECG monitoring after the first dose is recommended in accordance with the product labeling. Fingolimod should not be given if baseline QTc interval is 500 msec or greater. The same precautions are applicable if, after the first month of treatment, fingolimod is discontinued for more than two weeks and then restarted, since the effects on heart rate and AV conduction may recur on reintroduction of fingolimod. Within the first 2 weeks of treatment, first-dose procedures are also recommended after interruption of one day or more; during week 3 and 4 of treatment, first-dose procedures are recommended after treatment interruption of more than 7 days.
References (5)
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
- Cerner Multum, Inc. "Australian Product Information."
- (2010) "Product Information. Gilenya (fingolimod)." Novartis Pharmaceuticals
- FDA. U.S. Food and Drug Administration (2012) 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
lumefantrine fingolimod
Applies to: Coartem (artemether / lumefantrine) and fingolimod
MONITOR CLOSELY: Due to its significant bradycardic effects, the risk of QT prolongation and torsade de pointes arrhythmia may be increased during initiation of fingolimod treatment in patients receiving drugs that prolong the QT interval. 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 post-dose 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 and AV block were rarely observed. In a study evaluating the effect on QT interval of fingolimod 1.25 or 2.5 mg at steady-state, when a negative chronotropic effect of the drug was still present, fingolimod treatment resulted in a prolongation of the QTc, with an upper bound of the 90% confidence interval of 14.0 msec. There was no consistent signal of increased incidence of QTc outliers, either absolute or change from baseline, associated with fingolimod treatment. In clinical studies, investigators did not observed meaningful prolongation of the QT interval during fingolimod use, but patients at risk for QT prolongation were excluded. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).
MANAGEMENT: Fingolimod has not been studied in patients receiving drugs that can prolong the QT interval. Because bradycardia and AV block are recognized risk factors for QT prolongation and torsade de pointes arrhythmia, close monitoring is recommended during initiation of fingolimod treatment in patients receiving concomitant drugs that can prolong the QT interval, patients with significant QT prolongation (QTc >470 msec in females or >450 msec in males), or patients with relevant risk factors for QT prolongation (e.g., hypokalemia, hypomagnesemia, congenital QT prolongation). Overnight continuous ECG monitoring after the first dose is recommended in accordance with the product labeling. Fingolimod should not be given if baseline QTc interval is 500 msec or greater. The same precautions are applicable if, after the first month of treatment, fingolimod is discontinued for more than two weeks and then restarted, since the effects on heart rate and AV conduction may recur on reintroduction of fingolimod. Within the first 2 weeks of treatment, first-dose procedures are also recommended after interruption of one day or more; during week 3 and 4 of treatment, first-dose procedures are recommended after treatment interruption of more than 7 days.
References (5)
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
- Cerner Multum, Inc. "Australian Product Information."
- (2010) "Product Information. Gilenya (fingolimod)." Novartis Pharmaceuticals
- FDA. U.S. Food and Drug Administration (2012) 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
Drug and food interactions
lumefantrine food
Applies to: Coartem (artemether / lumefantrine)
GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of artemether and lumefantrine. The mechanism is decreased clearance due to inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. High plasma levels of artemether and lumefantrine may increase the risk of QT interval prolongation and ventricular arrhythmias including torsade de pointes. In clinical trials, asymptomatic prolongation of the Fridericia-corrected QT interval (QTcF) by more than 30 msec from baseline was reported in approximately one-third of patients treated with artemether-lumefantrine, and prolongation by more than 60 msec was reported in more than 5% of patients. A few patients (0.4%) in the adult/adolescent population and no patient in the infant/children population experienced a QTcF greater than 500 msec. However, the possibility that these increases were disease-related cannot be ruled out. In a study of healthy adult volunteers, administration of the six-dose regimen of artemether-lumefantrine was associated with mean changes in QTcF from baseline of 7.45, 7.29, 6.12 and 6.84 msec at 68, 72, 96, and 108 hours after the first dose, respectively. There was a concentration-dependent increase in QTcF for lumefantrine. No subject had a greater than 30 msec increase from baseline nor an absolute increase to more than 500 msec.
ADJUST DOSING INTERVAL: Food enhances the oral absorption of artemether and lumefantrine. In healthy volunteers, the relative bioavailability of artemether increased by two- to threefold and that of lumefantrine by sixteenfold when administered after a high-fat meal as opposed to under fasted conditions.
MANAGEMENT: Patients receiving artemether-lumefantrine therapy should avoid the consumption of grapefruits and grapefruit juice. To ensure maximal oral absorption, artemether-lumefantrine should be taken with food. Inadequate food intake can increase the risk for recrudescence of malaria. Patients who are averse to food during treatment should be closely monitored and encouraged to resume normal eating as soon as food can be tolerated.
References (3)
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Cerner Multum, Inc. "Australian Product Information."
- (2009) "Product Information. Coartem (artemether-lumefantrine)." Novartis Pharmaceuticals
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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