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Drug Interactions between donepezil and mefloquine

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

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Interactions between your drugs

Moderate

mefloquine donepezil

Applies to: mefloquine and donepezil

MONITOR: Since acetylcholinesterase inhibitors can cause bradycardia and heart block due to vagotonic effects on the sinoatrial and atrioventricular nodes, additive effects may occur with other agents that also possess bradycardic effects such as beta-blockers, calcium channel blockers, digitalis, some protease inhibitors (atazanavir, lopinavir-ritonavir, saquinavir), amiodarone, dronedarone, moricizine, lacosamide, and mefloquine. A group of French investigators conducted a retrospective analysis of spontaneous reports in the French Pharmacovigilance Database concerning adverse drug reactions (ADRs) associated with use of the acetylcholinesterase inhibitors donepezil, galantamine, and rivastigmine. Two hundred and five cases of potential drug-drug interaction with bradycardic drugs (beta-blockers, calcium channel blockers, amiodarone, digoxin) were identified, 73 of which were associated with serious ADRs including five deaths due to syncope, bradycardia, arrhythmia, or cardiac arrest. However, no details on the individual cases such as patient characteristics or concomitant risk factors were provided, making the contribution of a potential drug interaction difficult to evaluate. The remainder of the cases were of no apparent clinical consequences. In contrast, a phase III trial of donepezil consisting of 1035 patients reported no significant increase in risk ratios for bradycardia during concomitant use of beta-blockers, nondihydropyridine calcium channel blockers, or digoxin.

MANAGEMENT: Caution is advised if acetylcholinesterase inhibitors are used concomitantly with bradycardic drugs. Patients with underlying structural heart disease, preexisting conduction system abnormalities, ischemic heart disease, or cardiomyopathies may be at increased risk for developing cardiac conduction disturbances and atrioventricular block. Patients should be advised to notify their physician if they experience dizziness, lightheadedness, fainting, or irregular heartbeat.

References

  1. (2001) "Product Information. Cognex (tacrine)." Parke-Davis
  2. (2001) "Product Information. Aricept (donepezil)." Pfizer U.S. Pharmaceuticals
  3. (2001) "Product Information. Exelon (rivastigmine)." Novartis Pharmaceuticals
  4. (2005) "Product Information. Razadyne (galantamine)." Johnson and Johnson Medical Inc
  5. Tavassoli N, Sommet A, Lapeyre-Mestre M, Bagheri H, Montrastruc JL (2007) "Drug interactions with cholinesterase inhibitors : an analysis of the French pharmacovigilance database and a comparison of two national drug formularies (vidal, british national formulary)." Drug Saf, 30, p. 1063-71
  6. Tiseo PJ, Perdomo CA, Friedhoff LT (1998) "Concurrent administration of donepezil HCI and digoxin: assessment of pharmacokinetic changes." Br J Clin Pharmacol, 46(Suppl 1), p. 40-4
View all 6 references

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Drug and food interactions

Moderate

mefloquine food

Applies to: mefloquine

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of mefloquine. The proposed mechanism is increased drug solubility in the presence of food. In 20 healthy volunteers, administration of a single 750 mg oral dose of mefloquine 30 minutes following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of mefloquine by 73% and 40%, respectively, compared to administration in the fasting state. The Cmax and AUC of the carboxylic acid metabolite were also increased by 35% and 33%, respectively, compared to fasting. In addition, the time to reach peak plasma concentration (Tmax) of mefloquine was significantly shorter after food intake (17 hours) than in the fasting state (36 hours). There was no difference in the elimination half-life of mefloquine and metabolite, or the Tmax for the metabolite.

MANAGEMENT: To ensure maximal oral absorption, mefloquine should be administered immediately after a meal with at least 8 ounces of water.

References

  1. (2021) "Product Information. Mefloquine Hydrochloride (mefloquine)." Hikma USA (formerly West-Ward Pharmaceutical Corporation)
  2. Schmidt LE, Dalhoff K (2002) "Food-drug interactions." Drugs, 62, p. 1481-502

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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.

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