Label Changes for:

Lariam (mefloquine hydrochloride) 250 mg tablets

August 2009

Changes have been made to the WARNINGS, PRECAUTIONS and ADVERSE REACTIONS sections of the safety label.

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) -- August 2009

WARNINGS

  • Halofantrine should not be administered with Lariam or within 15 weeks of the last dose of Lariam due to the risk of a potentially fatal prolongation of the QTc interval.
  • Ketoconazole should not be administered with Lariam or within 15 weeks of the last dose of Lariam due to the risk of a potentially fatal prolongation of the QTc interval. Ketoconazole increases plasma concentrations and elimination half-life of mefloquine following coadministration

PRECAUTIONS

Central and Peripheral Nervous System Effects
  • vertigo
Information for Patients
  • that in a small percentage of cases, patients are unable to take this medication because of side effects, including vertigo
Drug Interactions
  • Halofantrine and Other Antimalarials
    • Halofantrine should not be administered with Lariam or within 15 weeks of the last dose of Lariam
  • Ketoconazole (potent inhibitor of CYP3A4)
    • Co-administration of a single 500 mg oral dose of Lariam with 400 mg of ketoconazole once daily for 10 days in 8 healthy volunteers resulted in a increase in the mean Cmax and AUC of mefloquine by 64% and 79%, respectively, and an increase in the mean elimination half-life of mefloquine from 322 hours to 448 hours. Ketoconazole should not be administered with Lariam or within 15 weeks of the last dose of Lariam due to the risk of a potentially fatal prolongation of the QTc interval.
  • Rifampin (Potent Inducer of CYP3A4)
    • Co-administration of a single 500 mg oral dose of Lariam and 600 mg of rifampin once daily for 7 days in 7 healthy Thai volunteers resulted in a decrease in the mean Cmax and AUC of mefloquine by 19% and 68%, respectively, and a decrease in the mean elimination half-life of mefloquine from 305 hours to 113 hours. Rifampin should be used cautiously in patients taking Lariam.
  • Inhibitors and Inducers of CYP3A4
    • Mefloquine does not inhibit or induce the CYP 450 enzyme system. Thus, concomitant administration of Lariam and substrates of the CYP 450 enzyme system is not expected to result in a drug interaction. However, co-administration of CYP 450 inhibitors or inducers may increase or decrease mefloquine plasma concentrations, respectively.
  • Substrates and Inhibitors of P-glycoprotein
    • It has been shown in vitro that mefloquine is a substrate and an inhibitor of P-glycoprotein. Therefore, drug-drug interactions could also occur with drugs that are substrates or are known to modify the expression of this transporter. The clinical relevance of these interactions is not known to date.
  • Other Potential Interactions
    • No other drug interactions are known. Nevertheless, the effects of Lariam on travelers receiving co-medication, particularly diabetics or patients using anticoagulants, should be checked before departure.
    • In clinical trials, the concomitant administration of sulfadoxine and pyrimethamine did not alter the
      adverse reaction profile of mefloquine.

ADVERSE REACTIONS

Postmarketing
  • Occasionally, more severe neuropsychiatric disorders have been reported such as: mood swings, memory impairment (no new change, reworded)
  • Other less frequently reported adverse events:
    • Cardiovascular Disorders: irregular heart rate
    • Other Symptoms: hyperhidrosis
Laboratory
  • Lariam may occur or persist up to several weeks after discontinuation of the drug (reworded)

MEDICATION GUIDE

  • The Medication Guide has been revised to incorporate the above safety information changes 
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