MALARONE- atovaquone and proguanil hydrochloride tablet, film coated
GlaxoSmithKline LLC
1 INDICATIONS AND USAGE
1.1 Prevention of Malaria
MALARONE� is indicated for the prophylaxis of Plasmodium falciparum malaria, including in areas where chloroquine resistance has been reported.
1.2 Treatment of Malaria
MALARONE is indicated for the treatment of acute, uncomplicated P. falciparum malaria. MALARONE has been shown to be effective in regions where the drugs chloroquine, halofantrine, mefloquine, and amodiaquine may have unacceptable failure rates, presumably due to drug resistance.
2 DOSAGE AND ADMINISTRATION
The daily dose should be taken at the same time each day with food or a milky drink. In the event of vomiting within 1 hour after dosing, a repeat dose should be taken.
MALARONE may be crushed and mixed with condensed milk just prior to administration to patients who may have difficulty swallowing tablets.
2.1 Prevention of Malaria
Start prophylactic treatment with MALARONE 1 or 2 days before entering a malaria?endemic area and continue daily during the stay and for 7 days after return.
Adults
One MALARONE Tablet (adult strength = 250 mg atovaquone/100 mg proguanil hydrochloride) per day. Treatment of Acute Malaria
Adults
Four MALARONE Tablets (adult strength; total daily dose 1 g atovaquone/400 mg proguanil hydrochloride) as a single daily dose for 3 consecutive days.
Pediatric Patients
The dosage for treatment of acute malaria in pediatric patients is based upon body weight. Renal Impairment
Do not use MALARONE for malaria prophylaxis in patients with severe renal impairment (creatinine clearance <30 mL/min) [see Contraindications (4.2)]. Use with caution for the treatment of malaria in patients with severe renal impairment, only if the benefits of the 3-day treatment regimen outweigh the potential risks associated with increased drug exposure. No dosage adjustments are needed in patients with mild (creatinine clearance 50 to 80 mL/min) or moderate (creatinine clearance 30 to 50 mL/min) renal impairment. [See Clinical Pharmacology (12.3).]
3 DOSAGE FORMS AND STRENGTHS
Each MALARONE Tablet (adult strength) contains 250 mg atovaquone and 100 mg proguanil hydrochloride. MALARONE Tablets are pink, film?coated, round, biconvex tablets engraved with �GX CM3" on one side.
Each MALARONE Pediatric Tablet contains 62.5 mg atovaquone and 25 mg proguanil hydrochloride. MALARONE Pediatric Tablets are pink, film?coated, round, biconvex tablets engraved with �GX CG7" on one side. DESCRIPTION
MALARONE (atovaquone and proguanil hydrochloride) Tablets (adult strength) and MALARONE (atovaquone and proguanil hydrochloride) Pediatric Tablets, for oral administration, contain a fixed?dose combination of the antimalarial agents atovaquone and proguanil hydrochloride.
The chemical name of atovaquone is trans -2-[4-(4-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthalenedione. Atovaquone is a yellow crystalline solid that is practically insoluble in water. It has a molecular weight of 366.84 and the molecular formula C22 H19 ClO3 Mechanism of Action
The constituents of MALARONE, atovaquone and proguanil hydrochloride, interfere with 2 different pathways involved in the biosynthesis of pyrimidines required for nucleic acid replication. Atovaquone is a selective inhibitor of parasite mitochondrial electron transport. Proguanil hydrochloride primarily exerts its effect by means of the metabolite cycloguanil, a dihydrofolate reductase inhibitor. Inhibition of dihydrofolate reductase in the malaria parasite disrupts deoxythymidylate synthesis.