MALARONE

What it is

MALARONE is a fixed combination product containing atovaquone and proguanil hydrochloride. MALARONE TABLETS (250/100) contain atovaquone 250 mg and proguanil hydrochloride 100 mg, while MALARONE JUNIOR TABLETS (62.5/25) contain atovaquone 62.5 mg and proguanil hydrochloride 25 mg. The active ingredients interfere with two different pathways in the biosynthesis of pyrimidines, required for nucleic acid replication. Atovaquone works via inhibition of mitochondrial electron transport at the level of the cytochrome bc₁ complex, and collapse of mitochondrial membrane potential. Proguanil, via its metabolite cycloguanil, inhibits dihydrofolate reductase, which disrupts deoxythymidylate synthesis.

Approved indications

— Prophylaxis of *Plasmodium falciparum* malaria in adults and children ≥11 kg. — Treatment of *Plasmodium falciparum* malaria in adults and children aged 3 years or older.

Dosing overview

The daily dose should be taken with food or a milky drink at the same time each day. **Prophylaxis:** Prophylaxis should start 1 to 2 days before entering a malaria-endemic area, and be continued daily until seven days after leaving the area. For adults, the dose is one MALARONE TABLET (250/100) daily. For children, dosing is based on body weight: 11 to 20 kg requires 1 MALARONE JUNIOR TABLET (62.5/25); 21 to 30 kg requires 2 MALARONE JUNIOR TABLETS (62.5/25); 31 to 40 kg requires 3 MALARONE JUNIOR TABLETS (62.5/25); and >40 kg requires 1 MALARONE TABLET (250/100). **Treatment:** For adults, the treatment dose is four MALARONE TABLETS (250/100) as a single dose for three consecutive days. For children, the dose is based on body weight: 11 to 20 kg requires 1 MALARONE TABLET (250/100); 21 to 30 kg requires 2 MALARONE TABLETS (250/100); 31 to 40 kg requires 3 MALARONE TABLETS (250/100); and >40 kg requires 4 MALARONE TABLETS (250/100), each given as a single dosage for 3 consecutive days.

Key safety warnings

Cases of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS) and erythema multiforme (EM) have been reported in patients treated with MALARONE. As SCARs can be life-threatening or fatal, if signs and symptoms suggestive of SCARs appear, treatment with MALARONE must be discontinued immediately, and alternative treatment should be given. MALARONE has not been evaluated for the treatment of cerebral malaria or other severe manifestations of complicated malaria including hyperparasitaemia, pulmonary oedema or renal failure. Parasite relapse occurred commonly when *P. vivax* malaria was treated with MALARONE alone. Travellers with intense exposure to *P. vivax* or *P. ovale*, and those who develop malaria caused by either of these parasites, will require additional treatment with a drug such as primaquine, that is active against hypnozoites. Proguanil may potentiate the anticoagulant effect of warfarin and other coumarin based anticoagulants. Caution is advised when initiating or withdrawing malaria prophylaxis or treatment with MALARONE in patients on continuous treatment with coumarin based anticoagulants. Coadministration of efavirenz with MALARONE may result in a decrease in exposure to atovaquone and proguanil. When given with efavirenz or boosted protease-inhibitors, atovaquone concentrations have been observed to decrease as much as 75%. Since decreased concentrations of atovaquone and proguanil may result in a decrease of antimalarial efficacy, concomitant administration should be avoided whenever possible.

Contraindications

MALARONE is contraindicated in individuals with known hypersensitivity to atovaquone or proguanil hydrochloride or to any component of the formulation. MALARONE is contraindicated for prophylaxis of *P. falciparum* malaria in patients with severe renal impairment (creatinine clearance <30 mL/min).

Regulatory history

MALARONE TABLETS (250/100) was first listed on the ARTG on 4 May 1998. MALARONE JUNIOR TABLETS (62.5/25) was first listed on the ARTG on 26 March 2003.