Atovaquone and proguanil

Malarone

01Approved uses

• prophylaxis of Plasmodium falciparum (P. falciparum) malaria, including in areas where chloroquine resistance has been reported.
• treatment of acute, uncomplicated P. falciparum malaria.

02Forms and strengths

• Tablets (adult strength): 250 mg atovaquone and 100 mg proguanil hydrochloride.
• Pediatric tablets: 62.5 mg atovaquone and 25 mg proguanil hydrochloride.

03How it is taken

• MALARONE should be taken with food or a milky drink.
• Start prophylaxis 1 or 2 days before entering a malaria‑endemic area and continue daily during the stay and for 7 days after return.
• Adults: One adult strength tablet per day.
• Pediatric Patients: Dosage based on body weight (see Table 1).
• Adults: Four adult strength tablets as a single daily dose for 3 days.
• Pediatric Patients: Dosage based on body weight (see Table 2).

04Must not be used when

• Known serious hypersensitivity reactions to atovaquone or proguanil hydrochloride or any component of the formulation.
• Prophylaxis of P. falciparum malaria in patients with severe renal impairment (creatinine clearance <30 mL/min).

05Interactions

• Administration with rifampin or rifabutin is known to reduce atovaquone concentrations; concomitant use with MALARONE is not recommended.
• Proguanil may potentiate anticoagulant effect of warfarin and other coumarin-based anticoagulants. Caution advised when initiating or withdrawing MALARONE in patients on anticoagulants; coagulation tests should be closely monitored.
• Tetracycline may reduce atovaquone concentrations; parasitemia should be closely monitored.

06Warnings and precautions

• Atovaquone absorption may be reduced in patients with diarrhea or vomiting. If used in patients who are vomiting, parasitemia should be closely monitored and the use of an antiemetic considered. In patients with severe or persistent diarrhea or vomiting, alternative antimalarial therapy may be required.
• In mixed P. falciparum and Plasmodium vivax (P. vivax) infection, P. vivax relapse occurred commonly when patients were treated with MALARONE alone.
• In the event of recrudescent P. falciparum infections after treatment or prophylaxis failure, patients should be treated with a different blood schizonticide.
• Elevated liver laboratory tests and cases of hepatitis and hepatic failure requiring liver transplantation have been reported with prophylactic use.
• Severe Cutaneous Adverse Reactions (SCARs): Cases of SCARs such as Stevens‑Johnson syndrome (SJS) have been reported. SCARs can be life‑threatening or fatal. If symptoms or signs of SCARs develop, discontinue MALARONE immediately and institute appropriate therapy.
• MALARONE has not been evaluated for the treatment of cerebral malaria or other severe manifestations of complicated malaria. Patients with severe malaria are not candidates for oral therapy.

07Common side effects

• Most common treatment‑emergent adverse events with MALARONE were abdominal pain (13%), headache (13%), and cough (10%).

08Pregnancy

Available data from published literature and postmarketing experience with use of MALARONE in pregnant women are insufficient to identify a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. The proguanil component of MALARONE acts to inhibit parasitic dihydrofolate reductase; however, pregnant women and females of reproductive potential should continue folate supplementation to prevent neural tube defects.

09How it acts

MALARONE, a fixed-dose combination of atovaquone and proguanil hydrochloride, is an antimalarial agent.

This section reports the approved product information. The wording is condensed from the regulator's own summary, and the full document is linked under Sources.