Proguanil

Atovaquone and proguanil hydrochloride tablets are an antimalarial indicated for: • prophylaxis of Plasmodium falciparum malaria, including in areas where chloroquine resistance has been reported. ( 1.1 ) • treatment of acute, uncomplicated P. falciparum malaria. ( 1.2 ) 1.1 Prevention of Malaria Atovaquone and proguanil hydrochloride tablets are indicated for the prophylaxis of Plasmodium falciparum malaria, including in areas where chloroquine resistance has been reported. 1.2 Treatment of Malaria Atovaquone and proguanil hydrochloride tablets are indicated for the treatment of acute, uncomplicated P. falciparum malaria. …

• 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
• Atovaquone and proguanil hydrochloride tablets may be crushed and mixed with condensed milk just prior to administration to patients who may have difficulty swallowing tablets. • Atovaquone and proguanil hydrochloride tablets should be taken with food or a milky drink
• Prophylaxis : • 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)
• Treatment : • Adults: Four adult strength tablets as a single daily dose for 3 days. • Pediatric Patients: Dosage based on body weight (see Table 2)
• Renal Impairment : • Do not use for prophylaxis of malaria in patients with severe renal impairment. • Use with caution for treatment of malaria in patients with severe renal impairment
• Prevention of Malaria Start prophylactic treatment with atovaquone and proguanil hydrochloride tablets 1 or 2 days before entering a malaria-endemic area and continue daily during the stay and for 7 days after return
• Adults One atovaquone and proguanil hydrochloride tablet (adult strength = 250 mg atovaquone/100 mg proguanil hydrochloride) per day
• Pediatric Patients The dosage
• For prevention of malaria
• In pediatric patients is based upon body weight (Table 1)
• Table 1. …

Each atovaquone and proguanil hydrochloride tablet (adult strength) contains 250 mg atovaquone USP and 100 mg proguanil hydrochloride USP. Atovaquone and proguanil hydrochloride tablets are pinkish brown to brown colored, circular, biconvex beveled edge, film-coated tablets with ‘404’ debossed on one side and ‘G’ debossed on the other side. …

• Prophylaxis of Malaria Safety and effectiveness have not been established
• In pediatric patients who weigh less than 11 kg
• The efficacy and safety of atovaquone and proguanil hydrochloride have been established for the prophylaxis of malaria in controlled trials involving
• Pediatric patients weighing 11 kg or more [see Clinical Studies ]
• Treatment of Malaria Safety and effectiveness have not been established
• In pediatric patients who weigh less than 5 kg. …

Clinical trials of atovaquone and proguanil hydrochloride did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, the higher systemic exposure to cycloguanil, and the greater frequency of concomitant disease or ot …

• Important Administration Instructions • Advise patients to take atovaquone and proguanil hydrochloride tablets at the same time each day with food or a milky drink [see Dosage and Administration ] . • Advise patients to take a repeat dose of atovaquone and proguanil hydrochloride if vomiting occurs within 1 hour after dosing [see Dosage and Administration ] . • Advise patients to take a dose as soon as possible if a dose is missed, then return to their normal dosing schedule
• However, if a dose is skipped, the patient should not double the next dose
• Severe Cutaneous Adverse Reactions (SCARs) Advise patients about the signs and symptoms of serious skin manifestations. …

• Known serious hypersensitivity reactions to atovaquone or proguanil hydrochloride or any component of the formulation. ( 4 ) • Prophylaxis of P. falciparum malaria in patients with severe renal impairment (creatinine clearance

• Administration with rifampin or rifabutin is known to reduce atovaquone concentrations; concomitant use with atovaquone and proguanil hydrochloride is not recommended. ( 7.1 ) • Proguanil may potentiate anticoagulant effect of warfarin and other coumarin-based anticoagulants. Caution advised when initiating or withdrawing atovaquone and proguanil hydrochloride in patients on anticoagulants; coagulation tests should be closely monitored. ( 7.2 ) • Tetracycline may reduce atovaquone concentrations; parasitemia should be closely monitored. …

• 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. ( 5.1 ) • In mixed P. falciparum and Plasmodium vivax infection, P. vivax relapse occurred commonly when patients were treated with atovaquone and proguanil hydrochloride alone. ( 5.2 ) • In the event of recrudescent P. falciparum infections after treatment or prophylaxis failure, patients should be treated with a different blood schizonticide. …

The following clinically significant adverse reactions are discussed in another section of the labeling: • Vomiting and Diarrhea [see Warnings and Precautions ( 5.1 )]. • Hepatotoxicity [see Warnings and Precautions ( 5.3 )]. • Severe Cutaneous Adverse Reactions [see Warnings and Precautions ( 5.4 )]. • Prophylaxis: Common adverse reactions (≥4%) in adults were diarrhea, dreams, oral ulcers, and headache; these events occurred in a similar or lower proportion of subjects receiving atovaquone and proguanil hydrochloride than an active comparator. Common adverse reactions (≥5%) in pediatric patients included abdominal pain, headache, cough, and vomiting. …

8.1 Pregnancy Risk Summary Available data from published literature and postmarketing experience with use of atovaquone and proguanil hydrochloride in pregnant women are insufficient to identify a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes . …

There is no information on overdoses of atovaquone and proguanil hydrochloride substantially higher than the doses recommended for treatment. There is no known antidote for atovaquone, and it is currently unknown if atovaquone is dialyzable. Overdoses up to 31,500 mg of atovaquone have been reported. In one such patient who also took an unspecified dose of dapsone, methemoglobinemia occurred. Rash has also been reported after overdose. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.