proguanil hydrochloride 100 MG Oral Tablet

INDICATIONS AND USAGE 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. Atovaquone and proguanil hydrochloride tablets have 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.

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. 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 ( 2.1 ) : • 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 ( 2.2 ) : • 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 ( 2.3 ) : • 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. 2.1 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. Dosage for Prevention of Malaria in Pediatric Patients Weight (kg) Atovaquone/ Proguanil HCl Total Daily Dose Dosage Regimen 11-20 62.5 mg/25 mg 1 atovaquone and proguanil hydrochloride pediatric tablet daily 21-30 125 mg/50 mg 2 atovaquone and proguanil hydrochloride pediatric tablets as a single daily dose 31-40 187.5 mg/75 mg 3 atovaquone and proguanil hydrochloride pediatric tablets as a single daily dose > 40 250 mg/100 mg 1 atovaquone and proguanil hydrochloride tablet (adult strength) as a single daily dose 2.2 Treatment of Acute Malaria Adults Four atovaquone and proguanil hydrochloride 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 (Table 2). Table 2. Dosage for Treatment of Acute Malaria in Pediatric Patients Weight (kg) Atovaquone/ Proguanil HCl Total Daily Dose Dosage Regimen 5-8 125 mg/50 mg 2 atovaquone and proguanil hydrochloride pediatric tablets daily for 3 consecutive days 9-10 187.5 mg/75 mg 3 atovaquone and proguanil hydrochloride pediatric tablets daily for 3 consecutive days 11-20 250 mg/100 mg 1 atovaquone and proguanil hydrochloride tablet (adult strength) daily for 3 consecutive days 21-30 500 mg/200 mg 2 atovaquone and proguanil hydrochloride tablets (adult strength) as a single daily dose for 3 consecutive days 31-40 750 mg/300 mg 3 atovaquone and proguanil hydrochloride tablets (adult strength) as a single daily dose for 3 consecutive days > 40 1 g/400 mg 4 atovaquone and proguanil hydrochloride tablets (adult strength) as a single daily dose for 3 consecutive days 2.3 Renal Impairment Do not use atovaquone and proguanil hydrochloride tablets for malaria prophylaxis in patients with severe renal impairment (creatinine clearance < 30 mL/min) [see Contraindications (4) ] . 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) .]

WARNINGS 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. ( 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. ( 5.2 ) Elevated liver laboratory tests and cases of hepatitis and hepatic failure requiring liver transplantation have been reported with prophylactic use. ( 5.3 ) Atovaquone and proguanil hydrochloride 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. ( 5.4 ) 5.1 Vomiting and Diarrhea Absorption of atovaquone may be reduced in patients with diarrhea or vomiting. If atovaquone and proguanil hydrochloride is used in patients who are vomiting, parasitemia should be closely monitored and the use of an antiemetic considered. [See Dosage and Administration ( 2 ).] Vomiting occurred in up to 19% of pediatric patients given treatment doses of atovaquone and proguanil hydrochloride. In the controlled clinical trials, 15.3% of adults received an antiemetic when they received atovaquone/proguanil and 98.3% of these patients were successfully treated. In patients with severe or persistent diarrhea or vomiting, alternative antimalarial therapy may be required. 5.2 Relapse of Infection In mixed P. falciparum and Plasmodium vivax infections, P. vivax parasite relapse occurred commonly when patients were treated with atovaquone and proguanil hydrochloride alone. In the event of recrudescent P. falciparum infections after treatment with atovaquone and proguanil hydrochloride or failure of chemoprophylaxis with atovaquone and proguanil hydrochloride, patients should be treated with a different blood schizonticide. 5.3 Hepatotoxicity Elevated liver laboratory tests and cases of hepatitis and hepatic failure requiring liver transplantation have been reported with prophylactic use of atovaquone and proguanil hydrochloride. 5.4 Severe Cutaneous Adverse Reactions 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 atovaquone and proguanil hydrochloride [see Adverse Reactions (6.2)]. SCARs can be life-threatening or fatal. If symptoms or signs of SCARs develop, discontinue atovaquone and proguanil hydrochloride immediately and institute appropriate therapy. Patients who have developed SCARs with the use of atovaquone and proguanil hydrochloride must not receive atovaquone and proguanil hydrochloride [see Contraindications ( 4 )]. 5.5 Severe or Complicated Malaria Atovaquone and proguanil hydrochloride has not been evaluated for the treatment of cerebral malaria or other severe manifestations of complicated malaria, including hyperparasitemia, pulmonary edema, or renal failure. Patients with severe malaria are not candidates for oral therapy

CONTRAINDICATIONS • Atovaquone and proguanil hydrochloride tablets are contraindicated in individuals with known hypersensitivity reactions (e.g., anaphylaxis, erythema multiforme or Stevens-Johnson syndrome, angioedema, vasculitis) to atovaquone or proguanil hydrochloride or any component of the formulation. • Atovaquone and proguanil hydrochloride tablets are contraindicated for prophylaxis of P. falciparum malaria in patients with severe renal impairment (creatinine clearance < 30 mL/min) because of pancytopenia in patients with severe renal impairment treated with proguanil [see Use in Specific Populations (8.6) , Clinical Pharmacology (12.3) ] . • 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 < 30 mL/min). ( 4 )

Mechanism of Action Atovaquone and proguanil hydrochloride tablets, a fixed-dose combination of atovaquone and proguanil hydrochloride, are an antimalarial agent [see Microbiology (12.4) ] .