Malarone(atovaquone/proguanil hydrochloride) - Drug SummaryGlaxoSmithKline LLC
Malarone
(atovaquone/proguanil hydrochloride)
 COMMON BRAND NAMES
Malarone Pediatric
THERAPEUTIC CLASS
Antiprotozoal agent/dihydrofolate reductase inhibitor
DEA CLASS
RX
ADULT DOSAGE & INDICATIONS
Malaria
Prophylaxis of Plasmodium falciparum Malaria, Including in Areas Resistant to Chloroquine:
1 adult strength tab (250mg/100mg) qd; start 1 or 2 days before entering a malaria-endemic area and continue daily during stay and for 7 days after return
Treatment of Acute, Uncomplicated P. falciparum Malaria:
4 adult strength tabs (1g/400mg) qd for 3 consecutive days
PEDIATRIC DOSAGE & INDICATIONS
Malaria
Prophylaxis of Plasmodium falciparum Malaria, Including in Areas Resistant to Chloroquine:
11-20kg:
1 pediatric tab (62.5mg/25mg) qd
21-30kg:
2 pediatric tabs (125mg/50mg) qd
31-40kg:
3 pediatric tabs (187.5mg/75mg) qd
>40kg:
1 adult strength tab (250mg/100mg) qd
Start 1 or 2 days before entering a malaria-endemic area and continue daily during stay and for 7 days after return
Treatment of Acute, Uncomplicated P. falciparum Malaria:
5-8kg:
2 pediatric tabs (125mg/50mg) qd
9-10kg:
3 pediatric tabs (187.5mg/75mg) qd
11-20kg:
1 adult strength tab (250mg/100mg) qd
21-30kg:
2 adult strength tabs (500mg/200mg) qd
31-40kg:
3 adult strength tabs (750mg/300mg) qd
>40kg:
4 adult strength tabs (1g/400mg) qd
Treat for 3 consecutive days
ADMINISTRATION
Oral route
Take at the same time each day w/ food or a milky drink.
Repeat dose in the event of vomiting w/in 1 hr after dosing.
May crush and mix w/ condensed milk just prior to administration for patients who may have difficulty swallowing tabs.
HOW SUPPLIED
Tab: (Atovaquone/Proguanil) 250mg/100mg (adult), 62.5mg/25mg (pediatric)
CONTRAINDICATIONS
Known hypersensitivity reactions to atovaquone or proguanil hydrochloride or any component of the formulation. For prophylaxis in patients w/ severe renal impairment (CrCl <30mL/min).
WARNINGS/PRECAUTIONS
Reduced atovaquone absorption in patients with diarrhea or vomiting; monitor for parasitemia and consider use of an antiemetic if vomiting occurs. Alternative antimalarial therapy may be required in patients with severe or persistent diarrhea or vomiting. In mixed P. falciparum and Plasmodium vivax infections, P. vivax parasite relapse occurred commonly when patients were treated with atovaquone-proguanil alone. Treat with a different blood schizonticide in the event of recrudescent P. falciparum infections after treatment or failure of chemoprophylaxis. Elevated liver lab tests and cases of hepatitis and hepatic failure requiring liver transplantation reported with prophylactic use. Patients with severe malaria are not candidates for oral therapy. Caution for the treatment of malaria in patients with severe renal impairment. Caution in elderly.
ADVERSE REACTIONS
Abdominal pain, headache, N/V, diarrhea, asthenia, anorexia, dizziness, dreams, insomnia, oral ulcers, cough, pruritus.
DRUG INTERACTIONS
Atovaquone: Decreased levels with rifampin or rifabutin; not recommended with rifampin or rifabutin. Decreased levels with tetracycline; monitor for parasitemia. Reduced bioavailability with metoclopramide; use only if other antiemetics are not available. Decreased indinavir trough concentrations; use caution. Proguanil: May potentiate anticoagulant effect of warfarin and other coumarin-based anticoagulants; use caution when initiating or withdrawing in patients on continuous treatment with coumarin-based anticoagulants, and closely monitor coagulation tests with concomitant use.
PREGNANCY AND LACTATION
Category C, caution in nursing.
MECHANISM OF ACTION
Atovaquone: Antiprotozoal; selective inhibitor of parasite mitochondrial electron transport. Proguanil: Dihydrofolate reductase inhibitor; disrupts deoxythymidylate synthesis.
PHARMACOKINETICS
Absorption: Atovaquone: Absolute bioavailability (23% with food). Distribution: Atovaquone: Vd=8.8L/kg; plasma protein binding (>99%). Proguanil: Vd=1617-2502L (patients >15 yrs of age with body weight 31-110kg), 462-966L (pediatric patients ≤15 yrs of age with body weight 11-56kg); plasma protein binding (75%); found in breast milk. Metabolism: Proguanil: via CYP2C19; cycloguanil and 4-chlorophenylbiguanide (metabolites). Elimination: Atovaquone: Feces (>94% unchanged), urine (<0.6%); T1/2=2-3 days (adults), 1-2 days (pediatrics). Proguanil: Urine (40-60%); T1/2=12-21 hrs (adults and pediatrics).
ASSESSMENT
Assess for severity of malaria, drug hypersensitivity, renal dysfunction, diarrhea, vomiting, pregnancy/nursing status, and possible drug interactions.
MONITORING
Monitor for clinical response, N/V, diarrhea, hepatic/renal dysfunction, hypersensitivity, and other adverse reactions. Monitor parasitemia in patients who are vomiting. Monitor for relapse of infection when patients are treated with atovaquone-proguanil alone. Closely monitor coagulation tests when concomitant use with warfarin and other coumarin-based anticoagulants.
PATIENT COUNSELING
Instruct that if a dose is missed, to take a dose as soon as possible and then to return to normal dosing schedule. Advise not to double the next dose if a dose is skipped. Counsel about serious adverse events associated with therapy (eg, hepatitis, severe skin reactions, neurological and hematological events). Instruct to consult physician regarding alternative forms of prophylaxis if prophylaxis is prematurely discontinued for any reason. Inform that protective clothing, insect repellents, and bednets are important components of malaria prophylaxis. Instruct to seek medical attention for any febrile illness that occurs during or after return from a malaria-endemic area. Discuss with pregnant women anticipating travel to malarious areas about the risks/benefits of such travel.
STORAGE
25°C (77°F); excursions permitted to 15-30°C (59-86°F).