MALARONE PEDIATRIC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MALARONE PEDIATRIC (MALARONE PEDIATRIC).
MALARONE PEDIATRIC is a fixed-dose combination of atovaquone and proguanil. Atovaquone selectively inhibits the mitochondrial electron transport chain of Plasmodium species at the cytochrome bc1 complex, collapsing mitochondrial membrane potential and disrupting pyrimidine synthesis. Proguanil is a prodrug converted to cycloguanil, which inhibits dihydrofolate reductase in the parasite, blocking DNA synthesis. The combination synergistically kills blood-stage schizonts and inhibits liver-stage hypnozoites of P. falciparum.
| Metabolism | Atovaquone undergoes minimal metabolism, with glucuronidation as a minor pathway, and is primarily excreted unchanged in feces. Proguanil is hepatically metabolized via CYP2C19 to its active metabolite cycloguanil, and to a lesser extent by CYP3A4. |
| Excretion | Atovaquone: >90% excreted unchanged in feces via biliary elimination; <1% renal. Proguanil: ~40-60% excreted renally as unchanged drug and active metabolite cycloguanil; ~30% fecal. |
| Half-life | Atovaquone: terminal half-life 1.5-3 days (range 2-3 days in adults, longer in children). Proguanil: terminal half-life 12-21 hours (parent drug) and 14-23 hours (cycloguanil). Clinically, atovaquone's long half-life supports single daily dosing. |
| Protein binding | Atovaquone: >99% bound to plasma proteins. Proguanil: ~75% bound to plasma proteins. |
| Volume of Distribution | Atovaquone: Vd ~0.6-1.0 L/kg (extensive tissue distribution). Proguanil: Vd ~0.2-0.5 L/kg. |
| Bioavailability | Atovaquone: Oral bioavailability highly variable (range 10-50%) but improved with fatty food; ~23% in fasted state, increased ~2-fold with high-fat meal. Proguanil: Oral bioavailability ~70-90%. |
| Onset of Action | Oral: Parasite clearance begins within 24-48 hours; clinical improvement typically observed within 24-72 hours. |
| Duration of Action | Oral: Prophylactic effect persists for 7 days after last dose due to atovaquone's long half-life. Treatment course is 3 consecutive days; repeat courses may be needed if vomiting occurs within 1 hour. |
Adults: 250 mg atovaquone/100 mg proguanil orally once daily for 3 consecutive days for treatment; for prophylaxis, 250 mg/100 mg orally once daily starting 1-2 days before travel and continued for 7 days after leaving endemic area.
| Dosage form | TABLET |
| Renal impairment | For prophylaxis: If CrCl 30-50 mL/min, reduce dose to half the standard adult dose; if CrCl <30 mL/min, use alternative agent. For treatment: If CrCl 30-50 mL/min, reduce dose to half the standard adult dose; if CrCl <30 mL/min, use alternative agent. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). For severe hepatic impairment (Child-Pugh C), use with caution due to limited data; no specific dose recommendation available. |
| Pediatric use | Children ≥5 kg: For treatment, 20 mg/kg atovaquone/8 mg/kg proguanil orally once daily for 3 days. For prophylaxis, 20 mg/kg atovaquone/8 mg/kg proguanil orally once daily. Dosing based on weight: 5-8 kg: pediatric tablet (62.5 mg/25 mg) daily; 9-10 kg: 1.5 pediatric tablets daily; 11-20 kg: 2 pediatric tablets daily; 21-30 kg: 3 pediatric tablets daily; 31-40 kg: 4 pediatric tablets daily; >40 kg: adult tablet (250 mg/100 mg) daily. |
| Geriatric use |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MALARONE PEDIATRIC (MALARONE PEDIATRIC).
| Breastfeeding | Atovaquone and proguanil are excreted in breast milk in low concentrations, but no adverse effects have been reported. M/P ratio not established. Consider risk-benefit; caution in infants with G6PD deficiency. Discontinue breastfeeding or drug if infant develops hemolysis. |
| Teratogenic Risk | MALARONE PEDIATRIC contains atovaquone and proguanil. Atovaquone is not teratogenic in animals, but proguanil is associated with increased risk of neural tube defects and other congenital anomalies if used in the first trimester. Data in humans are limited; it should only be used if benefit outweighs risk. Pregnancy category C. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to atovaquone, proguanil, or any component","Severe renal impairment (CrCl <30 mL/min) for prophylaxis","Concurrent use with rifampin or rifabutin (may reduce atovaquone levels)"]
| Precautions | ["Not recommended for severe malaria or cerebral malaria","May cause hypersensitivity reactions, including angioedema and anaphylaxis","Avoid in patients with severe renal impairment (CrCl <30 mL/min) due to risk of accumulation of proguanil","May cause hepatotoxicity; monitor liver function in prolonged use","May cause gastrointestinal disturbances; administer with food","Parasite resistance may develop; monitor for clinical failure"] |
Loading safety data…
| No specific dose adjustment required based on age alone; use standard adult dosing, but consider renal function as older adults may have reduced creatinine clearance. Monitor for adverse effects, particularly gastrointestinal. |
| Fetal Monitoring | Monitor for hemolysis in neonates with G6PD deficiency if maternal use late in pregnancy. No specific fetal monitoring required, but assess for congenital anomalies if first-trimester exposure. Monitor maternal liver function and blood counts periodically. |
| Fertility Effects | No evidence of impaired fertility in animal studies. No human data on effects on fertility. |