Rifampicin
Severe
Database
Markedly reduced atovaquone levels
Avoid combination
Source: Kimi deep-research + Cla
Drug reference
Atovaquone + Proguanil
Antimalarial fixed-dose combination · Antimalarial
Also known as Malarone, atovaquone with proguanil hydrochloride
START
Prophylaxis: 1 tab/day from 1–2 d pre-travel
TYPICAL MAX
Treatment: 4 tablets once daily × 3 days
STOP IF
Severe hypersensitivity or significant hepatotoxicity
WATCH
Take with fatty food; renal function (prophylaxis CrCl <30)
CDSCO approvedSchedule HATC P01BB51
KDIGO 2024 + manufacturer label
- ONSET
- 2h · absorption
- PEAK
- 2d · atovaquone Tmax
- t½
- 2.5d · atovaquone t½
- DURATION
- 1d · once-daily
EXCRETION
Atovaquone biliary/faecal; proguanil renal
route + CYP
INTERACTIONS
1 major
SEVERE in our sources
PREGNANCY
Use only if essential and alternatives unsuitable (limited data).
FDA category + note
Top interactionssee all 5 →
- RifampicinSevereDatabaseKimi deep-research + Cla
Mechanism
Atovaquone collapses the parasite mitochondrial membrane potential by inhibiting the cytochrome bc1 complex; proguanil (via cycloguanil) inhibits dihydrofolate reductase and synergistically potentiates atovaquone — causal prophylactic and blood-schizonticidal activity against Plasmodium falciparum.
Indications
Prophylaxis of Plasmodium falciparum malariaTreatment of uncomplicated P. falciparum malaria
Dosing
- Adult
- Prophylaxis: 1 adult tablet (250 mg atovaquone/100 mg proguanil) PO once daily, from 1–2 days before travel until 7 days after leaving. Treatment: 4 adult tablets once daily for 3 days.
- Pediatric
- Weight-banded paediatric tablets (62.5/25 mg) once daily.
- Renal adjustment
- Prophylaxis contraindicated if CrCl <30; treatment use only if no alternative.
- Hepatic adjustment
- Caution; limited data in severe impairment.
- Geriatric
- No specific adjustment (assess renal function).
- Max dose
- Treatment: 4 adult tablets once daily for 3 days
Pharmacokinetics
Onset
Blood-schizonticidal over 1–3 days (treatment)
Peak effect
Atovaquone Tmax ~2–3 days (lipophilic); proguanil ~2–4 h
Duration
~24 h (once-daily)
Half-life
Atovaquone ~2–3 days; proguanil ~12–21 h
Bioavailability
Atovaquone improved with fatty food
Protein binding
Atovaquone >99%; proguanil ~75%
Metabolism
Proguanil via CYP2C19 to active cycloguanil; atovaquone minimal
Excretion
Atovaquone biliary/faecal; proguanil renal
Contraindications
- Prophylaxis if CrCl <30 mL/min (proguanil accumulation)
- Hypersensitivity to atovaquone or proguanil
- Caution: severe hepatic impairment
Side effects
Common
Abdominal painNausea/vomitingHeadacheDiarrhoeaMouth ulcers (treatment doses)
Serious
- Severe hypersensitivity (rare SJS)
- Hepatitis/transaminase elevation
- Anaphylaxis
Pregnancy & lactation
Pregnancy
Use only if essential and alternatives unsuitable (limited data).
Lactation
Avoid in infants <5 kg (limited data); otherwise weigh benefit/risk.
Drug interactions
Efavirenz
Moderate
Database
Reduced atovaquone levels
Avoid or monitor closely
Source: Kimi deep-research + Cla
Metoclopramide
Moderate
Database
Reduced atovaquone absorption
Use alternative antiemetic
Source: Kimi deep-research + Cla
Tetracycline
Moderate
Database
Reduced atovaquone plasma levels
Monitor; consider alternative
Source: Kimi deep-research + Cla
Warfarin
Moderate
Database
Proguanil potentiates anticoagulation
Monitor INR
Source: Kimi deep-research + Cla
Related guidelines
Ask House about Atovaquone + Proguanil
Continue into a citation-backed clinical answer with the drug context already attached.
Sources: Katzung·Verified: 2026-05-20 · House clinical team·Cockpit curated: 2026-05-20