Atovaquone for Pneumocystis jirovecii Pneumonia and Malaria
Atovaquone is indicated for the treatment of mild-to-moderate Pneumocystis jirovecii pneumonia (PJP) and prevention of malaria, with specific dosing regimens for each condition. 1
Use in Pneumocystis jirovecii Pneumonia (PJP)
Indications
- Indicated for treatment of mild-to-moderate PJP in adults and adolescents (aged 13 years and older) who cannot tolerate trimethoprim-sulfamethoxazole (TMP-SMX) 1
- Recommended as an alternative agent for patients who are intolerant to TMP-SMX or who demonstrate clinical treatment failure after 5-7 days of TMP-SMX therapy 2
- Can be considered to complete a 21-day course in patients who show clinical improvement after 7-10 days of intravenous pentamidine therapy 2, 3
Dosage for PJP Treatment
- For adults and adolescents: 750 mg (5 mL) twice daily (total daily dose = 1,500 mg) administered with food for 21 days 1
- For children: 30-40 mg/kg/day in 2 divided doses given orally with fatty foods 2
- For infants aged 3-24 months: Higher dosage of 45 mg/kg/day may be required 2, 3
PJP Prophylaxis
- Recommended dosage for prevention: 1,500 mg (10 mL) once daily administered with food 1
- Atovaquone is an alternative for PJP prophylaxis in patients who cannot tolerate TMP-SMX 2, 4
Use in Malaria
Indications
- Atovaquone, typically combined with proguanil (as Atovaquone/proguanil), is effective for prevention and treatment of Plasmodium falciparum malaria, including drug-resistant strains 5
- Can be used as a second-line treatment for uncomplicated P. falciparum malaria when artemisinin-based combination therapies (ACTs) are contraindicated 2
Efficacy in Malaria
- Highly effective against drug-resistant strains of P. falciparum with prophylactic efficacy estimated at 95-100% 5
- Active against both hepatic (pre-erythrocytic) and erythrocytic stages of P. falciparum, providing both causal and suppressive prophylaxis 5
Important Administration Considerations
Food Requirements
- Must be administered with food, particularly food with high fat content, to enhance absorption 1, 6
- Food increases the bioavailability of atovaquone 1.4-fold over that achieved in the fasting state 2
- Failure to administer with food may result in lower plasma concentrations and limited therapeutic response 1
Drug Interactions
- Atovaquone concentration is increased with coadministration of fluconazole and prednisone 2, 3
- Concentration is decreased by coadministration with acyclovir, opiates, cephalosporins, rifampin, and benzodiazepines 2, 3
Adverse Effects
Common Adverse Reactions
- Most common adverse reactions include skin rashes (10-15%), nausea, and diarrhea 2, 3
- Most adverse reactions occur after the first week of therapy 2
- Elevated liver enzymes may be observed 2, 3
Safety Profile
- Generally well tolerated compared to alternative agents 5, 6
- Does not appear to cause bone marrow suppression, making it suitable for patients with hematologic disorders 6
- Cases of cholestatic hepatitis, elevated liver enzymes, and fatal liver failure have been reported, requiring close monitoring in patients with severe hepatic impairment 1
Clinical Considerations and Limitations
Efficacy Limitations
- Less effective than TMP-SMX for PJP treatment but has fewer treatment-limiting adverse effects 7
- Clinical experience for PJP treatment has been limited to mild-to-moderate cases (alveolar-arterial oxygen diffusion gradient [(A-a)DO₂] ≤45 mm Hg) 1
- Treatment of more severe PJP with atovaquone has not been well studied 1
- Efficacy in patients failing therapy with TMP-SMX has not been adequately studied 1
Special Populations
- Safe alternative for patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency who cannot receive TMP-SMX or dapsone 8
- Patients with diarrhea or gastrointestinal disorders may have limited absorption, potentially reducing efficacy 1, 7
Resistance Concerns
- When used as a single agent for malaria, resistance develops rapidly, necessitating combination therapy with proguanil 9
- Mutations in the parasite cytochrome bc₁ complex are responsible for atovaquone resistance in malaria 9
By following these evidence-based recommendations for atovaquone use in PJP and malaria, clinicians can optimize treatment outcomes while minimizing adverse effects in appropriate patient populations.