Atovaquone Treatment Regimen for Pneumocystis jirovecii Pneumonia
For the treatment of mild-to-moderate Pneumocystis jirovecii pneumonia (PCP), the recommended dosage of Mepron (atovaquone) is 750 mg (5 mL) twice daily with food for 21 days. 1
Dosing and Administration Guidelines
- Atovaquone oral suspension must be administered with food to ensure adequate absorption and therapeutic effect 1
- The total daily dose is 1,500 mg, divided into two 750 mg doses 1
- Treatment duration is 21 days for mild-to-moderate PCP 1
- Shake the suspension gently before administering the recommended dosage 1
Clinical Considerations for Atovaquone Use
- Atovaquone is indicated for mild-to-moderate PCP in adults and adolescents (aged 13 years and older) who cannot tolerate trimethoprim-sulfamethoxazole (TMP-SMX) 1
- Clinical experience with atovaquone for PCP treatment has been limited to patients with mild-to-moderate disease (alveolar-arterial oxygen diffusion gradient [(A-a)DO₂] ≤45 mm Hg) 1
- Atovaquone should not be used for severe PCP as its efficacy has not been established in this population 1, 2
- Failure to administer atovaquone with food may result in lower plasma concentrations and limited therapeutic response 1
Alternative Regimens and Special Populations
- For infants aged 3-24 months, a higher dosage of 45 mg/kg/day may be required if atovaquone is used 3
- For adults with clinical improvement after 7-10 days of intravenous pentamidine therapy, atovaquone may be considered to complete a 21-day course 3
- In patients with G6PD deficiency, atovaquone represents a safe alternative when TMP-SMX is contraindicated 4
Monitoring and Potential Adverse Effects
- Most common adverse reactions include skin rashes (10-15%), nausea, and diarrhea 3
- Elevated liver enzymes may occur, particularly after the first week of therapy 3
- Cases of cholestatic hepatitis, elevated liver enzymes, and fatal liver failure have been reported, requiring close monitoring in patients with severe hepatic impairment 1
- Drug interactions: Atovaquone concentration is increased with coadministration of fluconazole and prednisone, and decreased by coadministration with acyclovir, opiates, cephalosporins, rifampin, and benzodiazepines 3
Efficacy Considerations
- Atovaquone is slightly less effective than TMP-SMX for PCP treatment but has fewer treatment-limiting adverse effects 5
- In clinical trials, 20% of patients on atovaquone versus 7% on TMP-SMX did not respond to therapy 5
- Patients with diarrhea may have lower plasma drug concentrations, which is associated with therapeutic failure 5
- Therapeutic drug monitoring should be considered as more than half of immunocompromised patients have suboptimal atovaquone concentrations (Cmin <15 μg/mL) 6