What is the recommended dosage and treatment duration of Atovaquone (generic name) for Pneumocystis pneumonia (PCP) treatment?

Atovaquone for PCP Treatment

For mild-to-moderate PCP, atovaquone should be dosed at 750 mg (5 mL) orally twice daily with food for 21 days in adults and adolescents aged ≥13 years, or 30-40 mg/kg/day divided into 2 doses with fatty foods in children (with infants 3-24 months requiring 45 mg/kg/day). 1, 2

Indication and Patient Selection

Atovaquone is recommended as an alternative agent for mild-to-moderate PCP only, not as first-line therapy 2, 1:

• Use when patients cannot tolerate TMP-SMX (the first-line agent) 1
• Appropriate for PCP with PaO₂ ≥70 mmHg or alveolar-arterial oxygen gradient <45 mmHg 3
• Not recommended for severe PCP (A-a gradient >45 mmHg), as efficacy has not been established in this population 1
• Evidence strength is BI for adults, but data are limited for children 2

Dosing Regimens

Adults and Adolescents (≥13 years)

• Treatment dose: 750 mg (5 mL) twice daily with food for 21 days 1
• Prevention dose: 1,500 mg (10 mL) once daily with food 1

Pediatric Patients

• Children: 30-40 mg/kg/day divided into 2 doses, administered with fatty foods 2
• Infants 3-24 months: Higher dose of 45 mg/kg/day required due to different pharmacokinetics 2, 4

Sequential Therapy Option

• After 7-10 days of IV pentamidine with clinical improvement, atovaquone may be considered to complete the 21-day treatment course 2

Critical Administration Requirements

Atovaquone MUST be administered with food—this is non-negotiable 1, 4:

• Food increases bioavailability 1.4-fold compared to fasting state 2, 4
• Fatty foods are preferred for optimal absorption 2
• Failure to give with food results in suboptimal plasma concentrations and treatment failure 1, 4
• Shake the suspension gently before each dose 1

Patients Who Should NOT Receive Atovaquone

• Those with severe malabsorption or chronic diarrhea (unreliable absorption) 1, 4
• Patients unable to take oral medications with food consistently 4
• Those with severe PCP requiring more aggressive therapy 1
• Patients with known serious hypersensitivity reactions to atovaquone 1

Drug Interactions

Medications That DECREASE Atovaquone Levels (Avoid or Monitor Closely)

• Rifampin and rifabutin: Concomitant use NOT recommended 1, 2, 4
• Tetracycline: Use caution; monitor for loss of efficacy 1
• Metoclopramide: Use only if other antiemetics unavailable 1
• Other agents: acyclovir, opiates, cephalosporins, benzodiazepines 2, 4

Medications That INCREASE Atovaquone Levels

• Fluconazole and prednisone increase concentrations 2, 4

Medications Affected BY Atovaquone

• Indinavir: Atovaquone reduces indinavir trough concentrations; monitor for loss of HIV control 1

Adverse Effects

Common adverse reactions (occurring in 10-25% of patients) 2:

• Rash (10-15%), including maculopapular rash
• Nausea and diarrhea
• Headache
• Fever
• Elevated liver enzymes

Hepatotoxicity warning: Cases of hepatitis and fatal liver failure have been reported 1

Most adverse reactions occur after the first week of therapy 2

Clinical Efficacy Data

In the large Treatment IND study of 940 HIV-positive patients 5:

• Mild-to-moderate PCP: 78% clinical response rate (591/760 patients)
• Severe PCP: Only 56% response rate (79/140 patients), with 38% mortality
• 23% discontinued treatment prematurely in mild-to-moderate cases

Atovaquone was slightly less effective than TMP-SMX but better tolerated, with fewer treatment-limiting adverse reactions 6

Common Pitfalls to Avoid

1. Not administering with food: This is the most common error leading to treatment failure 1, 4
2. Using for severe PCP: Atovaquone has not been adequately studied and should not be used when A-a gradient >45 mmHg 1
3. Combining with rifampin: This significantly reduces atovaquone levels and should be avoided 1
4. Ignoring malabsorption: Patients with GI disorders may have suboptimal drug levels 1, 4
5. Underdosing infants: Remember that infants 3-24 months require the higher 45 mg/kg/day dose 2, 4

Alternative Agents When Atovaquone Cannot Be Used

For patients who cannot reliably take medication with food or have malabsorption, consider 4:

• Dapsone-based regimens
• Aerosolized pentamidine (for prophylaxis only)
• TMP-SMX desensitization if feasible

For severe PCP when TMP-SMX cannot be used, clindamycin plus primaquine is preferred over atovaquone 4, 3