What are the common side effects of Mepron (atovaquone) in patients with HIV/AIDS?

Mepron (Atovaquone) Side Effects in HIV/AIDS Patients

The most common side effects of Mepron (atovaquone) are gastrointestinal disturbances—particularly diarrhea (19-42%), nausea (21-26%), and vomiting (14%)—along with rash (23-39%), which collectively affect the majority of patients but rarely require treatment discontinuation. 1

Most Frequent Adverse Reactions

Gastrointestinal Effects

• Diarrhea occurs in 19-42% of patients, making it the most common gastrointestinal side effect, though it leads to discontinuation in only 3-4% of cases 1
• Nausea affects 21-26% of patients and causes treatment discontinuation in approximately 3-4% 1
• Vomiting occurs in 14% of patients receiving atovaquone for PCP treatment 1

Dermatologic Reactions

• Rash develops in 23-39% of patients, with higher rates observed in prophylaxis trials (39-46%) compared to treatment trials (23%) 1
• Rash leads to discontinuation in approximately 6% of patients, though it is typically not severe 1
• The rash is generally maculopapular in nature 1

Other Common Side Effects (≥10% incidence)

• Headache affects 16-28% of patients 1
• Fever occurs in 14-25% 1
• Additional reactions include insomnia (10%), rhinitis (24%), pruritus, sweating, flu syndrome, sinusitis, depression, and myalgia 1

Serious but Less Common Adverse Reactions

Hepatotoxicity

• Cases of cholestatic hepatitis, elevated liver enzymes, and fatal liver failure have been reported, though the exact incidence is not well-defined 1
• In comparative trials, 2% of atovaquone-treated patients discontinued therapy due to ALT/AST elevations, compared to 7% with TMP-SMX 1
• Patients with severe hepatic impairment require close monitoring 1

Hypersensitivity Reactions

• Rare but serious hypersensitivity reactions can occur, including angioedema, bronchospasm, throat tightness, and urticaria 1
• These reactions contraindicate future use of atovaquone 1

Comparative Tolerability Profile

Versus TMP-SMX

• Atovaquone demonstrates superior tolerability compared to TMP-SMX, with only 9% of patients discontinuing atovaquone versus 24% discontinuing TMP-SMX due to adverse reactions 1
• Rash occurs less frequently with atovaquone (23%) than TMP-SMX (34%) 1
• However, gastrointestinal side effects (nausea, diarrhea, vomiting) are more common with atovaquone 1

Versus Pentamidine

• Atovaquone has markedly better tolerability than IV pentamidine, with only 7% discontinuation rate versus 41% for pentamidine 1
• Fewer patients receiving atovaquone reported adverse reactions overall (63% vs 72%) 1

Versus Dapsone

• Treatment discontinuation rates are similar between atovaquone (20%) and dapsone (43%) in prophylaxis settings among patients not previously taking either medication 1
• Gastrointestinal reactions are more common with atovaquone 1

Critical Clinical Considerations

Absorption-Related Issues

• Failure to take atovaquone with food significantly reduces absorption and may result in subtherapeutic drug levels, potentially limiting clinical response 1
• Food increases atovaquone bioavailability by 1.4-fold 2
• More than half (58%) of immunocompromised patients achieve plasma concentrations below the therapeutic threshold (Cmin <15 μg/mL), demonstrating unpredictable and highly variable absorption 3

Drug Interactions

• Atovaquone concentrations are decreased by concurrent use of rifampin, benzodiazepines, opiates, cephalosporins, and acyclovir 2
• Concentrations are increased by fluconazole and prednisone 2
• Atovaquone does not undergo significant CYP450 metabolism, avoiding many common antiretroviral drug interactions 4

Pediatric Considerations

• Adverse reactions appear less frequent in HIV-infected children (approximately 15%) compared to adults (40-65%) 2
• The most common pediatric adverse reactions are cutaneous (82% of reactions) followed by hematologic (18%) 2

Common Pitfalls to Avoid

• Never administer atovaquone without food—this is the single most important factor affecting therapeutic success, as inadequate absorption leads to treatment failure 1
• Do not use atovaquone in patients with severe gastrointestinal disorders that limit oral medication absorption; consider alternative agents 1
• Monitor liver function in patients with pre-existing hepatic impairment given reports of hepatotoxicity 1
• Recognize that most adverse reactions occur after the first week of therapy 2