MEPRON
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MEPRON (MEPRON).
It is a hydroxynaphthoquinone that selectively inhibits mitochondrial electron transport chain in Plasmodium species, specifically at the cytochrome bc1 complex (Complex III), leading to collapse of mitochondrial membrane potential and inhibition of pyrimidine synthesis.
| Metabolism | Hepatic metabolism; primarily glucuronidation (UGT1A1, UGT1A9). Not significantly metabolized by CYP450 enzymes. |
| Excretion | Primarily fecal (87-94%) via bile; renal excretion accounts for <1% as unchanged drug. A minor metabolite, atovaquone glucuronide, is excreted in urine. |
| Half-life | Mean terminal elimination half-life is 2.2-3.2 days (approximately 53-77 hours) in adults; prolonged in hepatic impairment (up to 22 days) and in elderly (up to 5 days). |
| Protein binding | Highly protein bound (>99.9%), primarily to albumin. |
| Volume of Distribution | 0.5-0.8 L/kg, indicating extensive tissue distribution (total body water). High Vd reflects penetration into tissues, including lungs and brain. |
| Bioavailability | Oral bioavailability is variable (23-47%) and highly dependent on food; absorption increases 2-fold or more when administered with a high-fat meal. |
| Onset of Action | Oral: clinical response typically observed within 3-5 days for pneumocystis pneumonia treatment. Prophylactic effect requires 1-2 weeks of dosing. |
| Duration of Action | Duration of therapeutic effect persists for the dosing interval (daily for treatment; every 24-72 hours for prophylaxis). Continued therapy required for full treatment course to prevent relapse. |
750 mg orally twice daily with food for 21 days for treatment of mild-to-moderate Pneumocystis jirovecii pneumonia. For prophylaxis: 1500 mg orally once daily with food.
| Dosage form | SUSPENSION |
| Renal impairment | For CrCl < 30 mL/min: no dose adjustment required; monitor closely. No data for hemodialysis or peritoneal dialysis. |
| Liver impairment | No specific guidelines; use with caution in severe hepatic impairment. Child-Pugh classification not formally evaluated. |
| Pediatric use | Children ≥ 13 years: same as adult. Children 1-4 months: 30 mg/kg/day orally divided twice daily; 5-23 months: 45 mg/kg/day divided twice daily; 2-12 years: 30 mg/kg/day divided twice daily; all for treatment. Prophylaxis: ≥ 13 years: 1500 mg once daily; < 13 years: 30 mg/kg once daily (max 1500 mg). |
| Geriatric use | No specific dose adjustment; consider renal function and potential for increased adverse effects. Use with caution due to limited data. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MEPRON (MEPRON).
| Breastfeeding | Not recommended for nursing women. Atovaquone is excreted in human milk; M/P ratio is unknown. Potential for serious adverse reactions in nursing infants. Decision to discontinue nursing or drug should consider importance of drug to mother. |
| Teratogenic Risk | FDA Pregnancy Category B. Animal studies at up to 4 times the human dose (based on AUC) showed no evidence of teratogenicity. No adequate, well-controlled studies in pregnant women. Risk of fetal harm cannot be ruled out; use only if clearly needed. No known risk of major malformations, miscarriage, or adverse fetal outcomes specifically attributed to atovaquone in human reports. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to atovaquone or any component of the formulation.
| Precautions | Use with caution in patients with hepatic or renal impairment; may cause hypoglycemia; monitor for hypersensitivity reactions including Stevens-Johnson syndrome; potential for drug interactions with rifampin, rifabutin, and tetracycline (reduces atovaquone levels). |
Loading safety data…
| Fetal Monitoring | No specific maternal or fetal monitoring required beyond standard obstetrical care. Monitor for maternal adverse effects (rash, hepatitis, pancreatitis) and potential signs of treatment failure. |
| Fertility Effects | No studies on fertility in humans. In animal studies, atovaquone did not impair fertility in rats at exposures up to 4 times human clinical exposure based on AUC. No known effect on human fertility. |