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Pronunciation:

(a TOE va kwone)

U.S. Brand Names:

Mepron®

Generic Available:

Canadian Brand Names:

Mepron®

Use:

Acute oral treatment of mild to moderate Pneumocystis carinii pneumonia (PCP) in patients who are intolerant to co-trimoxazole; prophylaxis of PCP in patients intolerant to co-trimoxazole; treatment/suppression of Toxoplasma gondii encephalitis, primary prophylaxis of HIV-infected persons at high risk for developing Toxoplasma gondii encephalitis

Pregnancy Risk Factor:

Lactation:

Excretion in breast milk unknown/use caution

Contraindications:

Life-threatening allergic reaction to the drug or formulation

Warnings/Precautions:

Has only been indicated in mild to moderate PCP; use with caution in elderly patients due to potentially impaired renal, hepatic, and cardiac function

Adverse Reactions:

Note: Adverse reaction statistics have been compiled from studies including patients with advanced HIV disease; consequently, it is difficult to distinguish reactions attributed to atovaquone from those caused by the underlying disease or a combination, thereof.

>10%:

Central nervous system: Headache, fever, insomnia, anxiety

Dermatologic: Rash

Gastrointestinal: Nausea, diarrhea, vomiting

Respiratory: Cough

1% to 10%:

Central nervous system: Dizziness

Dermatologic: Pruritus

Endocrine & metabolic: Hypoglycemia, hyponatremia

Gastrointestinal: Abdominal pain, constipation, anorexia, dyspepsia, increased amylase

Hematologic: Anemia, neutropenia, leukopenia

Hepatic: Elevated liver enzymes

Neuromuscular & skeletal: Weakness

Renal: Elevated BUN/creatinine

Miscellaneous: Oral moniliasis

Drug Interactions:

Decreased effect: Rifamycins used concurrently decrease the steady-state plasma concentrations of atovaquone

Note: Possible increased toxicity with other highly protein-bound drugs

Ethanol/Nutrition/Herb Interactions:

Food: Ingestion with a fatty meal increases absorption.

Stability:

Do not freeze

Mechanism of Action:

Has not been fully elucidated; may inhibit electron transport in mitochondria inhibiting metabolic enzymes

Pharmacodynamics/Kinetics:

Absorption: Significantly increased with a high-fat meal

Distribution: 3.5 L/kg

Protein binding: >99%

Metabolism: Undergoes enterohepatic recirculation

Bioavailability: Tablet: 23%; Suspension: 47%

Half-life elimination: 2-3 days

Excretion: Feces (94% as unchanged drug)

Dosage:

Oral: Adolescents 13-16 years and Adults:

Prevention of PCP: 1500 mg once daily with food

Treatment of mild to moderate PCP: 750 mg twice daily with food for 21 days

Patient Education:

Take as directed. Take with high-fat meals. You may experience dizziness or lightheadedness; use caution when driving or engaging in tasks that require alertness until response to drug is known. Small meals may help reduce nausea. Report unresolved diarrhea, fever, mouth sores (use good mouth care), unresolved headache, or vomiting. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.

Dental Health: Effects on Dental Treatment:

Key adverse event(s) related to dental treatment: Oral moniliasis.

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

No information available to require special precautions

Mental Health: Effects on Mental Status:

May cause anxiety

Mental Health: Effects on Psychiatric Treatment:

May cause anemia and neutropenia; use caution with clozapine and carbamazepine

Dosage Forms:

Suspension, oral: 750 mg/5 mL (5 mL, 210 mL) [contains benzyl alcohol; citrus flavor]

International Brand Names:

Mepron® (CA); Wellvone® (AT, AU, BE, CH, DE, ES, FR, GB, IT, LU, NL, SE, ZA)

References

Artymowicz RJ and James VE, "Atovaquone: A New Antipneumocystis Agent,"Clin Pharm, 1993, 12(8):563-70.

El-Sadr WM, Murphy RL, Yurik TM, et al, "Atovaquone Compared With Dapsone for the Prevention of Pneumocystis carinii in Patients With HIV Infection Who Cannot Tolerate Trimethoprim, Sulfonamides, or Both,"N Engl J Med, 1998, 339(26):1889-95.

Haile LG and Flaherty JF, "Atovaquone: A Review,"Ann Pharmacother, 1993, 27(12):1488-94.

Hughes W, Leoung G, Kramer F, et al, "Comparison of Atovaquone (566C80) With Trimethoprim-Sulfamethoxazole to Treat Pneumocystis carinii Pneumonia in Patients With AIDS,"N Engl J Med, 1993, 328(21):1521-7.

Pagano G, Kennedy W, Weller S, et al, "The Safety and Pharmacokinetics of Atovaquone in Immunocompromised Children," Abstracts of the IX International Conference on AIDS in Affiliation With the IV STD World Congress: Berlin, 1993, June 6-11; Abs No PO-B10-1455.

Spencer CM and Goa KL, "Atovaquone. A Review of Its Pharmacological Properties and Therapeutic Efficacy in Opportunistic Infections,"Drugs, 1995, 50(1):176-96.

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