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Pronunciation
(a TOE va kwone)
Generic Available (U.S.)
No
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Acute oral treatment of mild-to-moderate Pneumocystis jirovecii pneumonia (PCP) in patients who are intolerant to co-trimoxazole; prophylaxis of PCP in patients who are intolerant to co-trimoxazole
Use: Unlabeled
Treatment of babesiosis; treatment/suppression of Toxoplasma gondii encephalitis; primary prophylaxis of HIV-infected persons at high risk for developing Toxoplasma gondii encephalitis
Pregnancy Risk Factor
C
Pregnancy Considerations
There are no adequate and well-controlled studies of atovaquone in pregnant women. Use in pregnant women only if the potential benefit outweighs the possible risk to the fetus.
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Life-threatening allergic reaction to atovaquone or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• Diarrhea/vomiting: Absorption may be decreased in patients who have diarrhea or vomiting; monitor closely and consider use of an antiemetic. If severe, consider use of an alternative antimalarial.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with severe hepatic impairment; rare cases of hepatitis, elevated liver function tests, and liver failure have been reported.
• Pneumocystis jirovecii pneumonia (PCP): Appropriate use: When used for treatment, has only been indicated in mild-to-moderate PCP; not studied for use in severe PCP.
Special populations:
• Elderly: 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: Fever (14% to 40%), headache (16% to 31%), insomnia (10% to 19%), depression, pain
Dermatologic: Rash (22% to 46%), pruritus (5% to ≥10%)
Gastrointestinal: Diarrhea (19% to 42%), nausea (21% to 32%), vomiting (14% to 22%), abdominal pain (4% to 21%)
Neuromuscular & skeletal: Weakness (8% to 31%), myalgia
Respiratory: Cough (14% to 25%), rhinitis (5% to 24%), dyspnea (15% to 21%), sinusitis (7% to ≥10%)
Miscellaneous: Infection (18% to 22%), diaphoresis, flu-like syndrome
1% to 10%:
Cardiovascular: Hypotension (≤1%)
Central nervous system: Dizziness (3% to 8%), anxiety (≤7%)
Endocrine & metabolic: Hyponatremia (7% to 10%), hyperglycemia (≤9%), hypoglycemia (≤1%)
Gastrointestinal: Amylase increased (7% to 8%), anorexia (≤7%), dyspepsia (≤5%), constipation (≤3%), taste perversion (≤3%)
Hematologic: Anemia (4% to 6%), neutropenia (3% to 5%)
Hepatic: Liver enzymes increased (4% to 8%)
Renal: BUN increased (≤1%), creatinine increased (≤1%)
Respiratory: Bronchospasm (2% to 4%)
Miscellaneous: Oral moniliasis (5% to 10%)
Postmarketing and/or case reports: Acute renal failure, allergic reaction, angioedema, erythema multiforme, hepatitis (rare), hypersensitivity reactions, liver failure (rare), methemoglobinemia, pancreatitis, skin desquamation, Stevens-Johnson syndrome, throat tightness, thrombocytopenia, urticaria, vortex keratopathy
Metabolism/Transport Effects
None known.
Drug Interactions
Etoposide: Atovaquone may increase the serum concentration of Etoposide. Management: Separate administration of atovaquone and etoposide by at least 1-2 days. Avoid concomitant administration of atovaquone and etoposide. Risk D: Consider therapy modification
Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemic Agents. Risk C: Monitor therapy
Hypoglycemic Agents: May enhance the adverse/toxic effect of other Hypoglycemic Agents. Risk C: Monitor therapy
Indinavir: Atovaquone may decrease the serum concentration of Indinavir. Risk C: Monitor therapy
Rifamycin Derivatives: May decrease the serum concentration of Atovaquone. Risk D: Consider therapy modification
Ritonavir: May decrease the serum concentration of Atovaquone. Risk C: Monitor therapy
Tetracycline: May decrease the serum concentration of Atovaquone. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Food: Ingestion with a fatty meal increases absorption. Management: Administer with food, preferably high-fat meals (peanuts or ice cream).
Herb/Nutraceutical: Herbs with hypoglycemic properties may enhance the hypoglycemic effect of atovaquone. Management: Avoid alfalfa, aloe, bilberry, bitter melon, burdock, celery, damiana, fenugreek, garcinia, garlic, ginger, ginseng (American), gymnema, marshmallow, and stinging nettle.
Storage
Store at 15°C to 25°C (59°F to 77°F). Do not freeze.
Mechanism of Action
Inhibits electron transport in mitochondria resulting in the inhibition of key metabolic enzymes responsible for the synthesis of nucleic acids and ATP
Pharmacodynamics/Kinetics
Absorption: Significantly increased with a high-fat meal
Distribution: Vdss: 0.6 ± 0.17 L/kg
Protein binding: >99%
Metabolism: Undergoes enterohepatic recirculation
Bioavailability: 32% to 62%
Half-life elimination: 1.5-4 days
Excretion: Feces (>94% as unchanged drug); urine (<1%)
Dosage
Oral:
Children <13 years (unlabeled uses):
Prevention of PCP (CDC, 2009):
1-3 months: 30 mg/kg once daily with food
4-24 months: 45 mg/kg once daily with food
>24 months: 30 mg/kg once daily with food
Treatment of mild-to-moderate PCP (CDC, 2009):
Birth to 3 months: 30-40 mg/kg/day in 2 divided doses with food (maximum: 1500 mg/day)
3-24 months: 45 mg/kg/day in 2 divided doses with food (maximum: 1500 mg/day)
≥24 months: 30-40 mg/kg/day in 2 divided doses with food (maximum: 1500 mg/day)
Toxoplasma gondii prophylaxis (CDC, 2009):
1-3 months: 30 mg/kg once daily with food
4-24 months: 45 mg/kg once daily with food
>24 months: 30 mg/kg once daily with food
Babesiosis: 40 mg/kg/day in 2 divided doses with food for 7-10 days
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
Toxoplasma gondii encephalitis (unlabeled use; AIDSinfo guidelines):
Prophylaxis: 1500 mg once daily with food
Treatment: 750 mg 4 times daily or 1500 mg twice daily with food for at least 6 weeks after resolution of signs and symptoms
Suppression after treatment: 750 mg 2-4 times/day with food
Babesiosis (unlabeled use): 750 mg twice daily with azithromycin for 7-10 days
Administration: Oral
Must be taken administered meals. Shake suspension gently before use. Once opened, the foil pouch can be emptied on a dosing spoon, in a cup, or directly into the mouth.
Dietary Considerations
Must be taken with meals.
Patient Education
Take with high-fat meals. You may experience dizziness or lightheadedness, problems sleeping, rash, weakness, cough, or flu-like symptoms. Report unresolved diarrhea, fever, mouth sores, unresolved headache, abdominal pain, shortness of breath, or vomiting.
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
Nursing: Physical Assessment/Monitoring
Monitor for CNS and respiratory changes.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, oral:
Mepron®: 750 mg/5 mL (5 mL, 210 mL) [contains benzyl alcohol; citrus flavor]
Pricing: U.S. (www.drugstore.com)
Suspension (Mepron)
750 mg/5 mL (210): $1124.69
References
Artymowicz RJ and James VE, “Atovaquone: A New Antipneumocystis Agent,” Clin Pharm, 1993, 12(8):563-70.
Behbahani R, Moshfeghi M, and Baxter JD, “Therapeutic Approaches for AIDS-Related Toxoplasmosis,” Ann Pharmacother, 1995, 29(7-8):760-8.
Centers for Disease Control and Prevention, “Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV-Exposed and HIV-Infected Children: Recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics,” MMWR Recomm Rep, 2009, 58(RR-11):1-166. Available at http://aidsinfo.nih.gov/contentfiles/Pediatric_OI.pdf
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.
“Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-infected Adults and Adolescents. Panel on Clinical Practices for Treatment of HIV Infection,” June 18, 2008. Available at http://www.aidsinfo.nih.gov
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.
Katlama C, Mouthon B, Gourdon D, et al, “Atovaquone as Long-term Suppressive Therapy for Toxoplasmic Encephalitis in Patients With AIDS and Multiple Drug Intolerance. Atovaquone Expanded Access Group,” AIDS, 1996, 10(10):1107-12.
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.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
Content last modified March 2012
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