Atovaquone

4-naphthoquinone, Hydroxy-1

Mechanism :

Atovaquone is a hydroxy-1,4-naphthoquinone, an analog of ubiquinone, with ant pneumocystis activity. The mechanism of action against P. carinii has not been fully elucidated.

Indication :

• Mild to moderate P. carinii pneumonia (PCP) in patients who are intolerant to trimethoprim-sulfamethoxazole (TMP-SMX)
• Babesiosis
• Prophylaxis in malaria

Contraindications :

Patients who develop, or have history of, potentially life-threatening allergic reactions to any of the components of the formulation.

Dosing :

Pneumocystis carinii, Babesiosis, Toxoplasmosis:

Treatment: 40 mg/kg/day BDS, max 1500 mg/day for 21 days. For toxoplasmosis give for

6 weeks. For babesiosis give along with azithromycin for 7-10 days.

Prophylaxis: 1-3 months and >2 years: 30 mg/kg/day, max 1500 mg/day, and for 4 months-2 years: 45 mg/kg/day, max 1500 mg/day.

Malaria (in combination with proguanil):

Each pediatric tablet contains 62.5 mg of atovaquone and 25 mg of proguanil.

Each adult tablet contains 250 mg of atovaquone and 100 mg of proguanil.

Prophylaxis of malaria:

<11 kg: Safety and efficacy not established.

11-20 kg: 62.5 mg/25 mg (1 pediatric tablet) PO daily.

21-30 kg: 125 mg/50 mg (2 pediatric tablets) PO daily.

31-40 kg: 187.5 mg/75 mg (3 pediatric tablets) PO daily.

>40 kg: 250 mg/100 mg (1 adult tablet) PO daily, beginning 1-2 days before travel to malaria-endemic area and continued until 7 days after return.

Treatment:

<5 kg: Safety and efficacy not established.

5-8 kg: 125 mg/50 mg (2 pediatric tablets) PO daily for 3 days.

9-10 kg: 187.5 mg/75 mg (3 pediatric tablets) PO daily for 3 days.

11-20 kg: 250 mg/100 mg (1 adult tablet) PO daily for 3 days.

21-30 kg: 500 mg/200 mg (2 adult tablets) PO daily for 3 days.

31-40 kg: 750 mg/300 mg (3 adult tablets) PO daily for 3 days.

>40 kg: 1 g/400 mg (4 adult tablets) PO daily for 3 days.

If the child vomits within an hour, repeat the dose.

Adverse Effect :

Fever, headache, insomnia, abdominal pain, diarrhea, nausea, dyspnea, methemoglobinemia, thrombocytopenia, keratopathy, pancreatitis, allergic reactions including erythema multiforme, acute renal impairment.

Interaction :

Plasma Protein Bound Drugs: Atovaquone is highly bound to plasma protein (>99.9%). Therefore, caution should be used when administering atovaquone concurrently with other highly plasma protein bound drugs with narrow therapeutic indices, as competition for binding sites may occur. The extent of plasma protein binding of atovaquone in human plasma is not affected by the presence of therapeutic concentrations of phenytoin, nor is the binding of this drug affected by the presence of atovaquone.
Rifampin: Coadministration of rifampin results in a significant decrease in average steady- state plasma atovaquone concentrations.
Rifabutin: Another rifamycin, is structurally like rifampin and may possibly have some of the same drug interactions as rifampin.

Renal Dose :

Hepatic Dose :