Atovaquone
Synonyms :
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.
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 :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | Dose as in normal renal function |
| <10 | Dose as in normal renal function |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Not dialysed. Dose as in normal renal function |
| HD | Not dialysed. Dose as in normal renal function |
| HDF/High flux | Unknown dialysability. Dose as in normal renal function |
| CAV/VVHD | Unlikely to be dialysed. Dose as in normal renal function |
Hepatic Dose :
Mild to moderate hepatic impairment: No dose adjustment required.
Severe hepatic impairment: Studies have not been conducted in these patients.