Atovaquone
Indications
Atovaquone is used for:
Malaria, Pneumocystis Carinii Pneumonia
Adult Dose
Oral
Malaria (P. falciparum)
1000 mg (with proguanil 400 mg) PO qDay x3 days
Pneumocystis Carinii Pneumonia
Treatment: 750 mg PO BID x21 days
Prophylaxis: 1500 mg/day PO, qDay or divided BID, with food
Child Dose
Malaria (P. Falciparum)
11-20 kg: 250 mg (with proguanil 100 mg)
21-30 kg: 500 mg (with proguanil 200 mg)
31-40 kg: 750 mg (with proguanil 300 mg)
All PO qDay x3 days
Renal Dose
Administration
Should be taken with food.
Contra Indications
History of hypersensitivity reactions (e.g., angioedema, bronchospasm, throat tightness, urticaria) to drug or components
Precautions
Oral absorption is limited but can be significantly increased when drug is taken with food; failure to administer with food may result in lower plasma concentrations and may limit response to therapy; consider therapy with other agents in patients who have difficulty taking oral suspension with food or in patients who have gastrointestinal disorders that may limit absorption of oral medications
Cases of cholestatic hepatitis, elevated liver enzymes, and fatal liver failure reported; if treating patients with severe hepatic impairment, closely monitor patients
Pregnancy-Lactation
Pregnancy Category: C
Lactation: excretion in milk unknown; use with caution
Interactions
Decreased plasma concentration w/ metoclopramide, tetracycline, rifamycin derivatives (e.g. rifampicin, rifabutin), efavirenz or boosted protease-inhibitors (e.g. ritonavir). Slightly decreased plasma concentration w/ aciclovir, antidiarrhoeals, benzodiazepines, cephalosporins, laxatives, opioids, paracetamol. May decrease the rate of metabolism and increase the plasma concentration of zidovudine. May decrease the trough and area under the curve concentration of indinavir. May increase the plasma concentration of etoposide. May displace other highly protein-bound drugs from plasma-protein binding sites.
Adverse Effects
Side effects of Atovaquone :
>10%
Abdominal pain (4-21%)
Cough (14-25%)
Depression (undefined)
Diarrhea (19-42%)
Dyspnea (15-21%)
Fever (14-40%)
Headache (16-31%)
Infection (18-22%)
Insomnia (10-19%)
Myalgia (undefined)
Nausea (21-32%)
Rash (22-46%)
Rhinitis (5-24%)
Vomiting (14-22%)
Weakness (8-31%)
1-10%
Amylase increased (7-8%)
Anemia (4-6%)
Anorexia (<7%)
Anxiety (<7%)
BUN/creatinine increased (<1%)
Constipation (<3%)
Dyspepsia (<5%)
Dizziness (3-8%)
Hyperglycemia (<9%)
Hypoglycemia (<1%)
Hyponatremia (7-10%)
Liver enzymes elevated (4-8%)
Neutropenia (3-5%)
Pruritus (5-10%)
Oral moniliasis (5-10%)
Taste perversion (<3%)
Mechanism of Action
Atovaquone, a hydroxynaphthoquinone, selectively inhibits the cytochrome bc1 complex (complex III) of the mitochondrial electron transport chain of a variety of protozoa and the parasitic fungus Pnuemocystitis jiroveci, resulting in the inhibition of nucleic acids and ATP synthesis. It is also used in combination w/ proguanil for the prevention and treatment of malaria caused by Plasmodium falciparum.