Atovaquone

Atovaquone, a hydroxynaphthoquinone, selectively inhibits the respiratory chain of protozoan mitochondria at the cytochrome bcl complex (complex III) by mimicking the natural substrate, ubiquinone. Inhibition of cytochrome bcl disrupts the mitochondrial electron transfer chain and leads to a breakdown of the mitochondrial membrane potential. Atovaquone is effective against all parasite stages in humans, including the liver stages. 

ACTs with amodiaquine, atovaquone-proguanil, chloroquine, clindamycin, doxycycline, lumefantrine,... 

Atovaquone 1 500 mg suspension by mouth once a day Elevated liver transaminases Nausea Rash... 

Chloroquine- Atovaquone- 250 mg atovaquone and 62.5 mg atovaquone Begin 1-2 days before departure... 

Atovaquone suspension 750 mg (5 mL) orally twice daily with meals for 21 days0 (Bl)... 

Rolan, P.E., Mercer, A.J., Weatherly, B.C., Holdich, T., Meire, H., Peck, R.W., Ridout, G. and Posner, J. (1994). Examination of some factors responsible for a food-induced increase in absorption of atovaquone. Br. J. Clin. Pharmacol. 37 13-20. 

Atoivastatin (Lipitor) Antihyperlipid-emic Tab 10, 20, 40 mg Atovaquone (Mepron) Antiprotozoal Susp 750 mg/5 ml... 

Hudson AT. (1993) Atovaquone — a novel broad-spectrum anti-infective drug. Parasitol Today 9 66-68. 

Drugs that might be affected by lopinavir/ritonavir include ergot derivatives, oral contraceptives, antiarrhythmics, HMG-CoA reductase inhibitors, HIV protease inhibitors, atovaquone, calcium channel blockers, ketoconazole, itraconazole, pimozide, cisapride, clarithromycin, disulfiram, metronidazole, immunosuppressants, midazolam, triazolam, narcotic analgesics, rifabutin and rifabutin metabolite, sildenafil, warfarin, bupropion, clozapine, desipramine, piroxicam, quinidine, theophylline, and zolpidem. 

Drugs that may affect zidovudine include acetaminophen, atovaquone, bone marrow suppressive/cytotoxic agents (eg, adriamycin, dapsone), clarithromycin, doxorubicin, fluconazole, ganciclovir, methadone, nelfinavir/ritonavir, phenytoin, probenecid, ribavirin, rifamycins, stavudine, trimethoprim, and valproic acid. 

Failure to administer with food may result in lower atovaquone plasma concentrations and may limit response to therapy. 

Pharmacology Atovaquone, an analog of ubiquinone, is an antiprotozoal with... 

Pharmacokinetics Absorption is enhanced approximately 2-fold when given with food. Atovaquone is extensively bound to plasma proteins (greater than 99.9%). 

CSF concentratons are less than 1% of plasma concentrations. Half-life ranged from 67 to 77.6 hours following the suspension. The long half-life is caused by presumed enterohepatic cycling and eventual fecal elimination. There is indirect evidence that atovaquone may undergo limited metabolism however, a specific metabolite has not been identified. 

Severe POP Clinical experience has been limited to patients with mild to moderate PCP. Treatment of more severe episodes of PCP has not been systematically studied. Atovaquone efficacy in patients who are failing therapy with TMP-SMZ has not been systematically studied. 

Lactation It is not known whether atovaquone is excreted into breast milk. 

Absorption Absorption of atovaquone is limited but can be significantly increased when the drug is taken with food. Plasma concentrations correlate with the likelihood of successful treatment and survival. Gl disorders may limit absorption of orally administered drugs. Patients with these disorders also may not achieve plasma concentrations of atovaquone associated with response to therapy in controlled trials. 

Concurrent puimonary conditions Atovaquone is not effective therapy for concurrent pulmonary conditions such as bacterial, viral, or fungal pneumonia or mycobacterial diseases. Clinical deterioration in patients may be due to infections with other pathogens, as well as progressive PCP. 

Use caution when administering atovaquone concurrently with other highly plasma protein bound drugs with narrow therapeutic indices as competition for binding sites may occur. 

Drug/Food interactions Administering atovaquone with food enhances its absorption by approximately 2-fold. 

Atovaquone (Mepron) [Antiprotozoal] Uses Rx prevention PCP Action 4- nucleic acid ATP synth Dose Rx 750 mg PO bid for 21 d Prevention 1500 mg PO once/d (w/ meals) Caution [C, ] Disp Susp SE FevCT, HA, anxiety, insomnia, rash, N/V Interactions X Effects W/ metoclopramide, rifabutin, rifampin, tetracycline EMS None OD Sxs unknown but may cause a rash symptomatic and supportive... 

Atovaquone is a hydroxy-1,4-naphthoquinone, an analog of ubiquinone, with antipneumocystic activity. Since 2000 atovaquone is available as a fixed dose preparation (Malarone) with proguanil for the oral treatment of falciperum malaria. Its activity probably is based on a selective inhibiton of mitochondrial electron transport with consequent inhibition of pyrimidin synthesis. Malarone should not be used to treat severe malaria, when an injectable drug is needed. 

For uncomplicated falciparum malaria there are several options (with the major drawback in brackets) halofantrine (arrhytmia), mefloquine (neurotoxicity), quinine (vomiting, tinnitus), artemether (recrudescence), atovaquone-proguanil (possible fast development of resistance). 

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