Atovaquone adverse effects

Atovaquone is an alternative therapy for P jiroveci infection, although its efficacy is lower than that of trimethoprim-sulfamethoxazole. Standard dosing is 750 mg taken with food twice daily for 21 days. Adverse effects include fever, rash, nausea, vomiting, diarrhea, headache, and insomnia. Serious adverse effects appear to be minimal, although experience with the drug remains limited. Atovaquone has also been effective in small numbers of immunocompromised patients with toxoplasmosis unresponsive to other agents, although its role in this disease is not yet defined. 

Malarone is generally well tolerated. Adverse effects include abdominal pain, nausea, vomiting, diarrhea, headache, and rash, and these are more common with the higher dosage required for treatment. Reversible elevations in liver enzymes have been reported. The safety of atovaquone in pregnancy is unknown. Plasma concentrations of atovaquone are decreased about 50% by co-administration of tetracycline or rifampin. 

Adverse Effects. Atovaquone may cause side effects such as fever, skin rash, cough, headache, and gastrointestinal problems (nausea, vomiting, diarrhea). 

ATOVAQUONE H2 RECEPTOR BLOCKERS - CIMETIDINE t efficacy and adverse effects of antimalarials Inhibition of metabolism, some definitely via CYP3A4 Avoid co-administration... 

Two other agents show promise in treatment of ocular toxoplasmosis. Atovaquone, primarily used for mild to moderate episodes of Pneumocystis carinii pneumonia, has been effective in small series of patients with toxoplasmosis. It appears to have activity against both tachy-zoites and tissue cysts. More recent studies on atovaquone in toxoplasmosis are limited to murine models, and no further reports on this drug therapy in humans have been published. Azithromycin, a macrolide antibiotic, is efficacious against T. gondii and can also kill tissue cysts. A randomized study of 46 patients compared the combinations of azithromycin plus pyrimethamine versus pyrimethamine plus sulfadiazine in treatment of ocular toxoplasmosis efficacy was similar, but the azithromycin/ pyrimethamine regimen caused less adverse effects. 

Of 39 patients who had bone marrow transplants and who were randomized to receive either co-trimoxazole or atovaquone as prophylaxis in an open-label trial, eight taking co-trimoxazole withdrew because of presumed drug reactions, although in five of these the reported neutropenia and thrombocytopenia could have been a consequence of transplantation itself or of other drugs (2). None of 16 patients treated with atovaquone withdrew. This rate of reported adverse effects with co-trimoxazole is higher than usually reported in clinical practice with prophylactic dosages. 

When atovaquone was compared with intravenous pentamidine in the treatment of mild and moderate Pneumocystis jiroveci pneumonia in an open trial, the success rates were similar. However, withdrawal of the original treatment was much more frequent with pentamidine (36%) than atovaquone (4%) (4). However, the authors conclusion that the two approaches have a similar success rate has been challenged, and their series was small (5,6). Treatment-limited adverse effects occurred in only 7% of patients given atovaquone, compared with 41 % given pentamidine. They included cases of rash and an increase in creatinine concentrations atovaquone (unlike pentamidine) produced no vomiting, nausea, hypotension, leukopenia, acute renal insufficiency, or electrocardiographic abnormalities, but it did cause one case of dementia (4). 

Atovaquone acts synergistically with proguanil, and the combination of these two drugs (Malarone ) is highly efficacious in the treatment of uncomplicated malaria (8), including that against multidrug resistant forms, and in prophylaxis (9). It has not yet been widely marketed, so data on rare adverse effects are currently sparse. 

An inpatient study of 79 patients given proguanil + atovaquone compared with 79 patients given mefloquine showed no malaria-independent adverse effects (10). Although there was a significant transient increase in liver enzymes, this was probably of limited clinical importance. 

In a prospective, open, randomized trial clindamycin (600 mg tds) and quinine (650 mg tds) were compared with atovaquone (750 mg bd) plus azithromycin (500 mg on day 1 followed by 250 mg/day) in 58 patients with non-life-threatening babesiosis (3). Bacterial response was complete 3 months after the end of treatment. Adverse effects were reported by 72% of those who received clindamycin and quinine compared with 15% of those who received atovaquone and azithromycin. The most common adverse effects with clindamycin and quinine were tinnitus (39%), diarrhea (33%), and impaired hearing (28%) the symptoms had resolved in 73% of the patients assigned to clindamycin/quinine 3 months after the start of therapy and in 100% after 6 months. 

Clinical use and toxicity Atovaquone is approved for use in mild to moderate pneumo-cystis pneumonia. It is less effective than TMP-SMZ or pentamidine, but is better tolerated. Adverse effects include rash, cough, nausea, vomiting, diarrhea, fever, and abnormal Uver function tests. 

Moderate increases in the AUC of zidovudine, not usually requiring dose adjustments, have been seen with atovaquone. However, it may be prudent to regularly monitor for adverse effects. Atovaquone decreased the AUC of didanosine. Neither didanosine nor zidovudine affected atovaquone pharmacokinetics. 

The manufacturer of atovaquone notes that the decrease in didanosine levels is unlikely to be clinically relevant. They also say that the increased plasma levels of zidovudine likely with a 3-week course of atovaquone for acute Pneumocystis pneumonia are unlikely to increase the adverse effects of zidovudine, and routine dose adjustments are not required. Nevertheless, the manufacturers of atovaquone and zidovudine do recommend reg-... 

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