Treatment of chloroquine-resistant falciparum malaria—Fansidar is no longer a recommended therapy for malaria, and in particular it should not be used for severe malaria, since it is slower-acting than other available agents. Fansidar is also not reliably effective in vivax malaria, and its usefulness against P ovale and P malariae has not been adequately studied. Artesunate plus sulfadoxine-pyrimethamine is listed by the WHO to treat falciparum malaria (Table 52–4), but other artemisininbased combinations are generally preferred.
4.
Toxoplasmosis—Pyrimethamine, in combination with sulfadiazine, is first-line therapy in the treatment of toxoplasmosis, including acute infection, congenital infection, and disease in immunocompromised patients. For immunocompromised patients, high-dose therapy is required followed by chronic suppressive therapy. Folinic acid is included to limit myelosuppression. The replacement of sulfadiazine with clindamycin provides an effective alternative regimen. Recent problems with pricing and availability of pyrimethamine in the USA made the use of this drug more difficult.
5.
Pneumocystosis—P jiroveci is the cause of human pneumocystosis and is now recognized to be a fungus, but this organism is discussed in this chapter because it responds to antiprotozoal drugs, not antifungals. First-line therapy of pneumocystosis is trimethoprim plus sulfamethoxazole (see also Chapter 46). Standard treatment includes high-dose intravenous or oral therapy (15 mg/kg trimethoprim and 75 mg/kg sulfamethoxazole per day in three or four divided doses) for 21 days. High-dose therapy entails significant toxicity, especially in patients with AIDS. Important toxicities include nausea, vomiting, fever, rash, leukopenia, hyponatremia, elevated hepatic enzymes, azotemia, anemia, and thrombocytopenia. Less common effects include severe skin reactions, mental status changes, pancreatitis, and hypocalcemia. Trimethoprim-sulfamethoxazole is also the standard chemoprophylactic drug for the prevention of P jiroveci infection in immunocompromised individuals. Dosing is one double-strength tablet daily or three times per week. The chemoprophylactic dosing schedule is much better tolerated than high-dose therapy, but rash, fever, leukopenia, or hepatitis may necessitate changing to another drug.
Most patients tolerate pyrimethamine and proguanil well. Gastrointestinal symptoms, skin rashes, and itching are rare. Mouth ulcers and alopecia have been described with proguanil. Fansidar uncommonly causes severe cutaneous reactions, including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Severe reactions appear to be much less common with single-dose or intermittent therapy, compared to regular chemoprophylaxis, and use of the drug has been justified by the risks associated with falciparum malaria.
Rare adverse effects with Fansidar are those associated with other sulfonamides, including hematologic, gastrointestinal, central nervous system, dermatologic, and renal toxicity. Folate antagonists should be used cautiously in the presence of renal or hepatic dysfunction. Although pyrimethamine is teratogenic in animals, Fansidar has been safely used in pregnancy. Proguanil is considered safe in pregnancy. In pregnant women receiving Fansidar preventive therapy, high-dose folate supplementation (eg, 5 mg daily) should be replaced by the standard recommended dosage (0.4–0.6 mg daily) to avoid potential loss of protective efficacy.