Sulfadiazine

Drug class: sulfonamide antibiotic

Indications: treatment and prophylaxis of cerebral toxoplasmosis, only in combination with pyrimethamine.

Dose: For treatment 2-3 500 mg tablets qid (daily dose 4-6 g). For prophylaxis halve the dose (500 mg qid)!

Renal insufficiency: creatinine clearance 50-10 ml/min: halve dose. At values below 10 ml/min: administer one third of the dose.

Side effects: very frequently, allergies with pruritus, fever and urticaria, often treatment-limiting. Rare: Stevens-Johnson syndrome. Gastrointestinal complaints such as nausea, vomiting, diarrhea. Renal problems with renal failure, crystalluria, nephrolithiasis in up to 7 %. Anemia, leukopenia, thrombocytopenia. Elevated liver enzymes.

Comments/Warnings: sulfadiazine is contraindicated in sulfonamide hypersensitivity and allergies to sulfonylurea antidiabetics, acetazolamide or thiazide diuretics; also in G6PD deficiency, renal failure and severe hepatic disease or dysfunction (e.g. acute hepatitis); and during pregnancy and breastfeeding.

Sulfadiazine can increase levels of sulfonyl urea (oral antidiabetics), anticoagulants, diphenylhydantoin.

Concurrent dosing with antacids reduces absorption of sulfadiazine (separate administration 1-2 hours apart). Ensure sufficient intake of fluids (at least 2 l daily). Monitor blood count, ALT, creatinine, and BUN at least weekly initially. Monitor urine! In case of crystalluria: alkalize urine. References:

1. Caumes E, Bocquet H, Guermonprez G, et al. Adverse cutaneous reactions to pyrimethamine/sulfadiazine and pyrimethamine/clindamycin in patients with AIDS and toxoplasmic encephalitis. Clin Infect Dis 1995, 21: 656-8. http://amedeo.com/lit.php?id=8527561

2. Chirgwin K, Hafner R, Leport C, et al. Randomized phase II trial of atovaquone with pyrimethamine or sulfadiazine for treatment of toxoplasmic encephalitis in patients with acquired immunodeficiency syndrome: ACTG 237/ANRS 039 Study. Clin Infect Dis 2002, 34: 1243-50. http://amedeo.com/lit.php?id=11941551

3. Dannemann B, McCutchan JA, Israelski D, et al. Treatment of toxoplasmic encephalitis in patients with AIDS. A randomized trial comparing pyrimethamine plus clindamycin to pyrimethamine plus sulfadiazine. Ann Intern Med 1992, 116: 33-43. http://amedeo.com/lit.php?id=1727093

4. Katlama C, De Wit S, O'Doherty E, et al. Pyrimethamine-clindamycin vs. pyrimethamine-sulfadiazine as acute and long-term therapy for toxoplasmic encephalitis in patients with AIDS. Clin Infect Dis 1996, 22: 268-75. http://amedeo.com/lit.php?id=8838183

5. Molina JM, Belenfant X, Doco-Lecompte T, et al. Sulfadiazine-induced crystalluria in AIDS patients with toxoplasma encephalitis. AIDS 1991, 5: 587-9. http://amedeo.com/lit.php?id=1863412

6. Podzamczer D, Miro JM, Bolao F, et al. Twice-weekly maintenance therapy with sulfadiazine-pyrimethamine to prevent recurrent toxoplasmic encephalitis in patients with AIDS. Ann Intern Med 1995, 123: 175-80. http://amedeo.com/lit.php?id=7598298

T-20 (Enfuvirtide) 757

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