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Pyrimethamine is authorised in the world under the following brand names: Darachlor, Daraclor, Darapram, Daraprim, Daraprime, Disulone, Erbaprelina, Fansidar, Khloridin, Malacid, Malocid, Malocide, Maloprim, Pirimecidan, Tindurin, Tinduring.
• Sulfadiazine is an intermediate-acting antibacterial sulfonamide.
Sulfadiazine shares the actions and uses of the other anti-infective sulfonamides.
Dosage and Administration
Sulfadiazine is administered orally. Patients should be instructed to drink one full glass (250 mL) of water with each dose of the drug and at frequent intervals throughout the day while they are receiving sulfadiazine.
The usual adult dosage of sulfadiazine is 2-4 g initially, followed by 2-4 g daily administered in 3-6 equally divided doses. Children older than 2 months of age may receive 75 mg/kg or 2 g/m2 initially, followed by 150 mg/kg or 4 g/m2 daily administered in 4-6 equally divided doses. Total daily pediatric dosage should not exceed 6 g.
For continuous prophylaxis of recurrent rheumatic fever (secondary prevention), the usual dosage of sulfadiazine for patients weighing less than 30 kg is 500 mg once daily; patients weighing more than 30 kg may receive 1 g once daily. Sulfadiazine should not be used for the treatment of Streptococcus pyogenes (group A b-hemolytic streptococci) infections.
For the treatment of nocardiosis, some clinicians recommend that 4-8 g of sulfadiazine be given daily for a minimum of 6 weeks. Sulfonamide therapy is often continued for many months after apparent cure of nocardiosis to prevent relapse of the infection.
Asymptomatic Meningococcal Carriers
For the treatment of meningococcal carriers and prophylaxis of meningococcal disease when the organism is known to be susceptible to sulfonamides, adults should receive 1 g of sulfadiazine twice daily for 2 days, children 1-12 years of age should receive 500 mg twice daily for 2 days, and children 2-12 months of age should receive 500 mg once daily for 2 days.
Pyrimethamine in conjunction with sulfadiazine is the treatment of choice for toxoplasmosis in adults and children, including toxoplasmosis in immunocompromised individuals (e.g., those with acquired immunodeficiency syndrome [AIDS]).
When sulfadiazine is used in combination with pyrimethamine for the treatment of toxoplasmosis, the usual adult dosage of sulfadiazine is 1-1.5 g 4 times daily and the usual pediatric dosage is 100-200 mg/kg daily. The optimum duration of therapy has not been established, but treatment usually is continued for 3-4 weeks. The AAP states the optimal dosage and duration of therapy in neonates with congenital toxoplasmosis have not been determined and consultation with an expert is recommended, but that therapy should be prolonged and often is 1 year.
For long-term suppressive or maintenance therapy (secondary prophylaxis) to prevent relapse of toxoplasmosis in patients with human immunodeficiency virus (HIV) infection, the Prevention of Opportunistic Infections Working Group of the US Public Health Service and the Infectious Diseases Society of America (USPHS/IDSA) recommends that adults and adolescents receive oral sulfadiazine in a dosage of 0.5-1 g every 6 hours with oral pyrimethamine (25-50 mg daily) and oral leucovorin (10-25 mg once daily). For long-term suppressive therapy of toxoplasmosis in HIV-infected infants and children, the USPHS/IDSA recommends an oral sulfadiazine dosage of 85-120 mg/kg daily given in 2-4 divided doses with oral pyrimethamine (1 mg/kg or 15 mg/m2 daily [maximum dose 25 mg]) and oral leucovorin (5 mg once every 3 days).
Sulfadiazine shares the toxic potentials of the sulfonamides, and the usual precautions of sulfonamide therapy should be observed, including maintenance of adequate fluid intake to reduce the risk of crystalluria.
Sulfadiazine is readily absorbed from the GI tract. After oral administration of a single 2-g dose of sulfadiazine, peak plasma concentrations of 60 mcg/mL were reached within 4 hours; free sulfadiazine concentrations were about 47 mcg/mL. After oral administration of an initial 100-mg/kg dose of sulfadiazine, followed by an additional 50 mg/kg of the drug given every 6 hours, free sulfadiazine concentrations in blood were about 70 mcg/mL. In another study, average serum concentrations of approximately 30 mcg/mL were attained within 2 hours following oral administration of a single 3-g dose of sulfadiazine; an average peak serum concentration of approximately 50 mcg/mL was reached within 6 hours followed by a gradual decrease to 30 mcg/mL within 24 hours. Approximately 10-40% of sulfadiazine in plasma is acetylated.
Sulfadiazine is distributed into most body tissues; the drug appears to cross cell membranes freely. At a plasma concentration of 100 mcg/mL, approximately 32-56% of sulfadiazine is bound to plasma proteins.
Sulfadiazine distributes into the CSF; free and total sulfadiazine CSF concentrations may reach 32-65 and 40-60% of concurrent blood concentrations, respectively. Following a single 2-g oral dose of sulfadiazine in a limited number of patients with normal meninges, average CSF concentrations were reported to be only 5-13% of those in plasma. If the meninges are inflamed, however, higher sulfonamide CSF concentrations may be reached.
Sulfadiazine is excreted largely in urine; urinary sulfadiazine concentrations usually are 10-25 times those attained in serum. Approximately 10% of a single oral dose of sulfadiazine can be recovered intact or as the N 4-acetyl derivative, glucuronide, and other metabolites within 6 hours and approximately 50% of a single dose is excreted in the urine within 24 hours; 60-85% can be recovered within 72 hours. About 15-40% of the sulfadiazine in the urine is in the N 4-acetylated form; about 43-60% is excreted unchanged. Sulfadiazine and N 4-acetyl sulfadiazine have relatively low solubilities in acid media. At pH 5, 6, 7, and 8, sulfadiazine has solubilities of about 13, 18, 68, and 570 mg/dL, respectively. The N 4-acetyl derivative at the same pH values has solubilities of approximately 20 mg, 42 mg, 260 mg, and 2.44 g per dL, respectively.
Chemistry and Stability
Sulfadiazine is an intermediate-acting antibacterial sulfonamide. Sulfadiazine occurs as a white or slightly yellow, odorless or nearly odorless powder and is practically insoluble in water and sparingly soluble in alcohol.
Sulfadiazine tablets should be stored in well-closed, light-resistant containers at 15-30°C. Sulfadiazine is stable in air but slowly darkens on exposure to light.
For further information on chemistry and stability, mechanism of action, spectrum, resistance, pharmacokinetics, uses, cautions, drug interactions, and dosage and administration of sulfadiazine.
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Synonyms of Pyrimethamine *:
CD, Chloridin, Chloridine, Chloridyn, Diaminopyritamin, Ethylpyrimidine, Pirimetamin, Pirimetamina, Primethamine, Pyremethamine, Pyrimethamin, Pyrimethamine Hcl
* Official titles and synonyms used in the British, European, and US Pharmacopoeias. INNs in the other main official languages (French, Latin, and Spanish) have also been included in the list of synonyms where these differ from the English INN.
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Therapeutic classes of Pyrimethamine:
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