Sulfadiazine Sodium

(BANM, rINN)
Synonyms: Sodium Sulfadiazine; Soluble Sulphadiazine; Sulfadiazina de sodio; Sulfadiazina sódica; Sulfadiazine sodique; Sulfadiazinum Natricum; Sulphadiazine Sodium.
Cyrillic synonym: Сульфадиазин Натрий.

💊 Chemical information

Chemical formula: C10H9N4NaO2S = 272.3.
CAS — 547-32-0.
ATC — J01EC02.

Pharmacopoeias.

In Chin. and US.

USP 31

(Sulfadiazine Sodium). A white powder. Soluble 1 in 2 of water; slightly soluble in alcohol. On prolonged exposure to humid air it absorbs carbon dioxide with the liberation of sulfadiazine and becomes incompletely soluble in water. Store in airtight containers at a temperature of 25°, excursions permitted between 15° and 30°. Protect from light.

Incompatibility.

Solutions of sulfadiazine sodium are alkaline, and incompatibility may reasonably be expected with acidic drugs or with preparations unstable at high pH. In the UK, licensed product information states that sulfadiazine sodium injection is incompatible with fructose, iron salts, and salts of heavy metals.

💊 Adverse Effects, Treatment, and Precautions

As for Sulfamethoxazole. Because of the low solubilities of sulfadiazine and its acetyl derivative in urine, crystalluria is more likely after use of sulfadiazine than after sulfamethoxazole. Sulfadiazine sodium solution is strongly alkaline and it should therefore be given intravenously in a strength not exceeding 5%, over at least 10 minutes. For the same reason, intramuscular injections are painful and sulfadiazine sodium should not be given by intrathecal or subcutaneous injection.

Carnitine deficiency.

Hyperammonaemia and carnitine deficiency developed in an immunocompromised patient given sulfadiazine and pyrimethamine for the treatment of toxoplasmosis.1
1. Sekas G, Harbhajan SP. Hyperammonemia and carnitine deficiency in a patient receiving sulfadiazine and pyrimethamine. Am J Med 1993; 95: 112–13.

Effects on the eyes.

Numerous white stone-like concretions of sulfadiazine occurred in the conjunctiva of a woman who had used sulfadiazine eye drops for about 1 year.1
1. Boettner EA, et al. Conjunctival concretions of sulfadiazine. Arch Ophthalmol 1974; 92: 446–8.

Effects on the kidneys.

Reports of crystalluria and renal failure associated with the use of sulfadiazine in immunocompromised patients,1-8 including the suggestion that AIDS patients may be particularly prone to sulfadiazine-induced renal toxicity.3Renal failure and leucopenia in a patient treated with sulfadiazine silver for pyoderma gangrenosum were thought to be due to systemic absorption of the silver component.9
1. Goadsby PJ, et al. Acquired immunodeficiency syndrome (AIDS) and sulfadiazine-associated acute renal failure. Ann Intern Med 1987; 107: 783–4
2. Ventura MG, et al. Sulfadiazine revisited. J Infect Dis 1989; 160: 556–7
3. Simon DI, et al. Sulfadiazine crystalluria revisited: the treatment of Toxoplasma encephalitis in patients with acquired immunodeficiency syndrome. Arch Intern Med 1990; 150: 2379–84
4. Díaz F, et al. Sulfadiazine-induced multiple urolithiasis and acute renal failure in a patient with AIDS and Toxoplasma encephalitis. Ann Pharmacother 1996; 30: 41–2
5. Guitard J, et al. Sulfadiazine-related obstructive urinary tract lithiasis: an unusual cause of acute renal failure after kidney transplantation. Clin Nephrol 2005; 63: 405–7
6. Solano Remírez M, et al. Insuficiencia renal por sulfadiazina en paciente VIH con toxoplasmosis cerebral. An Med Interna 2005; 22: 395–6
7. Hyvernat H, et al. Insuffisance rénale aiguë obstructive lors d’un traitement par sulfadiazine. Presse Med 2006; 35: 423–4
8. de la Prada Alvarez FJ, et al. Insuficiencia renal aguda por depósito de cristales de sulfadiacina. An Med Interna 2007; 24: 235–8
9. Chaby G, et al. Insuffisance rénale aiguë après application topique de sulfadiazine argentique. Ann Dermatol Venereol 2005; 132: 891–3.

Effects on the salivary glands.

Enlargement of the salivary glands (sialadenitis) has been reported1 in a patient who received a preparation containing sulfadiazine; complete recovery followed within 3 days of stopping therapy. Rechallenge confirmed that sulfadiazine was the causative agent.
1. Añíbarro B, Fontela JL. Sulfadiazine-induced sialadenitis. Ann Pharmacother 1997; 31: 59–60.

💊 Interactions

💊 Antimicrobial Action

💊 Pharmacokinetics

Sulfadiazine is readily absorbed from the gastrointestinal tract, peak blood concentrations being reached 3 to 6 hours after a single dose; 20 to 55% has been reported to be bound to plasma proteins. It penetrates into the CSF within 4 hours of an oral dose to produce therapeutic concentrations which may be more than half those in the blood. Up to 40% of sulfadiazine in the blood is present as the acetyl derivative. The half-life of sulfadiazine is about 10 hours; it is prolonged in renal impairment. About 50% of a single dose of sulfadiazine given by mouth is excreted in the urine in 24 hours; 15 to 40% is excreted as the acetyl derivative.
About 30% is excreted unchanged in both fast and slow acetylators when the urine is acidic whereas about 75% is excreted unchanged by slow acetylators when the urine is alkaline. The half-life of sulfadiazine ranges from 7 to 12 hours and that of its metabolite from 8 to 12 hours.1
1. Vree TB, et al. Determination of the acetylator phenotype and pharmacokinetics of some sulphonamides in man. Clin Pharmacokinet 1980; 5: 274–94.

💊 Uses and Administration

Sulfadiazine is a short-acting sulfonamide that has been used similarly to sulfamethoxazole in the treatment of infections due to susceptible organisms. It has been used in the treatment of nocardiosis and lymphogranuloma venereum, and has been given for the prophylaxis of rheumatic fever in penicillin-allergic patients. For details of these infections and their treatment, see Choice of Antibacterial. Sulfadiazine is also given with pyrimethamine for the treatment and prevention of relapse of toxoplasmosis and has been tried in disseminated Acanthamoeba infection. In the treatment of susceptible infections, sulfadiazine may be given orally in usual initial doses of 2 to 4 g, followed by up to 6 g daily in divided doses. A dose in children is 75 mg/kg initially, then 150 mg/kg daily in divided doses to a maximum of 6 g daily. Sulfadiazine is used in infants less than 2 months of age for congenital toxoplasmosis; an oral dose of 50 mg/kg twice daily for 12 months has been suggested by the BNFC for use in neonates. Immunocompromised patients who have toxoplasmosis should be given a dose of 4 to 6 g daily in 4 divided doses for at least 6 weeks, followed by a suppressive dose of 2 to 4 g daily, which should continue indefinitely. Pyrimethamine should always be given as well. For the prophylaxis of rheumatic fever, patients weighing less than about 30 kg are given 500 mg once daily, while those over 30 kg may receive 1 g once daily. Sulfadiazine is also given intravenously as the sodium salt. Sulfadiazine sodium 1.09 g is equivalent to about 1 g of sulfadiazine. The usual dose is the equivalent of sulfadiazine 2 to 3 g initially, then 1 g four times daily for 2 days; subsequent treatment is given orally. Children and infants over 2 months of age may be given the equivalent of 50 mg/kg initially, followed by 25 mg/kg four times daily. Intravenous doses of sulfadiazine sodium are given by infusion or by slow intravenous injection of a solution containing up to 5% sulfadiazine. It may be diluted with sodium chloride 0.9%. Sulfadiazine sodium has been given by deep intramuscular injection, but great care must be taken to prevent damage to subcutaneous tissues; the intravenous route is preferred. Sulfadiazine has been used with trimethoprim as cotrimazine. Sulfadiazine has also been used with other sulfonamides, particularly sulfamerazine and sulfadimidine, to reduce the problems of low solubility in urine.

💊 Preparations

BP 2008: Sulfadiazine Injection; USP 31: Sulfadiazine Sodium Injection; Sulfadiazine Tablets; Trisulfapyrimidines Oral Suspension; Trisulfapyrimidines Tablets.

Proprietary Preparations

Arg.: Sulfatral; Braz.: Neo Sulfazina†; Suladrin; Sulfadiazinac†; Fr.: Adiazine†; Gr.: Adiazine; Mex.: Bioarginol-C; Sularyn; Port.: Labdiazina. Multi-ingredient: Arg.: Afonisan; Anginotrat; Pastillas Lorbi; Sulfatral-Cerio†; Austria: Ophcillin N; Rhinon; Braz.: Tr ig lo be ; Canad.: Coptin; Fin.: Ditrim; Trimetin Duplo; Ger.: Sterinor†; Urospasmon sine†; Urospasmon†; Gr.: Geypirina; India: Aubril; Zad-G; Indon.: Trisulfa; Malaysia: Balin; Beaglobe; Triglobe†; Trisulprim†; Trizine; Mex.: Agin; Estrefen; Philipp.: Triglobe; Trizine; Port.: Broncodiazina; Singapore: Balin; Swed.: Trimin sulfa†; Thai.: Sulfatril; Turk.: Sulfatrim; Venez.: Esterinor†.
Published May 08, 2019.