Sulfamethoxazole

Sulfamethoxazole is a bacteriostatic sulfonamide antibiotic that inhibits a critical step in bacterial folate synthesis.

Sulfamethoxazole is used to treat a variety of infections of the urinary tract, respiratory system, and gastrointestinal tract.

Sulfamethoxazole is rapidly absorbed following oral administration and has a bioavailability of 85-90%. The volume of distribution sulfamethoxazole following a single oral dose was found to be 13 L. Sulfamethoxazole distributes into sputum, vaginal fluid, middle ear fluid, breast milk, and the placenta

Sulfamethoxazole metabolism is mediated primarily by arylamine N-acetyltransferase (NAT) enzymes, which are responsible for acetylation of sulfamethoxazole at its N4 position. Sulfamethoxazole may also undergo oxidation at its C5 and N4 atoms, the latter of which is catalyzed by CYP2C9. Glucuronidation of the N4 atom, likely mediated by unspecified UGT enzymes, is an additional minor route of metabolism. None of the identified metabolites of sulfamethoxazole appear to carry antimicrobial activity. The hydroxylamine metabolite of sulfamethoxazole, generated via oxidation by CYP2C9, may be further converted to a more reactive nitroso- metabolite. Elimination occurs primarily via glomerular filtration and tubular secretion in the kidneys, with urine concentrations generally considerably higher than plasma concentrations. Approximately 84.5% of a single oral dose of sulfamethoxazole is recovered in the urine within 72 hours, of which ~30% is free sulfamethoxazole and the remainder is the N4-acetylated metabolite.

The T_max is approximately 1-4 hours following oral administration, and the C_max at steady-state is 57.4 - 68.0 μg/mL.

Sulfamethoxazole shows common side effects like Nausea, vomiting, stomatitis; diarrhoea, abdominal pain

Sulfamethoxazole is available in the form of solution

Sulfamethoxazole is available in India, Germany, Canada, Italy.

Sulfamethoxazole is indicated in combination with trimethoprim, in various formulations, for the following infections caused by bacteria with documented susceptibility: urinary tract infections, acute otitis media in pediatric patients (when clinically indicated), acute exacerbations of chronic bronchitis in adults, enteritis caused by susceptible Shigella, prophylaxis and treatment of Pneumocystis jiroveci pneumonia, and travelers' diarrhea caused by enterotoxigenic E. coli.

Sulfamethoxazole is available in the form of solution.

Sulfamethoxazole is used to treat a variety of infections of the urinary tract, respiratory system, and gastrointestinal tract.

Sulfamethoxazole is an intermediate-acting sulfonamide which interferes with the synthesis of nucleic acids in sensitive organisms by blocking the conversion of PABA to the coenzyme dihydrofolic acid. Its action is bacteriostatic, although it can be bactericidal where concentrations of thymine are low in the surrounding medium. It has broad spectrum of action though its usefulness has been greatly reduced by widespread resistance.

Sulfamethoxazole is approved for use in the following clinical indications

To treat a variety of infections of the urinary tract, respiratory system, and gastrointestinal tract.

Oral

Urinary tract infections, Otitis media, Chlamydial infections, Prophylaxis of meningococcal meningitis

Adult: Initially, 2 g followed by 1 g bid. Severe infections: 1 g tid.

Child: Initially, 50-60 mg/kg, followed by 25-30 mg/kg bid. Max daily dose: 75mg/kg.

Sulfamethoxazole is available in various strengths as 4 mL, 10 mL, 30 mL.

Sulfamethoxazole is available in the form of solution.

• Dosage Adjustment in Kidney Patient

Oral, IV: There are no dosage adjustments provided in the manufacturer's labeling.

• Dosage Adjustment in Hepatic impairment Patient

Oral, IV: There are no dosage adjustments provided in the manufacturer's labeling.

Severe renal or hepatic impairment, blood disorders, hypersensitivity to sulfonamides, porphyria, SLE, infants <2 mth, pregnancy (3rd trimester) and lactation.

Common Adverse effects:

Nausea, vomiting, anorexia, diarrhea, hypersensitivity reactions, blood disorders, serum sickness-like syndrome, hypoglycemia, hypothyroidism, pseudomembranous colitis, kernicterus in premature neonates.

Concomitant use with antitussives may lead to a build-up of secretions due to suppressed cough reflex; avoid concurrent use. May increase the vasodilatory and platelet aggregation-inhibiting effect of glyceryl trinitrate.

The common side effects of Sulfamethoxazole include the following Nausea, vomiting, anorexia, diarrhea, hypersensitivity reactions, blood disorders, serum sickness-like syndrome, hypoglycemia, hypothyroidism, pseudomembranous colitis, kernicterus in premature neonates.

The oral LD₅₀ of sulfamethoxazole in mice and rats is 2300 mg/kg and 6200 mg/kg, respectively.

Signs or symptoms of sulfonamide overdose include anorexia, colic, nausea, vomiting, dizziness, headache, drowsiness, and unconsciousness. Less common symptoms may include pyrexia, hematuria, and crystalluria. Later manifestations of overdose may include blood dyscrasias and jaundice. Treatment should be symptomatic and supportive, and may include gastric lavage or forced emesis if applicable. Monitor patient lab work for evidence of blood dyscrasias or electrolyte imbalances.

Pharmacodynamic

Sulfamethoxazole is an intermediate-acting sulfonamide which interferes with the synthesis of nucleic acids in sensitive organisms by blocking the conversion of PABA to the coenzyme dihydrofolic acid. Its action is bacteriostatic, although it can be bactericidal where concentrations of thymine are low in the surrounding medium. It has broad spectrum of action though its usefulness has been greatly reduced by widespread resistance.

Pharmacokinetics

• Absorption: Sulfamethoxazole is rapidly absorbed following oral administration and has a bioavailability of 85-90%. The T_max is approximately 1-4 hours following oral administration, and the C_max at steady-state is 57.4 - 68.0 μg/mL.
• Distribution: The volume of distribution sulfamethoxazole following a single oral dose was found to be 13 L. Sulfamethoxazole distributes into sputum, vaginal fluid, middle ear fluid, breast milk, and the placenta
• Metabolism: Sulfamethoxazole metabolism is mediated primarily by aryl amine N-acetyltransferase (NAT) enzymes, which are responsible for acetylation of sulfamethoxazole at its N4 position. Sulfamethoxazole may also undergo oxidation at its C5 and N4 atoms, the latter of which is catalyzed by CYP2C9. Glucuronidation of the N4 atom, likely mediated by unspecified UGT enzymes, is an additional minor route of metabolism. None of the identified metabolites of sulfamethoxazole appear to carry antimicrobial activity. The hydroxylamine metabolite of sulfamethoxazole, generated via oxidation by CYP2C9, may be further converted to a more reactive nitroso- metabolite

• Excretion: Elimination occurs primarily via glomerular filtration and tubular secretion in the kidneys, with urine concentrations generally considerably higher than plasma concentrations. Approximately 84.5% of a single oral dose of sulfamethoxazole is recovered in the urine within 72 hours, of which ~30% is free sulfamethoxazole and the remainder is the N4-acetylated metabolite.

• https://www.rxlist.com/dopram-drug.htm
• https://www.mims.com/india/drug/info/Sulfamethaoxazole?type=full&mtype=generic
• https://go.drugbank.com/drugs/DB00561
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003846/