Sulphamethoxazole
Sulphamethoxazole Uses, Dosage, Side Effects, Food Interaction and all others data.
Sulphamethoxazole is a bacteriostatic sulfonamide antibiotic that interferes with folic acid synthesis in susceptible bacteria. It is generally given in combination with trimethoprim, which inhibits a sequential step in bacterial folic acid synthesis - these agents work synergistically to block two consecutive steps in the biosynthesis of nucleic acids and proteins which are necessary for bacterial growth and division, and using them in conjunction helps to slow the development of bacterial resistance. In this combination, sulfamethoxazole is useful for the treatment of a variety of bacterial infections, including those of the urinary, respiratory, and gastrointestinal tracts.
Sulphamethoxazole is a bacteriostatic sulfonamide antibiotic that inhibits a critical step in bacterial folate synthesis. It is generally given in combination with trimethoprim, a dihydrofolate reductase inhibitor, which inhibits the reduction of dihydrofolic acid to tetrahydrofolic acid. Studies have shown that bacterial resistance develops more slowly with the combination of the two drugs than with either trimethoprim or sulfamethoxazole alone, as together they inhibit sequential steps in the bacterial folate synthesis pathway.
Sulfonamides, including sulfamethoxazole, have been implicated in hypersensitivity reactions - these agents should be discontinued at the first sign of a developing rash, as this may signal the start of a more severe reaction such as Stevens-Johnson syndrome or toxic epidermal necrolysis. Sulphamethoxazole treatment may contribute to folate deficiency and should therefore be used with caution in patients at a higher risk of developing a deficiency. Hemolysis has been observed in patients with glucose-6-phosphate dehydrogenase deficiency who are using sulfamethoxazole/trimethoprim.
| Trade Name | Sulphamethoxazole |
| Availability | Prescription only |
| Generic | Sulfamethoxazole |
| Sulfamethoxazole Other Names | Sulfamethoxazole, Sulfametoxazol, Sulphamethoxazole |
| Related Drugs | amoxicillin, doxycycline, ciprofloxacin, cephalexin, metronidazole, azithromycin, clindamycin, ceftriaxone, levofloxacin, Augmentin |
| Type | |
| Formula | C10H11N3O3S |
| Weight | Average: 253.278 Monoisotopic: 253.052111923 |
| Protein binding | Sulfamethoxazole is approximately 70% bound to plasma proteins, primarily to albumin. |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Sulphamethoxazole is an oral sulfonamide antibiotic, given in combination with trimethoprim, used to treat a variety of infections of the urinary tract, respiratory system, and gastrointestinal tract.
Sulphamethoxazole 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.
In Canada, additional indications include the adjunctive treatment of cholera, treatment of bacillary dysentery, nocardiosis, and second-line treatment of brucellosis in combination with gentamicin or rifampicin.
Sulphamethoxazole is also used to associated treatment for these conditions: Acute Exacerbation of Chronic Bronchitis (AECB) caused by susceptible bacteria, Acute Otitis Media caused by susceptible bacteria, Brucellosis, Dysentery, Bacillary, Nocardiosis, Pneumocystis Jirovecii Pneumonia, Urinary Tract Infection caused by susceptible bacteria, Susceptible Cholera, Susceptible Enteritis infectious caused by Shigella flexneri, Susceptible Enteritis infectious caused by Shigella sonnei, Susceptible Travelers' Diarrhea caused by Enterotoxigenic E. Coli (ETEC) Infection
How Sulphamethoxazole works
Sulphamethoxazole is a sulfonamide that inhibits bacterial dihydrofolic acid synthesis due to its structural similarity to an endogenous substrate, para-aminobenzoic acid (PABA). Most bacteria meet their need for folic acid by synthesizing it from PABA, as opposed to Animalia that require exogenous folic acid sources. Sulphamethoxazole competitively inhibits dihydropteroate synthase, the enzyme responsible for bacterial conversion of PABA to dihydrofolic acid. Inhibition of this pathway prevents the synthesis of tetrahydrofolate and, ultimately, the synthesis of bacterial purines and DNA, resulting in a bacteriostatic effect.
Toxicity
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.
Food Interaction
No interactions found.Sulphamethoxazole Alcohol interaction
[Moderate]
Two cases have been reported in which patients on sulfamethoxazole-trimethoprim therapy, after consuming beer, reported flushing, heart palpitations, dyspnea, headache, and nausea (disulfiram - alcohol type reactions).
First-generation sulfonylureas have been reported to cause facial flushing when administered with alcohol by inhibiting acetaldehyde dehydrogenase and subsequently causing acetaldehyde accumulation.
Since sulfamethoxazole is chemically related to first-generation sulfonylureas, a disulfiram-like reaction with products containing sulfamethoxazole is theoretically possible.
However, pharmacokinetic/pharmacodynamic data are lacking and in addition, the two reported cases cannot be clearly attributed to the concomitant use of sulfamethoxazole-trimethoprim and alcohol.
Patients should be alerted to the potential for this interaction and although the risk for this interaction is minimal, caution is recommended while taking sulfamethoxazole-trimethoprim concomitantly with alcohol.
Sulphamethoxazole Drug Interaction
Moderate: celecoxibMinor: albuterol, sertralineUnknown: fluticasone / salmeterol, aspirin, diphenhydramine, ubiquinone, duloxetine, apixaban, omega-3 polyunsaturated fatty acids, pregabalin, levothyroxine, acetaminophen, acetaminophen, cyanocobalamin, ascorbic acid, cholecalciferol, alprazolam, rivaroxaban, cetirizine
Sulphamethoxazole Disease Interaction
Major: colitis, hematologic toxicity, hypersensitivity reactions, liver disease, porphyria, renal dysfunctionModerate: crystalluria, hemodialysis, urinary obstruction
Volume of Distribution
The volume of distribution sulfamethoxazole following a single oral dose was found to be 13 L. Sulphamethoxazole distributes into sputum, vaginal fluid, middle ear fluid, breast milk, and the placenta.
Elimination Route
Sulphamethoxazole is rapidly absorbed following oral administration and has a bioavailability of 85-90%. The Tmax is approximately 1-4 hours following oral administration, and the Cmax at steady-state is 57.4 - 68.0 μg/mL.
Half Life
The average serum half-life of sulfamethoxazole is 10 hours and may be increased in patients with severely impaired renal function.
Clearance
The oral and renal clearance of sulfamethoxazole have been estimated as 1.2 ± 0.2 and 0.22 ± 0.05 L/h, respectively.
Elimination Route
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.
Innovators Monograph
You find simplified version here Sulphamethoxazole
