Sulfamethizole is a short-acting sulfonamide antibacterial agent used primarily for the treatment of urinary tract infections (UTIs) caused by susceptible bacteria. It acts by inhibiting bacterial folic acid synthesis, an essential pathway for DNA, RNA, and protein production, leading to bacteriostatic effects.
Historically, sulfamethizole was developed in the mid-20th century as part of the ongoing effort to produce effective sulfonamide derivatives with improved pharmacokinetic properties and fewer side effects. It became a commonly prescribed agent for uncomplicated UTIs, especially before the widespread availability of newer antibiotics. Although its use has declined with the advent of safer and more potent antimicrobial agents, sulfamethizole still holds clinical value in specific cases where pathogens remain susceptible or when sulfonamide combinations are preferred.
BRAND NAMES
Thiosulfil Forte: A brand name for sulfamethizole alone.
Urobiotic-250: A multi-ingredient medication that includes sulfamethizole.
Tija: Another name for Urobiotic-250.
MECHANISM OF ACTION
Sulfamethizole exerts its antibacterial effect by inhibiting bacterial folic acid synthesis, which is essential for nucleic acid and protein formation. It is a competitive antagonist of para-aminobenzoic acid (PABA), a substrate required by bacteria to synthesize dihydropteroic acid, a precursor of folic acid. By blocking the enzyme dihydropteroate synthase, sulfamethizole prevents the formation of folate, ultimately inhibiting bacterial growth. This action is bacteriostatic rather than bactericidal, meaning it stops bacterial proliferation but relies on the host’s immune system to eliminate the infection.
PHARMACOKINETICS
Absorption
Sulfamethizole is rapidly absorbed following oral administration and can also be absorbed via topical routes. Its absorption rate may be influenced by factors such as particle size and dissolution, as evidenced by studies that have utilized sulfamethizole to evaluate gastric emptying.
Distribution
The volume of distribution of sulfamethizole is relatively low, typically around 0.1–0.2 L/kg, reflecting its limited distribution beyond the extracellular fluid. It is moderately bound to plasma proteins, which helps retain the drug primarily within the vascular and interstitial compartments rather than extensive tissue penetration.
Metabolism
Sulfamethizole is partially metabolized in the liver, primarily through acetylation to form N-acetylsulfamethizole, which is generally less active than the parent drug. A small portion may also undergo oxidation or hydrolysis. Both the parent compound and its metabolites are eventually excreted in the urine, with renal clearance playing a major role in eliminating the drug from the body. Hepatic or renal impairment can alter its metabolism and clearance, potentially increasing the risk of toxicity.
Excretion
Sulfamethizole and its metabolites are primarily excreted via the kidneys. Approximately 50–70% of the administered dose is eliminated in the urine, both as the unchanged drug and as N-acetylated metabolites. Urinary excretion is influenced by urine pH, with alkaline urine increasing solubility and reducing the risk of crystalluria. A small amount may also be excreted in the feces. Renal impairment can significantly prolong drug elimination, necessitating dose adjustments.
PHARMACODYNAMICS
Sulfamethizole is a bacteriostatic sulfonamide that inhibits bacterial growth by blocking folic acid synthesis. It competitively antagonizes para-aminobenzoic acid (PABA), preventing the formation of dihydropteroic acid, a folate precursor essential for nucleic acid and protein synthesis. Its activity is primarily effective against gram-positive and gram-negative urinary pathogens, and it relies on the host immune system to clear the infection since it does not directly kill bacteria.
ADMINISTRATION
Sulfamethizole is a sulfonamide antibiotic commonly used in combination with trimethoprim for the treatment of urinary tract infections (UTIs). It is available in oral tablets, double-strength tablets, and oral suspension forms. The dosage and duration of therapy are determined by the type of infection and patient-specific factors, such as age and renal function.
DOSAGE AND STRENGTH
Sulfamethizole is commonly administered orally, often in combination with trimethoprim. Typical formulations include:
Oral tablets: 500 mg
Double-strength tablets: 1000 mg (often in combination with trimethoprim 160 mg)
Oral suspension: Usually 125 mg/5 mL or 250 mg/5 mL
Dosage:
For uncomplicated urinary tract infections in adults, the usual dose is 1 double-strength tablet (sulfamethizole 1000 mg + trimethoprim 160 mg) twice daily for 3–7 days, depending on the severity and type of infection.
Adjustments may be required in renal impairment or in pediatric patients.
DRUG INTERACTIONS
Sulfamethizole can interact with a variety of drugs, including oral anticoagulants like warfarin, certain antihypertensive and cardiac medications, some antidiabetic agents (e.g., tolbutamide), methotrexate, and phenytoin, potentially enhancing their effects or increasing the risk of adverse reactions. It may also raise the risk of crystalluria when used with compounds that acidify urine and increase the likelihood of blood disorders when combined with clozapine. Therefore, it is essential to consult a healthcare provider before taking sulfamethizole alongside other medications, vitamins, or herbal supplements.
FOOD INTERACTIONS
When taking sulfamethizole, caution should be exercised with acidic foods and alcohol, as they may increase stomach irritation and other side effects. Maintaining adequate hydration is important to reduce the risk of kidney complications. Grapefruit juice should be avoided, as it can interfere with the drug’s metabolism.
CONTRAINDICATIONS
Sulfamethizole is contraindicated in individuals with a known hypersensitivity to sulfonamides or any component of the formulation. It should not be used in patients with severe liver or kidney impairment, as reduced clearance can increase toxicity risk. The drug is also contraindicated in those with a history of blood disorders such as aplastic anemia or agranulocytosis. Additionally, it should be avoided during late pregnancy and in newborns, due to the risk of kernicterus from displacement of bilirubin.
SIDE EFFECTS
Gastrointestinal: Nausea, vomiting, diarrhea, and loss of appetite.
Skin reactions: Rashes, hives, and increased sensitivity to sunlight (photosensitivity).
Neurological: Dizziness, headache, and lethargy.
Severe skin reactions.
Blood disorders.
Liver damage.
Kidney problems.
Intestinal infection.
Electrolyte imbalances.
Allergic reactions.
Low blood sugar.
OVERDOSE
Gastrointestinal: Nausea, vomiting, stomach cramps, and loss of appetite.
Neurological: Dizziness, headache, drowsiness, confusion, and possibly seizures or unconsciousness.
Kidney: Blood in the urine (hematuria), crystalluria, and potentially kidney failure if the overdose is severe.
Fever.
Blood disorders.
TOXICITY
Sulfamethizole toxicity arises from its nature as a sulfonamide antibiotic and can range from common gastrointestinal disturbances to rare but severe allergic or systemic reactions. Toxic effects may occur due to overdose, hypersensitivity, or interactions with other medications.
