Usage
Sulfamethopyrazine, a long-acting sulfonamide antibiotic, is primarily indicated for treating urinary tract infections and chronic bronchitis. It is also used, often in combination with pyrimethamine, for malaria prophylaxis and treatment. Its pharmacological classification is antibacterial, specifically a sulfonamide. Sulfamethopyrazine acts by inhibiting dihydropteroate synthase, a bacterial enzyme crucial for folic acid synthesis, thereby disrupting bacterial growth and multiplication.
Alternate Names
Sulfamethopyrazine is also known as Sulfalene. Brand names can vary depending on the region and manufacturer. Kelfizine is an example of a brand name.
How It Works
Pharmacodynamics: Sulfamethopyrazine exerts its bacteriostatic effect by competitively inhibiting dihydropteroate synthase. This enzyme is essential in bacteria for synthesizing dihydropteroic acid, a precursor to folic acid, which is vital for bacterial DNA and RNA synthesis. The resulting folic acid deficiency inhibits bacterial growth and reproduction.
Pharmacokinetics: Sulfamethopyrazine is well-absorbed orally. It has a long half-life (ranging from 35 to 100 hours), which allows for once-daily dosing. Metabolism occurs primarily in the liver, involving acetylation and glucuronidation. Elimination is predominantly via renal excretion, with a small amount excreted in bile.
Mode of Action: Sulfamethopyrazine, a structural analog of para-aminobenzoic acid (PABA), competes with PABA for binding to dihydropteroate synthase. This competitive inhibition blocks the incorporation of PABA into dihydropteroic acid, thus disrupting folic acid synthesis.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: The primary mechanism is competitive enzyme inhibition of dihydropteroate synthase.
Elimination Pathways: Primarily renal excretion of metabolites, with some biliary excretion.
Dosage
Standard Dosage
Adults:
The standard adult dosage for treating urinary tract infections or chronic bronchitis is typically 2 grams orally on the first day, followed by 1 gram daily until the infection clears. For malaria prophylaxis or treatment, sulfamethopyrazine is used in combination with pyrimethamine.
Children:
Pediatric dosing is based on body weight, with an initial dose of 55 mg/kg followed by 27.5 mg/kg daily.
Special Cases:
- Elderly Patients: Dosage adjustments may be necessary in the elderly due to potential age-related decline in renal function.
- Patients with Renal Impairment: Dosage reduction is crucial in patients with impaired renal function, as drug accumulation can occur.
- Patients with Hepatic Dysfunction: Caution is advised in patients with liver disease, although specific dosage adjustments may not be routinely necessary.
- Patients with Comorbid Conditions: No specific guidance was provided for patients with diabetes or cardiovascular disease.
Clinical Use Cases
The sources did not provide dosage information for clinical use cases such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dosage adjustments are needed based on renal function.
Side Effects
Common Side Effects
Common side effects can include nausea, vomiting, loss of appetite, headache, and skin rash.
Rare but Serious Side Effects
Rare but serious side effects include Stevens-Johnson syndrome, toxic epidermal necrolysis, agranulocytosis, aplastic anemia, and hepatic necrosis.
Long-Term Effects
Long-term use can potentially lead to crystalluria and kidney stones.
Adverse Drug Reactions (ADR)
Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis) and blood dyscrasias (agranulocytosis, aplastic anemia) are serious ADRs.
Contraindications
Sulfamethopyrazine is contraindicated in patients with hypersensitivity to sulfonamides, pregnant women at term, nursing mothers, and infants under two months of age (except for the treatment of congenital toxoplasmosis with pyrimethamine).
Drug Interactions
Sulfamethopyrazine can interact with several medications, including warfarin, methotrexate, and certain oral hypoglycemic agents. It can also potentiate the effects of sulfonylureas.
Pregnancy and Breastfeeding
Sulfamethopyrazine is contraindicated in pregnancy at term and during breastfeeding due to the risk of kernicterus in newborns.
Drug Profile Summary
- Mechanism of Action: Inhibits dihydropteroate synthase, disrupting bacterial folic acid synthesis.
- Side Effects: Nausea, vomiting, rash, severe skin reactions, blood dyscrasias.
- Contraindications: Sulfonamide hypersensitivity, pregnancy at term, breastfeeding, infants <2 months.
- Drug Interactions: Warfarin, methotrexate, sulfonylureas.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adults: 2g initially, then 1g daily. Children: 55 mg/kg initially, then 27.5 mg/kg daily.
- Monitoring Parameters: Renal function, complete blood count, liver function tests.
Popular Combinations
A popular combination is sulfamethopyrazine with pyrimethamine for malaria prophylaxis and treatment.
Precautions
- General Precautions: Monitor for hypersensitivity reactions and blood dyscrasias. Adequate hydration is essential to prevent crystalluria.
- Specific Populations: Contraindicated in pregnancy at term and breastfeeding. Use with caution in patients with renal or hepatic impairment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Sulfamethopyrazine?
A: Adults: 2g initially, followed by 1g daily. Children: 55 mg/kg initially, followed by 27.5 mg/kg daily.
Q2: What are the common side effects?
A: Nausea, vomiting, headache, skin rash, and loss of appetite.
Q3: What are the serious side effects?
A: Stevens-Johnson syndrome, toxic epidermal necrolysis, agranulocytosis, aplastic anemia, and hepatic necrosis.
Q4: In which conditions is Sulfamethopyrazine contraindicated?
A: Hypersensitivity to sulfonamides, pregnancy at term, breastfeeding, infants <2 months.
Q5: What are the drug interactions of Sulfamethopyrazine?
A: It can interact with warfarin, methotrexate, and sulfonylureas, among others.
Q6: Can Sulfamethopyrazine be used in pregnancy?
A: It is contraindicated during pregnancy at term due to the risk of kernicterus in the newborn.
Q7: Can Sulfamethopyrazine be used during breastfeeding?
A: It is contraindicated during breastfeeding.
Q8: What is the mechanism of action of Sulfamethopyrazine?
A: It inhibits dihydropteroate synthase, a bacterial enzyme necessary for folic acid synthesis.
Q9: How is Sulfamethopyrazine eliminated from the body?
A: Primarily through renal excretion, with some biliary excretion.
