Usage
Sulfamethopyrazine + Trimethoprim is a combination antibiotic used to treat various bacterial infections. It is particularly effective against infections caused by susceptible strains of bacteria. This medication is prescribed for conditions like urinary tract infections, acute otitis media, bronchitis, shigellosis, traveler’s diarrhea, and Pneumocystis jirovecii pneumonia.
Pharmacological Classification: Antibiotic (Sulfonamide antibiotic combined with dihydrofolate reductase inhibitor).
Mechanism of Action: Sulfamethopyrazine, a sulfonamide, interferes with bacterial folic acid synthesis. Trimethoprim inhibits dihydrofolate reductase, another enzyme crucial in bacterial folic acid production. Together, they synergistically block two sequential steps in the folic acid pathway, inhibiting bacterial growth and often leading to bacterial death.
Alternate Names
This drug combination is often referred to as Sulfamethoxazole-Trimethoprim (SMX-TMP) or Co-trimoxazole.
Brand Names: Bactrim, Bactrim DS, Septra, Septra DS, Co-trimoxazole.
How It Works
Pharmacodynamics: Sulfamethopyrazine and Trimethoprim disrupt bacterial folic acid synthesis, which is essential for the production of purines and pyrimidines, the building blocks of DNA and RNA. This leads to the inhibition of bacterial growth and often results in bacterial death.
Pharmacokinetics: Both drugs are well-absorbed orally. Sulfamethoxazole is metabolized in the liver by the CYP450 system, and Trimethoprim undergoes minimal hepatic metabolism. Both are primarily excreted in the urine, with half-lives ranging from 8-12 hours (Sulfamethoxazole and Trimethoprim) and increased in renal failure.
Mode of Action: This combination works by sequentially blocking two enzymes in the bacterial folic acid synthesis pathway: dihydropteroate synthase (by Sulfamethoxazole) and dihydrofolate reductase (by Trimethoprim). This dual inhibition provides synergistic bactericidal activity.
Elimination Pathways: Primarily renal excretion. Hepatic metabolism plays a role for sulfamethoxazole, with the involvement of the CYP2C9 enzyme.
Dosage
Standard Dosage
Adults:
- For most infections: 160 mg Trimethoprim / 800 mg Sulfamethoxazole (one double-strength tablet) every 12 hours for 10 to 14 days.
Children:
- Dosing is weight-based, typically using the Trimethoprim component at 8-12 mg/kg/day divided every 12 hours. Pediatric safety considerations include monitoring for kernicterus in neonates and young infants, as sulfonamides can displace bilirubin.
Special Cases:
- Elderly Patients: Close monitoring is necessary, and dose adjustments may be needed depending on renal function.
- Patients with Renal Impairment: Dose reduction is required depending on creatinine clearance.
- Patients with Hepatic Dysfunction: Caution should be used and monitoring is essential.
- Patients with Comorbid Conditions: Dose adjustments may be necessary for patients with diabetes, folate deficiency, or those on certain other medications.
Clinical Use Cases Specific dosing should be guided by infectious disease specialist recommendations and patient factors.
- Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use/Emergency Situations: Dosing may be adjusted depending on the severity and type of infection, usually leaning towards higher dosages and potentially IV administration.
Dosage Adjustments: Modifications based on renal/hepatic function, concurrent medications, and other factors are crucial.
Side Effects
Common Side Effects:
Nausea, vomiting, loss of appetite, rash, diarrhea, headache.
Rare but Serious Side Effects:
Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), blood dyscrasias (agranulocytosis, thrombocytopenia, aplastic anemia), allergic reactions, hyperkalemia, hyponatremia, liver damage, seizures, Clostridium difficile infection.
Long-Term Effects:
Potential for renal damage with prolonged high doses.
Adverse Drug Reactions (ADR):
Severe skin reactions, blood dyscrasias, hepatic necrosis, acute renal failure, allergic reactions (including anaphylaxis).
Contraindications
Hypersensitivity to sulfonamides, pregnancy (especially near term and during the first trimester), severe liver or kidney disease, megaloblastic anemia due to folate deficiency, infants younger than 2 months (due to the risk of kernicterus).
Drug Interactions
Warfarin, oral hypoglycemics, methotrexate, phenytoin, digoxin, dapsone, certain diuretics, some antiarrhythmics.
Pregnancy and Breastfeeding
Contraindicated in pregnancy, especially during the first trimester and near term, due to risk of congenital malformations. Use with caution during breastfeeding as it is excreted in breast milk.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial folic acid synthesis.
- Side Effects: Nausea, vomiting, rash, diarrhea, serious skin reactions, blood dyscrasias.
- Contraindications: Hypersensitivity to sulfonamides, pregnancy, severe liver/kidney disease.
- Drug Interactions: Warfarin, oral hypoglycemics, methotrexate.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy, caution during breastfeeding.
- Dosage: Varies depending on indication and patient factors. See detailed dosage section.
- Monitoring Parameters: Renal function, liver function, complete blood count, electrolytes (especially potassium and sodium).
Popular Combinations
Commonly used alone. Combining with other antibiotics may be done in severe or resistant infections.
Precautions
Monitor for rash and other hypersensitivity reactions. Consider pre-screening for G6PD deficiency. Caution in patients with renal or hepatic impairment, folate deficiency, or porphyria. Increased sun sensitivity can occur.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Sulfamethopyrazine + Trimethoprim?
A: Dosage depends on the patient’s age, weight, renal function, and the infection being treated. Please refer to the detailed dosage section above.
Q2: What are the common side effects?
A: Common side effects include nausea, vomiting, rash, and diarrhea.
Q3: Is it safe to use during pregnancy?
A: No, it is contraindicated in pregnancy, especially in the first trimester and near term.
Q4: What are the serious side effects to watch out for?
A: Serious side effects include severe skin reactions, blood disorders, hyperkalemia, and liver damage.
Q5: What are the major drug interactions?
A: Important drug interactions can occur with warfarin, oral hypoglycemics, and methotrexate.
Q6: What should be monitored in patients on this medication?
A: Renal and liver function, complete blood count, and electrolyte levels should be monitored.
Q7: Can it be used in patients with renal impairment?
A: Yes, but the dosage must be adjusted based on creatinine clearance.
Q8: What are the contraindications for this drug?
A: Contraindications include hypersensitivity to sulfonamides, pregnancy, and severe liver or kidney disease.
Q9: How does this drug combination work?
A: Sulfamethopyrazine and trimethoprim work together to inhibit different steps in the bacterial folic acid synthesis pathway, leading to bacterial death.
Q10: What patient education should be provided?
A: Patients should be advised to drink plenty of fluids, report any rashes immediately, and complete the full course of treatment. They should also be informed about potential drug interactions and the importance of follow-up monitoring.
