Usage
Sulfamethoxazole + Trimethoprim is prescribed for various bacterial infections, including urinary tract infections, otitis media, bronchitis, shigellosis, traveler’s diarrhea, and Pneumocystis jiroveci pneumonia (PCP). It’s also used for prophylaxis of PCP. Pharmacologically, it is classified as an antibiotic. The drug acts by inhibiting sequential steps in bacterial folic acid synthesis, ultimately disrupting DNA and protein synthesis.
Alternate Names
Sulfamethoxazole + Trimethoprim is also known as co-trimoxazole. Brand names include Bactrim, Bactrim DS, Septra, and Cotrim.
How It Works
Pharmacodynamics: Sulfamethoxazole + Trimethoprim exerts a synergistic bactericidal effect. Sulfamethoxazole inhibits dihydropteroate synthase, an enzyme involved in the initial step of bacterial folic acid synthesis. Trimethoprim inhibits dihydrofolate reductase, a later step in the pathway. This combined blockade effectively disrupts bacterial DNA and protein synthesis, leading to cell death.
Pharmacokinetics: Both drugs are well-absorbed orally. They are metabolized in the liver and excreted primarily by the kidneys. Sulfamethoxazole undergoes acetylation, while trimethoprim is partially metabolized and primarily excreted unchanged. Dose adjustments are necessary in renal impairment.
Mechanism of Action: The combined action of sulfamethoxazole and trimethoprim disrupts the folic acid pathway vital for bacterial DNA and protein synthesis. These drugs don’t affect human cells because they utilize preformed folic acid.
Elimination: Primarily renal excretion, with some hepatic metabolism.
Dosage
Standard Dosage
Adults:
- Standard Dose: One double-strength tablet (800 mg sulfamethoxazole/160 mg trimethoprim) or two single-strength tablets (400 mg sulfamethoxazole/80 mg trimethoprim) every 12 hours. Alternatively, 20 mL of oral suspension (400 mg sulfamethoxazole/80 mg trimethoprim per 5 mL) every 12 hours.
- Duration: 10 to 14 days for most infections.
- Maximum Dosage: Varies depending on the infection.
Children:
- Dosage: Based on body weight (mg/kg) or body surface area (mg/m²). The usual pediatric dose is 6 to 10 mg/kg trimethoprim component per day divided every 12 hours.
- Safety: Not recommended for infants younger than 2 months.
Special Cases:
- Elderly Patients: Close monitoring for adverse effects, particularly bone marrow suppression and hyperkalemia.
- Patients with Renal Impairment: Dose reduction based on creatinine clearance.
- Patients with Hepatic Dysfunction: Caution and monitoring are advised.
- Patients with Comorbid Conditions: Consider potential interactions with medications for diabetes, cardiovascular disease, and other conditions.
Clinical Use Cases For specific medical settings like intubation, surgical procedures, mechanical ventilation, and ICU use, dosing is usually guided by infectious disease specialists and is often based on the standard dosage with potential adjustments based on clinical presentation and risk factors. The same is applied to emergency cases.
Dosage Adjustments Adjustments are made for renal and hepatic dysfunction, potential drug interactions, and other relevant factors.
Side Effects
Common Side Effects:
Nausea, vomiting, loss of appetite, and skin rash.
Rare but Serious Side Effects:
Stevens-Johnson syndrome, toxic epidermal necrolysis, bone marrow suppression, hepatitis, hyperkalemia, and seizures.
Long-Term Effects:
With prolonged use, potential for folate deficiency and peripheral neuropathy.
Adverse Drug Reactions (ADR):
Severe skin reactions (SJS/TEN), blood dyscrasias, and hepatic necrosis require immediate intervention.
Contraindications
- Hypersensitivity to sulfonamides or trimethoprim.
- Marked hepatic damage.
- Severe renal insufficiency (without monitoring).
- Megaloblastic anemia due to folate deficiency.
- Infants younger than 2 months old.
- Pregnancy (near term or first trimester without folic acid supplementation).
Drug Interactions
Sulfamethoxazole + Trimethoprim interacts with numerous drugs, including warfarin, oral hypoglycemic agents, phenytoin, methotrexate, and some diuretics. It can potentiate the effects of warfarin and sulfonylureas, increasing the risk of bleeding and hypoglycemia, respectively. Consult a drug interaction database for a comprehensive list.
Pregnancy and Breastfeeding
- Pregnancy: Contraindicated near term and in the first trimester unless supplemented with folic acid (due to the risk of neural tube defects).
- Breastfeeding: Drug is excreted in breast milk. Use with caution and only if clearly needed. Monitor the infant for kernicterus, especially in premature or jaundiced infants.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial folic acid synthesis.
- Side Effects: Nausea, vomiting, rash, SJS/TEN (rare).
- Contraindications: Sulfa allergy, severe hepatic/renal disease, pregnancy (near term/first trimester), infants <2 months.
- Drug Interactions: Warfarin, oral hypoglycemics, methotrexate.
- Pregnancy & Breastfeeding: Use with caution. Contraindicated near term/first trimester.
- Dosage: Adults: DS 1 tab BID. Children: weight-based.
- Monitoring Parameters: CBC, renal function, electrolytes (especially potassium).
Popular Combinations
Sulfamethoxazole + Trimethoprim is sometimes combined with other antibiotics for specific infections, but it is generally used alone.
Precautions
- General Precautions: Monitor for hypersensitivity, renal and hepatic function, and blood counts. Ensure adequate hydration.
- Specific Populations: See above for pregnancy, breastfeeding, children, and elderly.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Sulfamethoxazole + Trimethoprim?
A: Adults: One double-strength tablet (800 mg/160 mg) or two single-strength tablets (400 mg/80 mg) every 12 hours. Children: Dose is weight-based or based on body surface area.
Q2: What are the most common side effects?
A: Nausea, vomiting, rash, and loss of appetite.
A: Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), blood dyscrasias (e.g., agranulocytosis, thrombocytopenia), and severe allergic reactions.
Q4: Is Sulfamethoxazole + Trimethoprim safe in pregnancy?
A: Generally avoided, especially near term and in the first trimester due to potential teratogenic effects. If used during pregnancy, folic acid supplementation is recommended.
Q5: What are the contraindications for this drug?
A: Hypersensitivity to sulfa drugs, severe liver or kidney disease, megaloblastic anemia due to folate deficiency, and infants younger than two months.
Q6: How does Sulfamethoxazole + Trimethoprim work?
A: It inhibits sequential steps in bacterial folic acid synthesis, disrupting bacterial DNA and protein production.
Q7: What are the important drug interactions?
A: Warfarin, oral hypoglycemics, methotrexate, some diuretics, and other drugs that can affect potassium levels.
Q8: Can Sulfamethoxazole + Trimethoprim be used in patients with renal impairment?
A: Yes, but dosage adjustments are required based on the degree of impairment. Close monitoring is essential.
Q9: What patient education should be provided?
A: Advise patients to take the medication with food and plenty of fluids, complete the full course of therapy even if feeling better, and report any signs of rash or allergic reaction promptly. Explain potential drug interactions and the importance of informing their healthcare provider about all medications and supplements they take.
