Usage
Sulfamethoxazole is a sulfonamide bacteriostatic antibiotic. It is rarely used alone and is most commonly used in combination with trimethoprim. This combination is effective in treating a wide array of bacterial infections, including urinary tract infections (UTIs), otitis media, bronchitis, shigellosis, traveler’s diarrhea, and Pneumocystis jirovecii pneumonia (PJP). It inhibits bacterial growth by interfering with the synthesis of folic acid, a crucial component for bacterial DNA synthesis.
Alternate Names
Sulfamethoxazole is often referred to as SMX or SMZ. When combined with trimethoprim, the combination is known as co-trimoxazole, TMP-SMX, TMP-SMZ, or TMP-sulfa. Popular brand names include Bactrim and Septra.
How It Works
Pharmacodynamics: Sulfamethoxazole is a sulfonamide that acts by competitively inhibiting dihydropteroate synthase, a bacterial enzyme essential for folic acid synthesis. This inhibition disrupts the synthesis of purines and pyrimidines, ultimately hindering bacterial DNA synthesis.
Pharmacokinetics: Sulfamethoxazole is well-absorbed orally. It is metabolized in the liver, primarily by N-acetylation, and is excreted mainly by the kidneys. Its half-life is typically 6-12 hours but increases significantly in renal failure. It can cross the placenta and is found in breast milk.
Mode of Action: Sulfamethoxazole competitively binds to dihydropteroate synthase, preventing the incorporation of para-aminobenzoic acid (PABA) into dihydropteroic acid, an intermediary in the folic acid pathway.
Elimination pathways: Sulfamethoxazole is primarily excreted through renal pathways.
Dosage
Standard Dosage
Adults:
- General infections: 800 mg sulfamethoxazole/160 mg trimethoprim every 12 hours for 10 to 14 days.
Children:
- General infections: Based on body weight. The recommended dosage is 40 mg sulfamethoxazole/8 mg trimethoprim per kg body weight per day divided into two equal doses every 12 hours for 10 days.
- PCP prophylaxis: 750 mg sulfamethoxazole/150 mg trimethoprim per m² of body surface area per day divided into two equal doses, administered 3 days a week.
Special Cases:
- Elderly patients: Dosage adjustments may be required due to age-related physiological changes.
- Renal Impairment: CrCl 15-30 mL/min: reduce dose by 50%. CrCl <15 mL/min: avoid use.
- Hepatic Dysfunction: Dosage adjustments may be required. Closely monitor liver function tests.
Clinical Use Cases
Sulfamethoxazole/trimethoprim IV administration is generally reserved for cases where oral administration is not feasible. Dosage should be adjusted according to the patient’s condition and renal function. Specific recommendations for intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations vary.
Dosage Adjustments
Adjustments are made based on renal function, liver function and patient specific considerations.
Side Effects
Common Side Effects
Nausea, vomiting, diarrhea, rash, and headache.
Rare but Serious Side Effects
Stevens-Johnson syndrome, toxic epidermal necrolysis, bone marrow suppression, acute liver failure, and allergic reactions.
Long-Term Effects
With prolonged use, potential complications may include crystalluria and kidney stones.
Adverse Drug Reactions (ADR)
Severe skin reactions and hematological abnormalities
Contraindications
Hypersensitivity to sulfonamides, megaloblastic anemia due to folate deficiency, pregnancy at term, and during nursing. Infants less than two months of age should not receive this drug.
Drug Interactions
Sulfamethoxazole can interact with warfarin, phenytoin, methotrexate, and other medications metabolized by the liver. It can potentiate the effects of sulfonylureas and increase the risk of hyperkalemia with ACE inhibitors.
Pregnancy and Breastfeeding
Sulfamethoxazole is contraindicated during pregnancy at term due to the risk of kernicterus in the newborn. It should be used cautiously during other stages of pregnancy. It’s also contraindicated during breastfeeding as it can pass into breast milk and potentially harm the infant.
Drug Profile Summary
- Mechanism of Action: Inhibits dihydropteroate synthase.
- Side Effects: Nausea, vomiting, rash, severe skin reactions, and bone marrow suppression.
- Contraindications: Sulfonamide hypersensitivity, pregnancy at term, breastfeeding, infants < 2 months old.
- Drug Interactions: Warfarin, phenytoin, methotrexate.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Varies; see above sections.
- Monitoring Parameters: Complete blood count, liver and renal function tests.
Popular Combinations
Sulfamethoxazole is most often combined with trimethoprim.
Precautions
Assess renal function before and during treatment. Encourage adequate hydration to prevent crystalluria. Monitor for signs of hypersensitivity and blood dyscrasias.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Sulfamethoxazole?
A: Sulfamethoxazole is typically dosed in combination with trimethoprim. Adult dosing for many infections is 800 mg sulfamethoxazole/160 mg trimethoprim every 12 hours. Pediatric dosing is weight-based.
Q2: What is the mechanism of action of Sulfamethoxazole?
A: Sulfamethoxazole competitively inhibits the bacterial enzyme dihydropteroate synthase, ultimately preventing the synthesis of bacterial folic acid.
Q3: What are the common side effects of Sulfamethoxazole?
A: Common side effects include nausea, vomiting, diarrhea, rash, and headache.
Q4: What are the serious side effects of Sulfamethoxazole?
A: Serious side effects may include Stevens-Johnson syndrome, toxic epidermal necrolysis, and bone marrow suppression.
Q5: Can Sulfamethoxazole be used during pregnancy?
A: Sulfamethoxazole is contraindicated near term pregnancy and during breastfeeding.
Q6: What are the contraindications to Sulfamethoxazole use?
A: Contraindications include hypersensitivity to sulfonamides, megaloblastic anemia due to folate deficiency, pregnancy at term, and during nursing. Infants less than two months of age should not be given sulfamethoxazole.
Q7: Does Sulfamethoxazole interact with other medications?
A: Yes. Significant interactions can occur with warfarin, phenytoin, and methotrexate, among others.
A: It is metabolized in the liver, predominantly through N-acetylation, and primarily excreted by the kidneys.
Q9: How should Sulfamethoxazole be administered in renal impairment?
A: Reduce the dose by 50% for CrCl 15-30 mL/min. Avoid use if CrCl is less than 15 mL/min.
Q10: Is Sulfamethoxazole effective against MRSA?
A: While Sulfamethoxazole/trimethoprim can be used for some MRSA skin infections, other agents are generally preferred. It is crucial to base treatment on local susceptibility patterns.
