Co-trimoxazole

Oral Antibiotics

Drug class: Sulfonamides

Co-trimoxazole (SEPTRIN)（中文：複方新諾明）; Trimethoprim (TMP) 80 mg and sulfamethoxazole (SMX) 400 mg, is a combination antibiotic.

Common Strengths

• Oral Tablets: 80 mg trimethoprim and 400 mg sulfamethoxazole
• Oral Suspension: 40 mg trimethoprim and 200 mg sulfamethoxazole per 5 mL
• Intravenous Solution: 16 mg trimethoprim and 80 mg sulfamethoxazole per mL

Drug Trade Names

Common trade names include:

• Bactrim
• Septrin

Drug Usage

TMP-SMX is used to treat:

• Urinary tract infections (UTIs)
• Pneumocystis jirovecii pneumonia (PCP)
• Shigellosis
• Bronchitis
• Traveler's Diarrhea

Mechanism of Action

TMP-SMX acts synergistically by inhibiting two consecutive steps in the bacterial folate synthesis pathway:

• Sulfamethoxazole inhibits the conversion of para-aminobenzoic acid (PABA) to dihydropteroic acid.
• Trimethoprim inhibits dihydrofolate reductase, preventing the conversion of dihydrofolate to tetrahydrofolate.

Route of Administration

• TMP-SMX can be administered orally or intravenously

Dosages

• Normal Adults
  • Typical dose for UTIs: 800 mg sulfamethoxazole and 160 mg trimethoprim every 12 hours for 5 days. Renal Dosing Based on eGFR:
    • For eGFR ≥30 mL/min/1.73 m²: standard dosing.
    • For eGFR <30 mL/min/1.73 m²: caution is advised; doses should be adjusted accordingly.

Side Effects

Frequency	Adverse reactions
Common Side Effects	Nausea
	Vomiting
	Skin rash
Serious Side Effects	Severe allergic reactions (e.g. Stevens-Johnson syndrome)
	Blood dyscrasias (e.g. thrombocytopenia)
	Hyperkalemia (especially in patients with renal impairment)

Pharmacokinetics

• Absorption: Peak serum concentrations are typically reached within 1 to 4 hours after oral administration.
• Elimination Half-Life: The elimination half-lives are about 10-11 hours for trimethoprim and 9-11 hours for sulfamethoxazole in healthy individuals. In cases of renal impairment, these half-lives can extend significantly, necessitating dosage adjustments.
• Both drugs are primarily eliminated via the kidneys.
• Onset Time: Typically within hours after administration.
• Duration of Action: Approximately 12 hours for the oral formulation.

Drug Precautions

Pregnancy

Contraindicated due to potential risks to the fetus.

Breastfeeding

Caution is advised; both components can pass into breast milk.

Children and Elderly

Use with caution; dosage adjustments may be necessary for pediatric patients under two months old and elderly patients with renal impairment.

Drug Monitoring Items

Monitor renal function (creatinine levels) and potassium levels, and potassium levels, especially in patients with pre-existing kidney issues.

Drug Interactions

Notable interactions include:

• Anticoagulants (e.g. Warfarin): Co-trimoxazole can enhance the anticoagulant effect of warfarin, increasing the risk of bleeding.
• Methotrexate: The concurrent use of co-trimoxazole with methotrexate lead to severe bone marrow suppression.
• Potassium-Sparing Diuretics and ACE Inhibitors: can increase the risk of hyperkalemia. Patients should be closely monitored for potassium levels, specially in those with renal impairment or other risk factors for cardiac issues.

Immunosuppressants (e.g. Tacrolimus, Ciclosporin): There is a potential for additive nephrotoxicity when co-trimoxazole is used with immunosuppressants like tacrolimus or ciclosporin. Frequent monitoring of drug levels and renal function is recommended if these drugs must be used together.

• Phenytoin: Co-trimoxazole can prolong the half-life of phenytoin, necessitating careful monitoring of serum levels to prevent toxicity.
• Diabetes Medications (e.g. Gliclazide, Glipizide): May increase the risk of hypoglycemia. Blood glucose levels should be monitored closely, and doses may need adjustment.
• Digoxin: Can increase digoxin exposure, which might lead to toxicity; therefore, monitoring digoxin levels is crucial when co-administering these drugs.
• Clozapine: Co-trimoxazole is contraindicated due to the risk of neutropenia.
• Amiodarone: There may be an increased risk of ventricular arrhythmias, particularly in patients with other risk factors for QT prolongation.

FAQ

How Should I Take the Tablet?

Take with a full glass of water, preferably on an empty stomach for better absorption.

What Should I Avoid while Taking?

Avoid Excessive sun exposure; use sunscreen as TMP-SMX can increase sensitivity to sunlight.

What Happens if I Miss a Dose?

Take it as soon as you remember unless it is close to the time for your next dose. Do not double up on doses.