CO-TROMOXAZOLE 480MG TABLET

Indications

• Urinary tract infections
• Pneumocystis jirovecii pneumonia
• Acute exacerbations of chronic bronchitis
• Typhoid fever
• Shigellosis
• Traveler's diarrhea

Dosage

Children: Refer to the BNF for Children for appropriate dosing recommendations based on the child's age and weight.

Adults: Refer to the BNF for specific dosing guidelines based on the indication and patient characteristics.

Mechanism of action

Cotrimoxazole works by inhibiting bacterial folate synthesis. Sulfamethoxazole is a sulfonamide that competes with para-aminobenzoic acid (PABA) for the active site of the enzyme dihydropteroate synthase, preventing the formation of dihydropteroic acid, a precursor in folate synthesis. Trimethoprim inhibits dihydrofolate reductase, an enzyme involved in converting dihydrofolate to tetrahydrofolate, which is essential for DNA synthesis. This dual mechanism results in a potent antibacterial effect.

Pharmacodynamics

The combination of trimethoprim and sulfamethoxazole results in a synergistic effect, enhancing the antibacterial activity against various gram-positive and gram-negative organisms. It is particularly effective against organisms such as Escherichia coli, Haemophilus influenzae, and Staphylococcus aureus. The combination also reduces the likelihood of developing resistance compared to using each drug alone.

Pharmacokinetics

Cotrimoxazole is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 1 to 4 hours after oral administration. The drug is widely distributed throughout body tissues and fluids. It is metabolized in the liver and eliminated primarily via the kidneys, with a half-life of approximately 8 to 10 hours for trimethoprim and 10 hours for sulfamethoxazole. Renal impairment may require dose adjustment.

Contra-indications

• Severe hypersensitivity to sulfonamides or trimethoprim
• Severe liver disease
• Severe renal impairment
• Blood dyscrasias

Adverse effects

• Rash
• Nausea
• Vomiting
• Diarrhea
• Hematological reactions (e.g., leukopenia, thrombocytopenia)
• Hepatotoxicity
• Hyperkalemia

Interactions

• Increased effect of anticoagulants (e.g., warfarin)
• Increased risk of toxicity when used with methotrexate
• May enhance the effects of other antidiabetic agents
• May decrease the effectiveness of oral contraceptives

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of hematological reactions
• Ensure adequate hydration to prevent crystalluria
• Caution in patients with a history of sulfonamide allergy

Pregnancy

Use in pregnancy is not recommended unless clearly needed, as it can affect folate metabolism.

Breast-feeding

Caution is advised; small amounts may be excreted in breast milk.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Tablets
• Suspension
• Injectable form