Cotrimoxazole
Synonyms :
Sulphamethoxazole, TMP-SMX, Trimethoprim, Trimethoprim + Sulphamethoxazole
Mechanism :
Co-trimoxazole, (i.e. trimethoprim and sulfamethoxazole) is a synthetic antibacterial combination product.
Sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA). Trimethoprim blocks the production of tetrahydrofolic acid from dihydrofolic acid by binding to and reversibly inhibiting the required enzyme, dihydrofolate reductase. Thus, co-trimoxazole blocks two consecutive steps in the biosynthesis of nucleic acids and proteins essential to many bacteria.
Indication :
- Pneumocystis carinii pneumonia
- Toxoplasmosis
- Nocardiosis
- Urinary tract infection
- Skin and soft tissue infections
- Bacillary dysentery
- Otitis media
Contraindications :
Co-trimoxazole is contraindicated in patients with a known hypersensitivity to trimethoprim or sulfonamides and in patients with documented megaloblastic anemia due to folate deficiency. It is also contraindicated in pregnant patients at term and in nursing mothers, because sulfonamides pass the placenta and are excreted in the milk and may cause kernicterus and in pediatric patients less than 2 months of age.
Dosing :
<2 months: Contraindicated.
Mild to Moderate Infections:
>2 months: 8-10 mg TMP/kg/day in 2 divided doses.
>2 months: 15-20 mg TMP/kg/day PO in 4 divided doses. Max: 320 mg/day trimethoprim and 1.6 g/day of sulfamethoxazole.
Give for 5 days in shigellosis, 3 days for cholera and 21 days for PCP.
Prophylaxis: 150 mg TMP/m²/day PO in 2 divided doses hr for 3 days/week on consecutive or alternate days or 2 mg TMP/kg/dose PO every day, or 5 mgTMP/kg/dose two times weekly.
Adverse Effect :
Anorexia, nausea, vomiting, rash, urticaria, hypersensitivity reaction, Stevens-Johnson syndrome, Toxic epidermal necrolysis, agranulocytosis, aplastic anemia, hyponatremia, QT prolongation resulting in ventricular tachycardia and torsade de pointes.
Interaction :
Warfarin: Potentiates the anticoagulant activity of warfarin.
Phenytoin: Prolongs the half-life .
Methotrexate: A folate supplement should be considered.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 30-50 | Dose as in normal renal function |
| 15-30 | 50% of dose; PCP: 60 mg/kg twice daily for 3 days then 30 mg/kg twice daily |
| <15 | 50% of dose; PCP: 30 mg/kg twice daily. (This should only be given if haemodialysis facilities are available) |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Not dialysed. Dose as in GFR<15 mL/min |
| HD | Dialysed. Dose as in GFR<15 mL/ min |
| HDF/High flux | Dialysed. Dose as in GFR<15 mL/ min |
| CAV/VVHD | Dialysed. Dose as in GFR=15– 30 mL/min |
Hepatic Dose :
It is metabolized by the liver. Dosage adjustments may be necessary in patients with hepatic impairment.