Sulphamethoxazole + Trimethoprim (Co-trimoxazole)

Indications

Sulphamethoxazole + Trimethoprim (Co-trimoxazole) is used for: Upper and lower respiratory tract infections, Gastrointestinal tract infections, Renal and urinary tract infections, Skin and wound infections, Septicaemias

Adult Dose

Oral Acute exacerbations of chronic bronchitis ; Acute otitis media; Urinary tract infections, GI infections; Resp and urinary tract infections; Susceptible infections Adult: Tablet : 2 tablet of 480mg twice daily. In severe cases, 3 times/day. DS Tablet : 1 tablet (960mg) twice daily. Suspension : 1-2 teaspoonful twice daily. Pneumocystis (carinii) jiroveci pneumonia Up to 120 mg/kg/day in 2-4 divided doses for 14-21 days. Prophylaxis of Pneumocystis (carinii) jiroveci pneumonia 960 mg once daily for 7 days; 960 mg once daily 3 times wkly on alternate days; or 960 mg bid 3 times wkly on alternate days. Infection prophylaxis in AIDS patients 960 mg/day. Hepatic impairment: Severe: Contraindicated.

Child Dose

Child: Oral 8–10 mg TMP/kg/day q12h 2 mg TMP/kg/day for UTI prophylaxis q24h 15–20 mg TMP/kg/day for Pneumocystis (carinii) jiroveci pneumonia treatment q6–8h 150 mg TMP/m2/day, OR 5 mg TMP/kg/day for Pneumocystis (carinii) jiroveci pneumonia prophylaxis q12h, 3 times a week OR q24h

Renal Dose

Renal impairment: CrCl (ml/min) Dosage Recommendation <15 Not recommended. 15-30 Half the standard dose.

Administration

Contra Indications

Known hypersensitivity to trimethoprim or sulfonamides; severe hepatic failure or marked liver parenchymal damage, jaundice; serious haematological disorders and porphyria; severe renal insufficiency where repeated measurements of the plasma concentration cannot be performed; history of drug-induced immune thrombocytopenia w/ use of trimethoprim and/or sulfonamides; megaloblastic anaemia due to folate deficiency. Neonates <6 wk, except for the treatment/prophylaxis of P. jiroveci in infants >4 wk. Treatment of Group A β-haemolytic streptococcia. Pregnancy, esp in the period prior to birth. Concomitant use w/ clozapine. Concomitant use w/ leucovorin for the treatment of P. jiroveci in HIV positive patients.

Precautions

Patient w/ severe allergy, bronchial asthma, thyroid dysfunction. Renal and mild to moderate hepatic impairment. Lactation. Patient Counselling May impair ability to drive or operate machinery. Monitoring Parameters Monitor CBC, serum K, creatinine, BUN.

Pregnancy-Lactation

Interactions

Reduced ciclosporin concentrations in blood when used concurrently. Increases toxicity of methotrexate. Inhibits phenytoin clearance. Potentiates warfarin and oral hypoglycaemics. Potentially Fatal: Co-admin with pyrimethamine causes megaloblastic anaemia. Enhancement of renal damage by ciclosporin.

Adverse Effects

Side effects of Sulphamethoxazole + Trimethoprim (Co-trimoxazole) : Allergic myocarditis, erythema multiforme, exfoliative dermatitis, angioedema, drug fever, chills, Henoch-Schoenlein purpura, serum sickness-like syndrome, generalised allergic reactions, generalised skin eruptions, photosensitivity, conjunctival and scleral inj, pruritus, urticaria, rash, periarteritis nodosa, SLE; elevated serum transaminase and bilirubin, pseudomembranous enterocolitis, pancreatitis, stomatitis, glossitis, nausea, emesis, abdominal pain, diarrhoea, anorexia; renal failure, interstitial nephritis, elevated BUN and serum creatinine, toxic nephrosis w/ oliguria and anuria; hyperkalaemia; aseptic meningitis, convulsions, peripheral neuritis, ataxia, vertigo, tinnitus, headache; hallucinations, depression, apathy, nervousness; dieresis, hypoglycaemia; arthralgia, myalgia; rhabdomyolysis; cough, shortness of breath, pulmonary infiltrates; weakness, fatigue, insomnia; QT prolongation, haemolysis, impaired phenylalanine metabolism. Potentially Fatal: Severe skin, hepatic and blood disorders, aplastic anaemia, hypersensitivity of the resp tract; Stevens-Johnson syndrome, toxic epidermal necrolysis; Clostridium difficile-associated diarrhoea; severe and symptomatic hyponatraemia.

Mechanism of Action

Co-trimoxazole exhibits the synergistic actions of its components (sulfamethoxazole and trimethoprim) by 10-fold. Sulfamethoxazole inhibits dihydrofolic acid formation from PABA, thus interfering with synthesis and growth of bacterial folic acid. Trimethoprim inhibits enzymes folic acid pathway, preventing the reaction of the dihydrolic acid to tetrahydrofolate. Co-trimoxazole possesses bactericidal effects against E coli, Klebsiella spp, Enterobacter spp, M morganii, P mirabilis, P vulgaris, H influenzae, Strep pneumoniae, Pneumocystis (carinii) jiroveci, Cyclospora spp.