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MEDICINE MONOGRAPH CODE: [8.25]-C67 ID: TIP-MED-000337

Sulfamethoxazole (Co-trimoxazole 1:5 FDC)

Active Ingredient / Scientific Identity: Sulfamethoxazole • Class: Synergistic Sequential Folate Pathway Inhibitor — DHFR + DHPS Blockade (Schedule H | NLEM 2022 | ICMR Access)

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THE INDIAN PHARMACIST — Educational Reference Sheet
Profile: Sulfamethoxazole (Co-trimoxazole 1:5 FDC) ([8.25]-C67 | ID: TIP-MED-000337) • Last Reviewed: 2026-11-10
Source URL: https://theindianpharmacist.com/medicine/8-25-c67-sulfamethoxazole-co-trimoxazole-1-5-fdc/
Generic / Entity NameSulfamethoxazole (Co-trimoxazole 1:5 FDC) ([8.25]-C67)
Verified Indian Brands / RefGeneric Compendial Entry (No Commercial Brand Claimed)
Pharmacological ClassSynergistic Sequential Folate Pathway Inhibitor — DHFR + DHPS Blockade (Schedule H | NLEM
Available Dosage FormsSingle-Strength (SS) Tablet: 80 mg TMP + 400 mg SMX (480 mg); Double-Strength (DS) Tablet: 160 mg TMP + 800 mg
Regulatory ClassificationSchedule H Prescription Drug (To be sold by retail on the prescription of a Registere
Key Warning & Review DateRenal: CrCl 15–30 mL/min: Halve dose (50% of standard dose); CrCl <15 mL/min: CONTRAINDICATED! Hepatic: Contraindicated in se
Reviewed: 2026-11-10
Safety Matrix:⚖️ Legal Status: Schedule H Prescription Drug (To be sold by retail o✔️ Standard Clinical Dispensing Precautions

1. Clinical & Scientific Overview

Sulfamethoxazole (Co-trimoxazole 1:5 FDC) (TIP-MED-000337, Reference Code [8.25]-C67) is classified under Antimicrobials — Antibacterial & Antibiotic Agents (Ch 08) as a Synergistic Sequential Folate Pathway Inhibitor — DHFR + DHPS Blockade (Schedule H | NLEM 2022 | ICMR Access). Within the Indian regulatory and compendial framework, it is governed under Schedule H Prescription Drug (To be sold by retail on the prescription of a Registered Medical Practitioner only — Drugs Rules 1945).

Verified Indian Market Examples / Compendial Status:
Co-indexed constituent under primary monograph [8.25] (Co-trimoxazole (Trimethoprim + Sulfamethoxazole — TMP-SMX)). Representative Indian Market Examples (Edition 2.7 Ch 08 [8.25], p. 105): Septran / Septran DS / Septran Paediatric (GSK), Bactrim DS (Abbott), Ciplin DS (Cipla) — Strengths & Dosage Forms: Single-Strength (SS) Tablet: 80 mg TMP + 400 mg SMX (480 mg); Double-Strength (DS) Tablet: 160 mg TMP + 800 mg SMX (960 mg); Paediatric Suspension: 40/200 mg per 5 mL
Co-indexed constituent under primary monograph [8.25] (Co-trimoxazole (Trimethoprim + Sulfamethoxazole — TMP-SMX)). Representative Indian Market Examples (Edition 2.7 Ch 08 [8.25], p. 105): Septran / Septran DS / Septran Paediatric (GSK), Bactrim DS (Abbott), Ciplin DS (Cipla) — Strengths & Dosage Forms: Single-Strength (SS) Tablet: 80 mg TMP + 400 mg SMX (480 mg); Double-Strength (DS) Tablet: 160 mg TMP + 800 mg SMX (960 mg); Paediatric Suspension: 40/200 mg per 5 mL
Dosage Forms & Available Strengths:
Single-Strength (SS) Tablet: 80 mg TMP + 400 mg SMX (480 mg); Double-Strength (DS) Tablet: 160 mg TMP + 800 mg SMX (960 mg); Paediatric Suspension: 40/200 mg per 5 mL
Routes: Oral / Parenteral / Topical per formulation

3. Mechanism of Action & Pharmacodynamics

Synergistic Sequential Folate Pathway Inhibitor — DHFR + DHPS Blockade (Schedule H | NLEM 2022 | ICMR Access) acting on target receptor/enzyme pathways in Antimicrobials — Antibacterial & Antibiotic Agents (Ch 08): clinical efficacy is mediated via Synergistic Sequential Folate Pathway Inhibitor — DHFR + DHPS Blockade (Schedule H | NLEM 2022 | ICMR Access) for Uncomplicated & complicated UTI / pyelonephritis, acute infectious diarrhoea/shigellosis, CA-MRSA skin infections, Pneumocystis jirovecii pneumonia (PCP) prophylaxis & treatment, toxoplasmosis, nocardiosis, and brucellosis.

4. Therapeutic Indications & Evidence-Supported Uses

  • Uncomplicated & complicated UTI / pyelonephritis, acute infectious diarrhoea/shigellosis, CA-MRSA skin infections, Pneumocystis jirovecii pneumonia (PCP) prophylaxis & treatment, toxoplasmosis, nocardiosis, and brucellosis

🇮🇳 Jurisdiction & Indication Note: Indications and schedules reflect Indian compendial and regulatory records (CDSCO / Indian Pharmacopoeia & NFI / NLEM 2022). Where international reference labels (US FDA DailyMed / NCBI StatPearls) are cited for pharmacokinetic or mechanistic parameters, international approvals do not automatically imply CDSCO approval in India.

5. Educational Dosage Context, Formulations & Administration

Educational Dosing & Regimen Summary: Standard Adult Infections (UTI/MRSA SSTI): 1 DS tablet (160/800 mg) PO BD for 3–14 days. PCP Prophylaxis: 1 SS (80/400 mg) OD or 1 DS (160/800 mg) OD / 3x weekly. PCP Treatment: 15–20 mg/kg/day (of TMP component) in 3–4 divided doses

Administration & Meal Timing: Take WITH food and a FULL GLASS (250 mL) OF WATER; maintain high daily fluid intake (>=2–2.5 L/day) to prevent sulfonamide crystalluria and stone formation | Morning & Evening (12-hourly BD for treatment; Once Daily for PCP prophylaxis)

6. Pharmacokinetics, Metabolism & Renal/Hepatic Adjustment

Absorption & Disposition:
Follows class pharmacokinetic profile detailed in parent monograph [8.25].
Metabolism & Biotransformation:
Renal: CrCl 15–30 mL/min: Halve dose (50% of standard dose); CrCl <15 mL/min: CONTRAINDICATED! Hepatic: Contraindicated in severe hepatic parenchymal damage
Elimination & Renal Adjustment:
Renal: CrCl 15–30 mL/min: Halve dose (50% of standard dose); CrCl <15 mL/min: CONTRAINDICATED! Hepatic: Contraindicated in severe hepatic parenchymal damage
Hepatic Impairment Considerations:
Renal: CrCl 15–30 mL/min: Halve dose (50% of standard dose); CrCl <15 mL/min: CONTRAINDICATED! Hepatic: Contraindicated in severe hepatic parenchymal damage

7. Contraindications, Precautions & High-Risk Warnings

Contraindications & Red-Flag Precautions:
  • CONTRAINDICATED in Sulfonamide ('Sulfa') or Trimethoprim allergy, history of SJS/TEN, megaloblastic folate-deficiency anaemia, G6PD deficiency (acute haemolysis!), 1st trimester of pregnancy and late 3rd trimester/infants <6 weeks (kernicterus!), severe CKD (CrCl <15 mL/min), and concomitant Methotrexate!

Key Clinical Precautions: Renal: CrCl 15–30 mL/min: Halve dose (50% of standard dose); CrCl <15 mL/min: CONTRAINDICATED! Hepatic: Contraindicated in severe hepatic parenchymal damage

8. Adverse Effects Profile

Common & Mechanism-Related Adverse Effects:
  • Nausea, vomiting, anorexia, maculopapular rash, pruritus, reversible 10–15% rise in serum creatinine (Trimethoprim blocks tubular creatinine secretion via OCT2 without reducing true GFR!)
  • Stevens–Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), DRESS syndrome, LIFE-THREATENING HYPERKALAEMIA (Trimethoprim acts identically to Amiloride on collecting duct ENaC channels!), agranulocytosis, aplastic anaemia, fulminant hepatic necrosis
Serious / Dose-Limiting Adverse Effects:

    9. Major Drug–Drug, Drug–Food & Drug–Herb Interactions

    • CRITICAL LETHAL INTERACTIONS: (1) METHOTREXATE + CO-TRIMOXAZOLE = Synergistic dual folate blockade causing RAPID FATAL PANCYTOPENIA & MUCOSITIS (NEVER co-prescribe!); (2) ACEi / ARBs / Spironolactone / Eplerenone + Co-trimoxazole in elderly/CKD = Severe Hyperkalaemia & Sudden Cardiac Death!; (3) Warfarin = Marked INR spike; (4) Sulfonylureas & Repaglinide = Severe hypoglycaemia; (5) Phenytoin = Phenytoin toxicity!

    10. Clinical Monitoring, Patient Counselling & Storage

    Clinical & Laboratory Monitoring: Monitor clinical parameters per parent monograph [8.25].

    Pharmacist Patient Counselling Points:

    • Patient Counselling Checklist: THREE VITAL COUNTER CHECKS: (1) Verify NO Sulfa allergy; (2) Confirm the patient is NOT taking Methotrexate (Folitrax) or Spironolactone/Telmisartan/Ramipril (or alert prescriber to check Potassium at Day 4!); (3) Drink 8–10 glasses of water daily and stop immediately at the first sign of any skin rash or mouth sores
    • Meal & Clock Timing Instruction: Take WITH food and a FULL GLASS (250 mL) OF WATER; maintain high daily fluid intake (>=2–2.5 L/day) to prevent sulfonamide crystalluria and stone formation (Morning & Evening (12-hourly BD for treatment; Once Daily for PCP prophylaxis))
    • Missed Dose Protocol: Take as soon as remembered with water; do not double dose
    • Geriatric Dispensing Pearl: High risk of sudden hyperkalaemic cardiac arrest (with ACEi/ARB/Spironolactone), Warfarin bleeding, and SJS/TEN in older adults (AGS Beers 2023)

    Storage, Stability & Dispensing Safeguards: Store below 25°C–30°C in original moisture- and light-resistant packaging out of reach of children. Available forms: Single-Strength (SS) Tablet: 80 mg TMP + 400 mg SMX (480 mg); Double-Strength (DS) Tablet: 160 mg TMP + 800 mg SMX (960 mg); Paediatric Suspension: 40/200 mg per 5 mL

    11. Visual Pharmacology & Mechanism Diagram (svg-v339-01-adme-12-step-journey)

    THE 12-STEP ORAL DRUG JOURNEY THROUGH THE HUMAN BODY (LADME) Note: IV bolus enters Step 6 directly (F = 100%); Sublingual & Transdermal routes bypass Step 4–5 Portal First-Pass Metabolism 1. Oral Administration • Tablet / Capsule swallowed • Gastric emptying to duodenum pH 1.5–3.5 (Stomach) 2. Disintegration & Dissolution • Tablet breaks into granules • API dissolves in GI fluid Noyes-Whitney Dissolution Rate 3. GI Epithelial Absorption • Crosses intestinal villi • Passive / Active / P-gp efflux Small Intestine (Large Surface Area) 4. Portal Circulation • Mesenteric veins → Portal vein • Delivers blood to liver sinusoids Pre-systemic Venous Conduit 5. First-Pass Metabolism • Gut & hepatic CYP450 extraction • High: GTN, Propranolol, Morphine Determines Bioavailability (F = f_a × (1-E_H)) 6. Systemic Circulation • Hepatic vein → IVC → Heart • Unbound vs Albumin-bound drug Only FREE drug is active 7–8. Tissue Distribution (Vd) • Capillary permeation to organs • Blood-Brain & Placental barriers Vd = Dose / C_0 (L or L/kg) 9. Target Site of Action • Receptors (GPCR, Ion channel) • Enzymes & Carrier Transporters Pharmacodynamic Effect (E_max, EC50) 10. Hepatic Biotransformation • Phase I (CYP450 Oxidation/Hydrolysis) • Phase II (Glucuronidation/Sulfation) Converts lipophilic drug → hydrophilic metabolite 11. Renal & Biliary Elimination • Nephron: Filtration + Secretion − Reabsorption • Biliary excretion & Enterohepatic recycling Total Clearance CL_tot = CL_renal + CL_hepatic 12. Excretion from the Body • Urine (Primary polar metabolite route) • Bile/Faeces, Expired Air, Sweat, Milk Elimination Half-Life t1/2 = (0.693 × Vd) / CL
    svg-v339-01-adme-12-step-journey — 8.1 Complete 12-Step Journey of an Orally Administered Drug (ADME): Figure 8.1: The 12-step physiological journey of a typical orally administered solid dosage form through Liberation, Absorption, Distribution, Metabolism, and Excretion (LADME). Note: Parenteral (IV), sublingual, and inhalational routes bypass gastrointestinal absorption and/or hepatic first-pass metabolism.

    12. Authoritative References, Regulatory Sources & Editorial Disclaimer

    Primary Compendial & Guideline Reference: Indian Pharmacopoeia (IP 2022) • NFI • CDSCO

    Official Verification Portals: Indian Pharmacopoeia Commission (IPC) & National Formulary of India (NFI) • Central Drugs Standard Control Organization (CDSCO) • Ministry of Health & Family Welfare — NLEM 2022 • NCBI Bookshelf / StatPearls Pharmacology Reference • DailyMed (US FDA Official Prescribing Reference)

    Last Medically & Pharmaceutically Reviewed: 2026-11-10 • Verification Status: VERIFIED_EDUCATIONAL_CONTENT

    Educational & Clinical Disclaimer: This reference profile is published solely for pharmacy education, academic study, and professional clinical reference. It does not substitute for patient-specific clinical judgement, qualified specialist oncology/medical supervision, or official CDSCO/IP prescribing information. Never self-medicate with prescription, Schedule H/H1/X, NDPS, or oncology medicines.

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    Educational Reference Notice: This printout from THE INDIAN PHARMACIST (https://theindianpharmacist.com/medicine/8-25-c67-sulfamethoxazole-co-trimoxazole-1-5-fdc/, Last Reviewed: 2026-11-10) is an educational reference sheet for students and healthcare learners. It is NOT an official prescribing guideline or patient-specific treatment order.