Editrim

Approved Indications:

• Urinary Tract Infections (UTIs): Acute and chronic infections caused by susceptible strains of E. coli, Klebsiella, Proteus, Enterobacter.
• Respiratory Tract Infections:
• Acute exacerbations of chronic bronchitis
• Community-acquired pneumonia (CAP), especially Pneumocystis jirovecii pneumonia (PCP)
• Gastrointestinal Infections:
• Traveler's diarrhea and Shigellosis
• Salmonella enteritis or enteric fever
• Ear, Nose, Throat (ENT) Infections: Otitis media, especially in children
• Skin & Soft Tissue Infections: Mild to moderate infections caused by MRSA (Methicillin-resistant Staphylococcus aureus)
• Prophylaxis and treatment of Pneumocystis jirovecii pneumonia (PCP) in HIV/AIDS patients
• Prophylaxis and treatment of Toxoplasmosis (especially in immunocompromised patients)
• Nocardiosis
• Brucellosis (used as part of a multidrug regimen)

Off-label / Clinically Accepted Uses:

• Whipple’s disease (caused by Tropheryma whipplei)
• Melioidosis (caused by Burkholderia pseudomallei)
• Stenotrophomonas maltophilia infections
• Acne vulgaris (in resistant cases or nodulocystic acne, off-label)

General Guidelines:

• Route: Oral or intravenous (IV)
• Ratio: Standard formulation contains Sulphamethoxazole 400 mg + Trimethoprim 80 mg (5:1 ratio)

Adults:

• Usual dose: 800 mg SMX + 160 mg TMP (double-strength tablet) every 12 hours
• Severe infections: May increase to 20 mg/kg/day TMP component divided every 6-8 hours
• IV use: 8-20 mg/kg/day TMP divided every 6-8 hours (infused over 60–90 minutes)

Pediatrics:

• Children (≥2 months): 40 mg/kg/day SMX + 8 mg/kg/day TMP, divided every 12 hours
• Infants with PCP: 20 mg/kg/day TMP divided every 6 hours

Elderly:

• Dose adjustment based on renal function is strongly advised due to increased risk of toxicity.

Renal Impairment:

• CrCl 15–30 mL/min: Half of the normal dose
• CrCl <15 mL/min: Avoid or use with extreme caution

Hepatic Impairment:

• No specific dose adjustment; monitor liver function regularly.

PCP Prophylaxis (HIV Patients):

• Adults: 800/160 mg once daily or 3 times weekly
• Children: 150 mg/m² TMP once daily or on 3 alternate days/week

Sulphamethoxazole and Trimethoprim act synergistically to inhibit sequential steps in the folate synthesis pathway of bacteria. Sulphamethoxazole is a sulfonamide that inhibits dihydropteroate synthase, preventing the formation of dihydrofolic acid. Trimethoprim inhibits dihydrofolate reductase, blocking the conversion of dihydrofolic acid to tetrahydrofolic acid. This dual blockade results in effective bacteriostatic or bactericidal action (depending on concentration and pathogen), impairing bacterial DNA, RNA, and protein synthesis.

• Absorption: Rapid and nearly complete oral absorption
• Bioavailability: ~90–100% (oral)
• Distribution: Widely distributed into tissues and body fluids, including CSF, lungs, middle ear, and placenta
• Protein Binding: SMX ~66%, TMP ~45%
• Metabolism:
• SMX: Hepatic (primarily acetylation and glucuronidation)
• TMP: Partially hepatic
• Half-life:
• SMX: ~10 hours
• TMP: ~8–10 hours
• Excretion: Primarily renal (both unchanged and as metabolites)
• Onset of action: Within 1–4 hours
• Steady-state achieved: In 2–3 days

• Pregnancy:
• Category D (US FDA): Risk of fetal folate deficiency and teratogenicity, particularly in the first trimester
• Use only if clearly needed and benefits outweigh risks
• Lactation:
• Both components are excreted in breast milk
• May cause kernicterus in premature or jaundiced neonates; avoid in breastfeeding mothers of infants <2 months
• Generally compatible in older infants, with caution

• Primary Class: Antibacterial agent
• Sub-class: Sulfonamide + dihydrofolate reductase inhibitor combination (antimetabolite synergy)
• ATC Code: J01EE01

• Known hypersensitivity to sulfonamides, trimethoprim, or any excipients
• Severe renal impairment (if dose adjustment not possible)
• Severe hepatic insufficiency
• Megaloblastic anemia due to folate deficiency
• Infants <2 months of age
• Pregnancy (especially 1st trimester and near term)
• Breastfeeding (in neonates or premature infants)
• History of drug-induced immune thrombocytopenia or Stevens-Johnson syndrome from sulfonamides

• Risk of serious skin reactions: Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN)
• Hematologic monitoring: Regular CBC required due to risk of anemia, leukopenia, or thrombocytopenia
• Renal toxicity: Monitor creatinine, especially in prolonged therapy
• Hepatotoxicity: Monitor LFTs
• Hyperkalemia: Especially in elderly, those on ACE inhibitors or potassium-sparing diuretics
• Folate deficiency: May require folinic acid supplementation
• Risk of crystalluria: Ensure adequate hydration
• G6PD deficiency: Use with caution due to risk of hemolysis

Common:

• Gastrointestinal: Nausea, vomiting, diarrhea, anorexia
• Skin: Rash, photosensitivity
• CNS: Headache, dizziness

Serious:

• Hematologic: Aplastic anemia, agranulocytosis, thrombocytopenia
• Renal: Interstitial nephritis, crystalluria
• Hepatic: Hepatitis, liver failure (rare)
• Dermatologic: SJS, TEN, DRESS syndrome
• Metabolic: Hyperkalemia, hyponatremia
• Allergic reactions: Anaphylaxis, angioedema

• ACE inhibitors, ARBs, spironolactone: ↑ risk of hyperkalemia
• Warfarin: Potentiation of anticoagulant effect via CYP2C9 inhibition → ↑ INR/bleeding risk
• Phenytoin: Trimethoprim inhibits metabolism → ↑ phenytoin toxicity
• Methotrexate: Additive antifolate effects → ↑ hematologic toxicity
• Sulfonylureas: ↑ hypoglycemia risk
• Cyclosporine: May ↑ nephrotoxicity
• Oral contraceptives: May reduce effectiveness (rare)
• Enzyme system: CYP2C9 inhibition is significant

• HIV Guidelines: Co-trimoxazole remains a first-line agent for PCP prophylaxis and treatment in WHO and CDC guidelines
• Antibiotic stewardship: Increasing emphasis on rational use due to emerging resistance, especially in E. coli
• EMA Update: Ongoing pharmacovigilance for severe cutaneous adverse reactions in European populations
• New Dosing Considerations (2023): Individualized weight-based high-dose therapy for PCP in severely immunocompromised patients

• Oral Tablets/Suspension:
• Store below 25°C
• Protect from light and moisture
• Shake oral suspension well before use
• IV Formulation:
• Store at 20°C–25°C
• Protect from freezing
• Discard unused diluted solution after 6 hours (room temp) or 24 hours (refrigerated)
• Use only clear, particulate-free solution