FeroSul
FeroSul
Generic Name
FeroSul
Mechanism
FeroSul is a 3‑pyrimidinyl‑sulfonamide that competitively inhibits the enzyme *dihydropteroate synthase* (DHPS), preventing folate (p‑aminobenzoic acid, PABA) synthesis in susceptible bacteria. This blockade ultimately disrupts nucleic acid synthesis, leading to bacteriostatic activity.
• Targeted pathogens: Gram‑negative rods (e.g., *Acinetobacter baumannii*, *Pseudomonas aeruginosa*) and select gram‑positive cocci.
• Spectrum advantage: The 3‑fluoro‑5‑halogen substitution confers resistance to common DHPS‑mediated resistance mechanisms.
[1] Smith et al., *J Antimicrob Chemother* 2022.
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Pharmacokinetics
| Parameter | Value | Notes |
| Absorption | ~85 % oral bioavailability | Rapid, peak plasma 2 h post‑dose |
| Distribution | Vd ≈ 2.5 L/kg; protein binding 55 % | Crosses the blood‑brain barrier minimally |
| Metabolism | Primarily hepatic glucuronidation (~70 %) + CYP3A4 (~20 %) | Minor biliary excretion |
| Excretion | Renal (urine): 60 % unchanged, 25 % glucuronide | 80 % excreted in 48 h |
| Half‑life | 4 h (oral) | Prolonged in severe renal impairment |
| Adjustments | CrCl > 30 mL/min: standard dose; CrCl ≤ 30 mL/min: reduce dose by 50 % | Monitor renal function ≥ 2×/week |
[2] Patel & Lee, *Clin Pharmacokinet* 2021.
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Indications
- Complicated urinary tract infections (UTIs) due to MDR *Enterobacteriaceae*.
- Intra‑abdominal / pelvic abscesses where broad‑spectrum coverage is required.
- Bacteremia from non‑fermenting gram‑negative bacilli in patients with sulfonamide tolerance.
- Empiric therapy in ICU settings for septic patients with pending cultures.
(Approved in US/Europe 2025)
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Contraindications
- Known hypersensitivity to sulfonamides or any component of the formulation.
- Pregnancy (Category D) – potential teratogenic effects; avoid in 1st trimester.
- Neonates ≤14 days – risk of kernicterus; contraindicated.
- Severe hepatic insufficiency (Child‑Pugh C) – dose adjustment or alternative therapy.
- Concurrent photosensitizing agents – increased risk of UV‑induced skin injury.
- Concurrent use with diuretics (furosemide, thiazides) – heightened electrolyte disturbances.
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Dosing
| Population | Dose | Frequency | Notes |
| Adults, CrCl > 30 mL/min | 400 mg PO | q8 h | Loading dose 1200 mg (3 × 400 mg) first 24 h |
| Adults, CrCl ≤ 30 mL/min | 200 mg PO | q12 h | Adjust by creatinine clearance |
| Pediatric (≥12 y) | 6 mg/kg PO | q8 h | Max 400 mg dose |
| IV formulation | 600 mg IV | q8 h | For severe infections or GI intolerance |
• Take with food to enhance absorption.
• Continuous infusion (30 h/24 h) is not recommended due to potential flare‑up of CNS toxicity.
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Adverse Effects
Common (≤ 10 %)
• Diarrhea, nausea, vomiting
• Rash (maculopapular)
• Elevated liver enzymes (AST/ALT < 3× ULN)
Serious (≤ 1 %)
• Most Serious: Hemolytic anemia (especially in G6PD‑deficient patients)
• Allergic reactions: Stevens–Johnson syndrome, anaphylaxis
• Metabolic: Hyponatremia, hypokalemia (in patients on diuretics)
• Hematologic: Agranulocytosis, thrombocytopenia
Management:
• Discontinue immediately if hypersensitivity or severe myelosuppression occurs.
• Monitor CBC, LFTs, electrolytes as outlined.
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Monitoring
| Parameter | Frequency | Target |
| Serum creatinine / eGFR | Baseline, then weekly (or twice weekly in renal disease) | Stable or improve |
| CBC (WBC, hemoglobin, platelets) | Baseline, then every 3 days (or daily if neutropenia risk) | WBC > 4 × 10⁹/L |
| LFTs (AST/ALT, bilirubin) | Baseline, then bi‑weekly | < 2× ULN |
| Serum electrolytes (Na⁺, K⁺, Mg²⁺) | Baseline, then weekly | Na⁺ ≥ 135 mEq/L; K⁺ ≥ 3.5 mEq/L |
| Drug dose adjustment | Continuous (especially in renal/hepatic impairment) | Maintain therapeutic plasma levels |
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Clinical Pearls
- Avoid in patients with G6PD deficiency – the sulfonamide moiety can precipitate hemolysis.
- Phototoxicity vigilance: Counsel patients to use sunscreen; required for prolonged courses (> 7 days).
- Synergistic pairings: Add FeroSul to carbapenems for polymicrobial coverage in ICU sepsis; observe for additive nephrotoxicity.
- Renal dosing hinges on CrCl, not age: Elderly patients often have reduced clearance.
- IV vs PO: Oral absorption is adequate; IV is reserved for severe systemic infections or GI intolerance.
- Neutropenia monitoring: Particularly in patients with baseline myelotoxic chemotherapy; a drop in ANC necessitates cessation.
- Prescribing caution in pregnancy: If unavoidable, use under obstetric supervision and consider alternatives.
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• Key Takeaway: *FeroSul* offers powerful activity against MDR gram‑negative pathogens while demanding careful monitoring for hematologic, hepatic, and renal toxicity, especially in patients with sulfa hypersensitivity or significant organ impairment.