1. Metformin Hydrochloride

7. Pharmacokinetics (Absorption, Distribution, Metabolism, Excretion): Absorption, distribution, metabolism, and excretion follow class pharmacokinetic profile; verify patient renal/hepatic function.

16a. Renal Considerations: KDIGO 2024 & CDSCO Renal Thresholds: eGFR >= 60 mL/min/1.73m²: Full dose (monitor renal function annually); eGFR 45–59: Continue, monitor every 3–6 months; eGFR 30–44: Halve maximum dose (max 1000 mg/day) and do NOT initiate new therapy; eGFR < 30 mL/min/1.73m²: STRICTLY CONTRAINDICATED due to lactic acidosis risk.

16b. Hepatic Considerations: Contraindicated in acute or decompensated hepatic insufficiency, severe tissue hypoxia, sepsis, or acute alcohol intoxication (impaired hepatic lactate clearance).

• Gastrointestinal disturbance: metallic taste, nausea, abdominal cramping, diarrhoea (mitigated by taking WITH meals and switching to SR/PR formulation)
• Vitamin B12 deficiency with long-term therapy (>2–3 years; monitor CBC and serum B12 especially in peripheral neuropathy)
• Rare but potentially fatal Metformin-Associated Lactic Acidosis (MALA: pH < 7.35, lactate > 5 mmol/L)

• Iodinated Intravenous Radiocontrast Media: Hold Metformin prior to or at the time of contrast administration in patients with eGFR 30–60 mL/min/1.73m² or intra-arterial contrast; re-evaluate eGFR at 48 hours before restarting.
• Cationic OCT2/MATE1 Inhibitors (Dolutegravir, Cimetidine, Ranolazine, Trimethoprim): Reduce renal tubular secretion of Metformin; cap Metformin at 1000 mg/day when co-administered with Dolutegravir (TLD regimen).
• Alcohol: Potentiates hyperlactataemia and hypoglycaemia risk.

15. Use in Special Populations (Pregnancy, Lactation, Paediatrics, Geriatrics): Evaluate maternal-foetal benefit-risk ratio, paediatric mg/kg ceiling, and geriatric renal function prior to prescribing.

17. Clinical & Laboratory Monitoring: Monitor clinical response, baseline renal/hepatic parameters, and relevant serum biomarkers.

• Swallow tablets WITH or immediately after meals (evening meal for once-daily SR tablets) to prevent stomach upset.
• Do NOT crush, chew, or break Sustained-Release (SR/XR) tablets; note that an inert ghost matrix shell may appear in stool.
• Follow the 'SAD-MANS' Sick-Day Protocol: temporarily pause Metformin during severe vomiting, diarrhoea, high fever, or dehydration and seek medical review.

Storage & Dispensing Notes: Store in moisture-resistant blister packs below 30°C. Verify IR vs SR/PR release modifier and check multi-ingredient FDC strengths (e.g., Glimepiride 1 mg/2 mg + Metformin 500 mg/1000 mg SR).