Clinical Pharmacology Details


Metformin Hydrochloride


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Indications & Dose:

Diabetes mellitus, type 2: polycystie ovary syndrome



Adult



• Initially 500mg three times daily with breakfast or 850 twice daily or 850mg twice daily with or after meals. Adjust dose after 10-15 days according to response; max. 3g daily
• Combination therapy: If after 4 wk and a 2 gm daily dose of metformin, there is an inadequate response, sulfonylurea should be added; if at maximum doses of a sulfonylurea and metformin the patient still has an inadequate response, both agents should be stopped, and insulin should be started
• Adding metformin to insulin therapy: Continue current insulin dose; initial recommended dosage of metformin is 250-500 mg daily; increased by 250-500 mg/day at intervals of 1 wk or more; max dose is 2,000 mg/day; fasting plasma glucose concentration below 120 mg/dL call for decreasing insulin dose by 10%25% and closer monitoring
• Transferring metformin to sulfonylurea: (except chlorpropamide to metformin), no transition period is necessary; if transferring from chlorpropamide, careful monitoring for 2 wk due to an increased risk of hypoglycemia
• Geriatric dosing: Conservative initial and maintenance doses due to decreased renal function; dosage adjustments made carefully and conservatively; maximal doses should not be used


NOTE: Lower initiation doses (i.e., 250 mg qd) with gradual titration (i.e., 250 mg q3-5 days) may attente GI adverse effect

Contraindications:

Congestive heart failure requiring drug therapy, acute or chronic metabolic acidosis, including ketoacidosis, renal impairment (e.g., serum creatinine > 1.5 mg/dL in males; 1.4 mg/dL in females); during (temporarily) radiology studies using iodinated contrast media failure.

Side Effects:

CNS: Headache


GI: Abdominal bloating, anorexia, diarrhea, flatulence, metallic taste, nausea, vomiting


HFME: Megaloblastic anemia (impaired vitamin B12 absorption)


METAB: Hypoglycemia (rare); lactic acidosis (diarrhea; severe muscle pain, cramping; shallow and fast breathing, unusual tiredness and weakness, unusual sleepiness)


SKIN: Dermatitis, rash

Cautions:

Precautions:

Hypoxemia, dehydration, hepatic disease, severe congestive failure, fever, trauma, infection, megaloblastic anemia, thyroid disease, excessive alcohol intake; during and after surgical procedures

Interaction:

Drugs


Clmetidine: Increased metformin AUC 50%, peak concentrations 81%, and decreased renal clearance 27%, increasing the risk of lactic acidosis


Monomine oxidase (MAO) inhibitors: Stimulate insulin secretion via B-adrenergic stimulation; excessive and prolonged hypoglycemia may, occur in some individuals.

Warnings:

Adverse Effects:

Lactations:

PREGNANCY AND LACTATION: Safety not established.


BREAST-FEEDING: Discontinue nursing or drugs

Special Precautions:

Counselling:

Side Effects Or Adverse Reactions:

Patient And Carer Advice: