Glipizide + Metformin Hydrochloride

Indications

Glipizide + Metformin Hydrochloride is used for: Type 2 DM

Adult Dose

Type 2 Diabetes Mellitus Initial treatment: start at 2.5 mg/250 mg (glipizide/metformin) PO qDay with food If fasting plasma glucose = 280-320 mg/dL: 2.5/500 mg PO q12hr May adjust daily dose in increments of 1 tab every 2 wk. Max: Glipizide 10 mg and metformin 2,000 mg daily. Type 2 DM Inadequately Controlled on Sulfonylurea &/or Metformin 2nd-line treatment: Start at 2.5/500 mg or 5/500 mg PO q12hr with food May adjust daily dose in increments of not more than 5 mg/500 mg. Max: Glipizide 20 mg and metformin 2,000 mg daily. Hepatic impairment: Contraindicated.

Child Dose

Renal Dose

Renal impairment: Serum creatinine (SCr) >1.5 mg/dL (males) or >1.4 mg/dL (females) Obtain eGFR before starting metformin eGFR <30 mL/min/1.73 m²: Contraindicated eGFR 30-45 mL/min/1.73 m²: Not recommended to initiate treatment Monitor eGFR at least annually or more often for those at risk for renal impairment (eg, elderly) If eGFR falls below 45mL/min/1.73 m² while taking metformin, risks and benefits of continuing therapy should be evaluated If eGFR falls below 30 mL/min/1.73 m²: while taking metformin, discontinue the drug

Administration

Should be taken with food.

Contra Indications

Hypersensitivity. Type 2 diabetes mellitus; ketoacidosis; severe renal or hepatic insufficiency, diabetic coma, cardiac failure, recent MI, CHF. IDDM; severe infection; acute or chronic metabolic acidosis with or without coma; stress, trauma; severe impairment of thyroid function; dehydration, acute or chronic alcoholism. Pregnancy, lactation.

Precautions

Hypoglycaemia, stress, elderly. Thyroid impairment, monitor blood-glucose conc and renal function regularly. Lactation: enters breast milk; not recommended

Pregnancy-Lactation

Pregnancy Category: C Lactation: enters breast milk; not recommended

Interactions

Glipizide: Decreased effect with beta-blockers, cholestyramine, hydantoins, thiazide diuretics and urinary alkalinizers. Metformin: Additive effect with sulphonylureas. Antagonistic effects with diuretics, corticosteroids, phenothiazines, thyroid products, oestrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, Ca channel blockers and isoniazid. Potentially Fatal: Glipizide: Increased glipizide levels and effects with fluconazole, gemfibrozil, ketoconazole, NSAIDs, pioglitazone and sulfonamides. Increased hypoglycaemic effects with H2 antagonists, anticoagulants, androgens, cimetidine, salicylates, tricyclic antidepressants, probenecid, MAOIs, methyldopa, digitalis glycosides and urinary acidifiers. Metformin: Lactic acidosis with alcohol and potentiation of hypoglycaemic effect. Cimetidine and furosemide may increase plasma-metformin levels. Drugs eliminated via renal tubular secretion may increase metformin levels.

Adverse Effects

Side effects of Glipizide + Metformin Hydrochloride : Glipizide: GI upsets, diarrhoea, nausea; allergic skin reactions, leucopaenia, thrombocytopaenia, agranulocytosis, hyponatraemia; jaundice; haemolytic anaemia, pancytopaenia. Metformin: Anorexia, nausea, vomiting, diarrhoea, wt loss, flatulence, occasional metallic taste; weakness; hypoglycaemia; rash, malabsorption of Vitamin Potentially Fatal: Glipizide: Hypoglycaemia in presence of renal or hepatic damage and alcohol. Metformin: Lactic acidosis in presence of renal failure and alcoholism.

Mechanism of Action

Glipizide stimulates insulin release from pancreatic beta-cells and reduces gluconeogenesis in liver cells. It also increases insulin sensitivity at target sites. Metformin decreases hepatic gluconeogenesis, decreases intestinal absorption of glucose and improves insulin sensitivity (increases peripheral glucose uptake and utilisation).