Pioglitazone + glimepiride

History of hypersensitivity reaction to sulfonamide derivatives. Established heart failure (NYHA class III or IV); active bladder cancer.

Patient with systolic dysfunction, oedema, risk factors for CHF; predisposition to hypoglycaemia (e.g. adrenal or pituitary insufficiency, deficient caloric intake; those who have undergone severe or prolonged exercise); history of bladder cancer; G6PD deficiency. Patient exposed to stress-related states (e.g. fever, trauma, infection, surgery). Patient taking strong CYP2C8 inhibitors (e.g. gemfibrozil). Debilitated or malnourished patient. Not intended for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis. Not recommended in patients with symptomatic heart failure. Treatment initiation in patients with clinical evidence of active liver disease or increased ALT >2.5 times ULN at baseline is not recommended. Renal and hepatic impairment. Elderly. Pregnancy and lactation. Patient Counselling This drug may cause impaired concentration or ability to react due to hypoglycaemia or low blood sugar, if affected, do not drive or operate machinery. Monitoring Parameters Obtain LFTs (e.g. ALT, AST, alkaline phosphatase, total bilirubin) before treatment initiation. Measure LFTs immediately in patients who have symptoms that may indicate liver injury (e.g. jaundice, dark urine, right upper abdominal discomfort, fatigue, anorexia). Monitor serum glucose, HbA_1c (at least twice yearly in patients with stable glycaemic control and are meeting treatment goals; quarterly in patients with change in therapy and whom treatment goals have not been met); monitor for weight gain. Perform regular ophthalmologic examinations. Assess for signs and symptoms of hypoglycaemia, heart failure (e.g. dyspnoea, oedema, rapid weight gain) and bladder cancer (e.g. urinary urgency, macroscopic haematuria, dysuria).

Significant: Hypoglycaemia, may cause or exacerbate CHF; oedema (including peripheral oedema); hypersensitivity reactions (e.g. anaphylaxis, angioedema, cutaneous eruptions, Stevens-Johnson syndrome), increased risk of urinary bladder cancer; weight gain; haemolytic anaemia (particularly in patients with G6PD deficiency); increased incidence of bone fractures (especially in women); decreased Hb/haematocrit. Rarely, new-onset or worsening macular oedema with decreased visual acuity. Blood and lymphatic system disorders: Anaemia, leucopenia, agranulocytosis, aplastic anaemia, pancytopenia, thrombocytopenia. Gastrointestinal disorders: Nausea, diarrhoea. Hepatobiliary disorders: Cholestasis, jaundice, hepatitis, hepatic porphyria. Metabolism and nutrition disorders: Hyponatraemia and SIADH. Musculoskeletal and connective tissue disorders: Limb pain. Nervous system disorders: Headache. Renal and urinary disorders: UTI. Respiratory, thoracic and mediastinal disorders: URTI. Skin and subcutaneous tissue disorders: Photosensitivity reactions, porphyria cutanea tarda.
Potentially Fatal: Increased CV mortality; severe hypoglycaemia; hepatic failure.

Pioglitazone: Increased exposure with strong CYP2C8 inhibitors (e.g. gemfibrozil). Decreased exposure with CYP2C8 inducers (e.g. rifampicin) and topiramate. Glimepiride: May increase hypoglycaemic effect with other oral antidiabetic agents, insulin, pramlintide, ACE inhibitors, disopyramide, quinolones, tetracyclines, clarithromycin, fibrates, H₂-receptor antagonists, propoxyphene, pentoxifylline, somatostatin analogues, anabolic steroids and androgens, fluconazole, miconazole, and drugs that are highly protein-bound (e.g. probenecid, fluoxetine, NSAIDs, salicylates, MAOIs, sulfonamides, coumarins, chloramphenicol). May decrease hypoglycaemic effect with atypical antipsychotic agents (e.g. olanzapine, clozapine), corticosteroids, danazol, glucagon, isoniazid, rifampicin, nicotinic acid, phenothiazines, protease inhibitors, somatropin, barbiturates, phenytoin, laxatives, diazoxide, thiazides and other diuretics, sympathomimetic agents (e.g. salbutamol, epinephrine, terbutaline), thyroid hormones, estrogens and oral contraceptives. May increase or decrease hypoglycaemic effect with clonidine, reserpine, and β-adrenergic blocking agents; signs of hypoglycaemia may be reduced or absent in patients receiving sympatholytic agents. Concurrent use with colesevelam may decrease the serum concentration of glimepiride.

Antidiabetic Agents

A10BG03 - pioglitazone ; Belongs to the class of thiazolidinediones. Used in the treatment of diabetes.
A10BB12 - glimepiride ; Belongs to the class of sulfonylureas. Used in the treatment of diabetes.