PIOGLITAZONE MYLAN

Posology Pioglitazone treatment may be initiated at 15 mg or 30 mg once daily. The dose may be increased in increments up to 45 mg once daily. In combination with insulin, the current insulin dose can be continued upon initiation of pioglitazone therapy.

If patients report hypoglycaemia, the dose of insulin should be decreased. 2). Physicians should start treatment with the lowest available dose and increase the dose gradually, particularly when pioglitazone is used in combination with insulin (see section

5 %) of placebo and as more than an isolated case in patients receiving pioglitazone in double-blind studies are listed below as MedDRA preferred term by system organ class and absolute frequency. Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data).

Within each frequency grouping, undesirable effects are presented in order of decreasing incidence and seriousness. Frequency of adverse reactions of pioglitazone by treatment regimen Combination Adverse reaction Mono- therapy with metformin with sulfonylurea with metformin and sulfonylurea with insulin Infections and infestations upper respiratory tract infection common common common common common bronchitis common sinusitis uncommon uncommon uncommon uncommon uncommon Neoplasms benign, malignant and unspecified (including cysts and polyps) bladder cancer uncommon uncommon uncommon uncommon uncommon Blood and lymphatic system disorders anaemia common Immune System Disorders Hypersensitivity and allergic reactions1 not known not known not known not known not known Metabolism and nutrition disorders hypo-glycaemia uncommon very common common appetite increased uncommon Nervous system disorders hypo-aesthesia common common common common common headache common uncommon dizziness common insomnia uncommon uncommon uncommon uncommon uncommon Eye disorders visual disturbance2 common common uncommon macular oedema not known not known not known not known not known Ear and labyrinth disorders vertigo uncommon Cardiac disorders heart failure3 common Respiratory, thoracic and mediastinal disorders dyspnoea common Gastrointestinal disorders flatulence uncommon common Skin and subcutaneous tissue disorders sweating uncommon Frequency of adverse reactions of pioglitazone by treatment regimen Combination Adverse reaction Mono- therapy With metformin With sulfonylurea With metformin and sulfonylurea With insulin Musculoskeletal and connective tissue disorders fracture bone4 common common common common common arthralgia common common common back pain common Renal and urinary disorders haematuria common glycosuria uncommon proteinuria uncommon Reproductive system and breast disorders erectile dysfunction common General disorders and administration site conditions oedema5 very common fatigue uncommon Investigations weight increased6 common common common common common blood creatine phospho-kinase increased common increased lactic dehydro-genase uncommon alanine aminotransferase increased7 not known not known not known not known not known Description of selected adverse reactions 1 Post-marketing reports of hypersensitivity reactions in patients treated with pioglitazone have been reported.

4 Fluid retention and cardiac failure). 2). No information is available from dialysed patients therefore pioglitazone should not be used in such patients. 4). Paediatric population The safety and efficacy of pioglitazone in children and adolescents under 18 years of age have not been established.

No data are available. Method of administration For oral use. Pioglitazone tablets are taken orally once daily with or without food. Tablets should be swallowed with a glass of water. 4 Special warnings and precautions for use Fluid retention and cardiac failure: Pioglitazone can cause fluid retention, which may exacerbate or precipitate heart failure.

g. prior myocardial infarction or symptomatic coronary artery disease or the elderly), physicians should start with the lowest available dose and increase the dose gradually. Patients should be observed for signs and symptoms of heart failure, weight gain or oedema particularly those with reduced cardiac reserve.

There have been post-marketing cases of cardiac failure reported when pioglitazone was used in combination with insulin or in patients with a history of cardiac failure. Patients should be observed for signs and symptoms of heart failure, weight gain and oedema when pioglitazone is used in combination with insulin.

Since insulin and pioglitazone are both associated with fluid retention, concomitant administration may increase the risk of oedema. Post marketing cases of peripheral oedema and cardiac failure have also been reported in patients with concomitant use of pioglitazone and non-steroidal anti-inflammatory drugs, including selective COX-2 inhibitors.

Pioglitazone should be discontinued if any deterioration in cardiac status occurs. A cardiovascular outcome study of pioglitazone has been performed in patients under 75 years with type 2 diabetes mellitus and pre-existing major macrovascular disease.

1 - Cardiac failure or history of cardiac failure (NYHA stages I to IV) - Hepatic impairment - Diabetic ketoacidosis - Current bladder cancer or a history of bladder cancer - Uninvestigated macroscopic haematuria