PIOGLITAZONE TORRENT

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 system organ class, adverse reactions are presented in order of decreasing incidence followed by decreasing seriousness. Frequency of adverse reactions of pioglitazone by treatment regimen Combination Adverse reaction Monotherapy With metformin With sulphonylurea With metformin and sulphonylurea 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 disturbance 2 common common uncommon Macular oedema not known not known not known not known not known Ear and labyrinth disorders Vertigo uncommon Cardiac disorders Heart failure 3 common Respiratory, thoracic and mediastinal disorders Dyspnoea common Gastrointestinal disorders Flatulence uncommon common Skin and subcutaneous tissue disorders Sweating uncommon Musculoskeletal and connective tissue disorders Fracture bone 4 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 increased 6 common common common common common Blood creatine phospho-kinase increased common Increased lactic dehydro-genase uncommon Alanine aminotransferase increased 7 not known not known not known not known not known Description of selected adverse reactions 1 Postmarketing reports of hypersensitivity reactions in patients treated with pioglitazone have been reported.

These reactions include anaphylaxis, angioedema, and urticaria. 2 Visual disturbance has been reported mainly early in treatment and is related to changes in blood glucose due to temporary alteration in the turgidity and refractive index of the lens as seen with other hypoglycaemic treatments.

3 In controlled clinical trials the incidence of reports of heart failure with pioglitazone treatment was the same as in placebo, metformin and sulphonylurea treatment groups, but was increased when used in combination therapy with insulin.

6% higher with pioglitazone than with placebo, when added to therapy that included insulin. However, this did not lead to an increase in mortality in this study. 0%). 0% in patients less than 65 years. Heart failure has been reported with marketing use of pioglitazone, and more frequently when pioglitazone was used in combination with insulin or in patients with a history of cardiac failure.

5 years duration. 7%). 5%). 5%) of female patients treated with comparator. 1%). 4) 5 Oedema was reported in 6–9% of patients treated with pioglitazone over one year in controlled clinical trials. The oedema rates for comparator groups (sulphonylurea, metformin) were 2–5%.

The reports of oedema were generally mild to moderate and usually did not require discontinuation of treatment. 6 In active comparator controlled trials mean weight increase with pioglitazone given as monotherapy was 2–3 kg over one year.

This is similar to that seen in a sulphonylurea active comparator group. 8 kg. 0 kg. 7 In clinical trials with pioglitazone the incidence of elevations of ALT greater than three times the upper limit of normal was equal to placebo but less than that seen in metformin […]

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 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 nonsteroidal 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.

5 years. This study showed an increase in reports of heart failure; however this did not lead to an increase in mortality in this study. Elderly Combination use with insulin should be considered with caution in the elderly because of increased risk of serious heart failure.

In the light of age-related risks (especially bladder cancer, fractures and heart failure), the balance of benefits and risks should be considered carefully both before and during treatment in the elderly. 029). 02 %) in control groups.

Epidemiological studies have also suggested a small increased risk of bladder cancer in diabetic patients treated with pioglitazone, although not all studies identified a statistically significant increased risk. Risk factors for bladder cancer should be assessed before initiating pioglitazone treatment (risks include age, smoking history, exposure to some occupational or chemotherapy agents e.

g. cyclophosphamide or prior radiation treatment in the pelvic region). Any macroscopic haematuria should be investigated before starting pioglitazone therapy. Patients should be advised to promptly seek the attention of the physician if macroscopic haematuria or other symptoms such as dysuria or urinary urgency develop during treatment.

8). It is recommended, therefore, that patients treated with pioglitazone undergo periodic monitoring of liver enzymes. Liver enzymes should be checked prior to the initiation of therapy with pioglitazone in all patients. 5 X upper limit of normal) or with any other evidence of liver disease.

Following initiation of therapy with pioglitazone, it is recommended that liver enzymes be monitored periodically based on clinical judgement. If ALT levels are increased to 3 X upper limit of normal during pioglitazone therapy, liver enzyme levels should be reassessed as soon as possible.

If ALT levels remain >3 X the upper limit of normal, therapy should be discontinued. If any patient develops symptoms suggesting hepatic dysfunction, which may include unexplained nausea, vomiting, abdominal pain, fatigue, anorexia and/or dark urine, liver enzymes should be checked.

The decision whether to continue the patient on therapy with pioglitazone should be guided by clinical judgement pending laboratory evaluations. If jaundice is observed, drug therapy should be discontinued. Weight gain In clinical trials with pioglitazone there was evidence of dose related weight gain, which may be due to fat accumulation and in some cases associated with fluid retention.

In some cases weight increase may be a symptom of cardiac failure; therefore weight should be closely […]

Pioglitazone is contraindicated in patients with: - hypersensitivity to the active substance or to any of the excipients - 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