ACTOZONE 30MG 10 TAB.

Composition:Each tablet contains Pioglitazone as ( hydrochloride ) 30 or 45 mg Indications And Usage:Actozone® is indicated in the treatment of type 2 diabetes mellitus: as monotherapy in adult patients (particularly overweight patients) inadequately controlled by diet and exercise for whom metformin is inappropriate because of contraindications or intolerance.

As dual oral therapy in combination with metformin, in adult patients (particularly overweight patients) with insufficient glycaemic control despite maximal tolerated dose of monotherapy with metformin a sulphonylurea, only in adult patients who show intolerance to metformin or for whom metformin is contraindicated, with insufficient glycaemic control despite maximal tolerated dose of monotherapy with a sulphonylurea.

As triple oral therapy in combination with metformin and a sulphonylurea, in adult patients (particularly overweight patients) with insufficient glycaemic control despite dual oral therapy.

Actozone® is also indicated for combination with insulin in type 2 diabetes mellitus adult patients with insufficient glycaemic control on insulin for whom metformin is inappropriate because of contraindications or intolerance.

Posology and method of administration Posology: Pioglitazone 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.

Special population: Elderly: No dose adjustment is necessary for elderly patients .

Renal impairment: No dose adjustment is necessary in patients with impaired renal function (creatinine clearance > 4 ml/min).

No information is available from dialysed patients therefore pioglitazone should not be used in such patients.

Hepatic impairment: Pioglitazone should not be used in patients with hepatic impairment .

Paediatric population : The safety and efficacy of Actozone® in children and adolescents under 18 years of age have not been established.

No data are available.

Contraindications:Actozone® 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 Ito IV) hepatic impairment diabetic ketoacidosis.

Drug Interactions:Interaction studies have shown that pioglitazone has no relevant effect on either the pharmacokinetics or pharmacodynamics of digoxin, warfarin, phenprocoumon and metformin.

Co-administration of pioglitazone with sulphonylureas does not appear to affect the pharmacokinetics of the sulphonylurea.

Studies in man suggest no induction of the main inducible cytochrome P450, 1A, 2C8/9 and 3A4.

In vitro studies have shown no inhibition of any subtype of cytochrome P450 Interactions with substances metabolised by these enzymes, e.g.

oral contraceptives, cyclosporin, calcium channel blockers, and HMGCoA reductase inhibitors are not to be expected.

Co-administration of pioglitazone with gemfibrozil (an inhibitor of cytochrome P450 2C8) is reported to result in a 3-fold increase in AUC of pioglitazone.

Since there is a potential for an increase in dose-related adverse events, a decrease in the dose of pioglitazone may be needed when gemfibrozil is concomitantly administered.

Close monitoring of glycaemic control should be considered .

Co-administration of pioglitazone with rifampicin (an inducer of cytochrome P450 2C8) is reported to result in a 54% decrease in AUC of pioglitazone.

The pioglitazone dose may need to be increased when rifampicin is concomitantly administered.

Close monitoring of glycaemic control should be considered .

How Supplied:Strips of 10 tablets ( 30-45 mg ) in packs of one, two, three strips.

Precautions:4.1.Fluid retention and cardiac failure: Pioglitazone can cause fluid retention.

which may exacerbate or precipitate heart failure.

Pioglitazone should be discontinued if any deterioration in cardiac status occurs.

4.2.Monitoring of liver function: Liver enzyme should be checked prior to therapy with pioglitazone in all patients.

Therapy with pioglitazone should not be initiated in patients with increased baseline liver enzyme levels (ALT > 2.5 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.

4.3.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.

4.4.Haematology: There was a small reduction in mean haemoglobin (4% relative reduction) and haematocrit (4.1% relative reduction) during therapy with pioglitazone, consistent with haemodilution.

4.5.Hypoglycaemia: As a consequence of increased insulin sensitivity, patients receiving pioglitazone in dual or triple oral therapy with a sulphonylurea or in dual therapy with insulin may be at risk for dose-related hypoglycaemia, and a reduction in the dose of the sulphonylurea or insulin may be necessary.

4.6.Eye disorders: Post-marketing reports of new-onset or worsening diabetic macular oedema with decreased visual acuity have been reported with thiazolidinediones, including pioglitazone.

4.7.Others: An increased incidence in bone fractures in women was seen in a pooled analysis of adverse reactions of bone fracture from randomised, controlled, double blind clinical trials in over 8100 pioglitazone and 7400 comparator treated patients.

Effects on ability to drive and use machines: Actozone® has no or negligible effect on the ability to drive and use machines.

However patients who experience visual disturbance should be cautious when driving or using machines.

Recommendations For prescribers: Do not use pioglitazone in patients with active bladder cancer.

Use pioglitazone with patients with a prior history of bladder cancer.

The benefits of glycemic control versus unknown risks for cancer recurrence with pioglitazone should be considered in patients with a prior history of bladder cancer.

Counsel patients to report any signs or symptoms of blood in urine, urinary urgency, Pain, on urination, or back or abdominal pain, as these may be due to bladder cancer.

Encourage patients to read the Medication Guide they get with their pioglitazone medicine.

Report adverse events involving pioglitazone medicines.

Pregnancy & Lactation: Pregnancy: Pioglitazone should not be used in pregnancy.

Breastfeeding: Pioglitazone should not be administered to breast-feeding women.

Adverse Effects:Adverse reactions reported in excess (> 0.5%) of placebo and as more than an isolated case in patients receiving pioglitazone in double-blind studies are listed below as Med DRA preferred term by system organ class and absolute frequency.

Frequencies are defined as: very common (≥1/10); common (≥1/100 to < 1/10); uncommon (≥1/1000 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.

adverse reactions are presented in order of decreasing incidence and seriousness.

7.1.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.

7.2.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.