Tandemact · 4.3 Contraindications · 1

HOS-094336 · has-adverse-reaction-information · PDF-Seite 9

Summary of the safety profile Clinical trials have been conducted with co-administered pioglitazone and glimepiride (see section 5.1). Hypoglycaemic reactions mostly occur immediately due to the sulphonylurea component of Tandemact. Symptoms can almost always be promptly controlled by immediate intake of carbohydrates (sugar). This is a serious reaction which may occur uncommonly (≥ 1/1,000 to < 1/100) (see section 4.4). Moderate to severe thrombocytopenia, leucopenia, erythrocytopenia, granulocytopenia, agranulocytosis, haemolytic anaemia and pancytopenia may occur rarely (≥ 1/10,000 to < 1/1,000) (see section 4.4). Other reactions such as bone fracture, weight increase and oedema may occur commonly (≥ 1/100 to < 1/10) (see section 4.4). Tabulated list of adverse reactions Adverse reactions reported in double-blind studies and post marketing experience 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. Adverse reaction Frequency of adverse reactions Pioglitazone Glimepiride Tandemact Infections and infestations upper respiratory tract infection common common sinusitis uncommon uncommon Neoplasms benign, malignant and unspecified (including cysts and polyps) bladder cancer uncommon uncommon Blood and lymphatic system disorders changes in haematology1 rare rare Immune system disorders allergic shock2 very rare very rare allergic vasculitis2 very rare very rare hypersensitivity and allergic reactions3 not known not known Metabolism and nutrition disorders hypoglycaemia

Auszug; vollständigen Abschnitt im Original lesen.

HOS-094332 · has-contraindication-information · PDF-Seite 3

Tandemact is contraindicated in patients with: - Hypersensitivity to the active substances or to any of the excipients listed in section 6.1, or other sulphonylureas or sulphonamides - Cardiac failure or history of cardiac failure (NYHA stages I to IV) - Current bladder cancer or a history of bladder cancer - Uninvestigated macroscopic haematuria - Hepatic impairment - Type 1 diabetes mellitus - Diabetic coma - Diabetic ketoacidosis - Severe renal function disorders (creatinine clearance < 30 ml/min) - Pregnancy - Breast-feeding (see section 4.6)

HOS-094331 · has-indication-information · PDF-Seite 2

Tandemact is indicated as second line treatment of adult patients with type 2 diabetes mellitus who show intolerance to metformin or for whom metformin is contraindicated and who are already treated with a combination of pioglitazone and glimepiride. After initiation of therapy with pioglitazone, patients should be reviewed after 3 to 6 months to assess adequacy of response to treatment (e.g. reduction in HbA1c). In patients who fail to show an adequate response, pioglitazone should be discontinued. In light of potential risks with prolonged therapy, prescribers should confirm at subsequent routine reviews that the benefit of pioglitazone is maintained (see section 4.4).

HOS-094334 · has-interaction-information · PDF-Seite 6

There have been no formal interaction studies for Tandemact, however, the concomitant use of the active substances in patients in clinical use has not resulted in any unexpected interactions. The following statements reflect the information available on the individual active substances (pioglitazone and glimepiride). Pioglitazone 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. A decrease in the dose of pioglitazone may be needed when gemfibrozil is concomitantly administered. Close monitoring of glycaemic control should be considered (see section 4.4). 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 (see section 4.4). 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. 6 Glimepiride If glimepiride is taken simultaneously with certain other medicinal products, both undesired increases and decreases in the hypoglycaemic action of glimepiride can occur. For this reason, other medicinal products should only be taken with Tandemact with the knowledge (or at the prescription) of the doctor. Based on the experience with glimepiride and with other sulphonylureas the following interactions have to be mentioned. Potentiation of the blood-glucose-lowering effect and, thus, in some instances hypoglycaemia may occur when one of the following active substances is taken, for example: phenylbutazone, azapropazone and oxyfenbutazone insulin and oral antidiabetic products metformin salicylates and p-amino-salicylic acid anabolic steroids and male sex hormones chlorampheni

Auszug; vollständigen Abschnitt im Original lesen.

HOS-094335 · has-pregnancy-information · PDF-Seite 8

Women of childbearing potential / Contraception in males and females Tandemact is not recommended in women of childbearing potential not using contraception. If a patient wishes to become pregnant, treatment with Tandemact should be discontinued. Pregnancy Risk related to pioglitazone There are no adequate data from the use of pioglitazone in pregnant women. Studies of pioglitazone in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Risk related to glimepiride There are no adequate data from the use of glimepiride in pregnant women. Animal studies have shown reproductive toxicity which was most likely related to the pharmacological action (hypoglycaemia) of glimepiride. Tandemact is contraindicated during pregnancy (see section 4.3). If a pregnancy occurs, treatment with Tandemact should be discontinued. Breast-feeding Sulphonylurea-derivatives like glimepiride pass into the breast milk. Pioglitazone has been shown to be present in the milk of lactating rats. It is not known whether pioglitazone is secreted in human milk. Tandemact is contra-indicated during breast-feeding (see section 4.3). Fertility In animal fertility studies with pioglitazone, there was no effect on copulation, impregnation or fertility index.

HOS-094333 · has-warning-information · PDF-Seite 3

There is no clinical trial experience of other oral anti-hyperglycaemic medicinal products added to treatment with Tandemact or concomitantly administered glimepiride and pioglitazone. Hypoglycaemia When meals are taken at irregular hours or skipped altogether, treatment with Tandemact may lead to hypoglycaemia due to the sulphonylurea component. Symptoms can almost always be promptly controlled by immediate intake of carbohydrates (sugar). Artificial sweeteners have no effect. It is known from other sulphonylureas that, despite initially successful countermeasures, hypoglycaemia may recur. Severe hypoglycaemia or prolonged hypoglycaemia, only temporarily 3 controlled by the usual amounts of sugar, require immediate medical treatment and occasionally hospitalisation. Treatment with Tandemact requires regular monitoring of glycaemic control. Fluid retention and cardiac failure Pioglitazone can cause fluid retention, which may exacerbate or precipitate heart failure. When treating patients who have at least one risk factor for development of congestive heart failure (e.g. prior myocardial infarction or symptomatic coronary artery disease or the elderly), physicians should start with the lowest available dose of pioglitazone 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. 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. Tandemact should be discontinued if any deterioration in cardiac state 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. Pioglitazone or placebo was added to existing antidiabetic and cardiovascular therapy for up to 3.5 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

Auszug; vollständigen Abschnitt im Original lesen.