Wirkstoffe & Arzneimittelsicherheit

Nebenwirkungen · Competact

Competact 15 mg/850 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 9

HOS-115225 · Präparat HOS-094245

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 anaemia common Immune System Disorders hypersensitivity and allergic reactions1 not known not known Metabolism and nutrition disorders Vitamin B12 absorption decreased2 very rare very rare lactic acidosis very rare very rare Nervous system disorders hypo-aesthesia common common insomnia uncommon uncommon headache common taste disturbance common common Eye disorders visual disturbance3 common common

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Competact

Competact 15 mg/850 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 9–10

HOS-115226 · Präparat HOS-094245

9  Adverse reaction Frequency of adverse reactions Pioglitazone Metformin Competact macular oedema not known not known Gastrointestinal disorders4 abdominal pain very very common common diarrhoea very very common common flatulence uncommon loss of appetite very very common common nausea very very common common vomiting very very common common Hepatobiliary disorders hepatitis5 not known not known Skin and subcutaneous tissue disorders erythema very rare very rare pruritis very rare very rare urticaria very rare very rare Musculoskeletal and connective tissue disorders bone fracture6 common common arthralgia common Renal and urinary disorders haematuria common Reproductive system and breast disorders erectile dysfunction common General disorders and administration site conditions oedema7 common Investigations weight increased8 common common alanine aminotransferase increased9 not known not known liver function tests abnormal5 not known not known

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Competact

Competact 15 mg/850 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10

HOS-115227 · Präparat HOS-094245

Description of selected adverse reactions 1 Post-marketing reports of hypersensitivity reactions in patients treated with pioglitazone have been reported. These reactions include anaphylaxis, angioedema, and urticaria. 2 Long term treatment of metformin has been associated with a decrease of vitamin B12 absorption with decrease of serum levels. Consideration of such aetiology is recommended if a patient presents with megaloplastic anaemia. 3 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. 4 Gastrointestinal disorders occur most frequently during initiation of therapy and resolve spontaneously in most cases. 5 Isolated reports: liver function tests abnormalities or hepatitis resolving upon metformin discontinuation. 6 A pooled analysis was conducted of adverse reactions of bone fractures from randomised, comparator controlled, double blind clinical trials in over 8,100 patients in the pioglitazone-treated

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Competact

Competact 15 mg/850 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10–11

HOS-115228 · Präparat HOS-094245

10 groups and 7,400 in the comparator-treated groups of up to 3.5 years duration. A higher rate of fractures was observed in women taking pioglitazone (2.6%) versus comparator (1.7%). No increase in fracture rates was observed in men treated with pioglitazone (1.3%) versus comparator (1.5%). In the 3.5 year PROactive study, 44/870 (5.1%; 1.0 fractures per 100 patient years) of pioglitazone-treated female patients experienced fractures compared to 23/905 (2.5%; 0.5 fractures per 100 patient years) of female patients treated with comparator. The observed excess risk of fractures for women on pioglitazone in this study is therefore 0.5 fractures per 100 patient years of use. No increase in fracture rates was observed in men treated with pioglitazone (1.7%) versus comparator (2.1%). Post-marketing, bone fractures have been reported in both male and female patients (see section 4.4). 7 In active comparator controlled trials oedema was reported in 6.3% of patients treated with metformin and pioglitazone, whereas the addition of sulphonylurea to metformin treatment resulted in oedema in 2.2% of patients. The reports of oedema were generally mild to moderate and usually did not require discontinuation of treatment. 8 In active comparator controlled trials mean weight increase with pioglitazone given as monotherapy was 2-3 kg over one year. In combination trials pioglitazone added to metformin resulted in mean weight increase over one year of 1.5 kg. 9 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 or sulphonylurea comparator groups. Mean levels of liver enzymes decreased with treatment with pioglitazone.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Competact

Competact 15 mg/850 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-115229 · Präparat HOS-094245

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. In an outcome study of patients with pre-existing major macrovascular disease, the incidence of serious heart failure was 1.6% 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. In this study in patients receiving pioglitazone and insulin, a higher percentage of patients with heart failure was observed in patients aged ≥ 65 years compared with those less than 65 years (9.7% compared to 4.0%). In patients on insulin with no pioglitazone the incidence of heart failure was 8.2% in those ≥ 65 years compared to 4.0% 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 (see section 4.4).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Competact

Competact 15 mg/850 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-115230 · Präparat HOS-094245

Reporting of suspected adverse reactions

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Competact

Competact 15 mg/850 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-115231 · Präparat HOS-094245

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Gegenanzeigen · Tandemact

Tandemact 30 mg/2 mg tablets Tandemact 30 mg/4 mg tablets · Abschnitt 4.3 · PDF-Seite 3

HOS-115607 · Präparat HOS-094329

Tandemact is contraindicated in patients with:

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Gegenanzeigen · Tandemact

Tandemact 30 mg/2 mg tablets Tandemact 30 mg/4 mg tablets · Abschnitt 4.3 · PDF-Seite 3

HOS-115608 · Präparat HOS-094329

- 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)

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): creatinine (HOS-086273)

Wechselwirkungen · Tandemact

Tandemact 30 mg/2 mg tablets Tandemact 30 mg/4 mg tablets · Abschnitt 4.5 · PDF-Seite 6

HOS-115609 · Präparat HOS-094329

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).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Tandemact

Tandemact 30 mg/2 mg tablets Tandemact 30 mg/4 mg tablets · Abschnitt 4.5 · PDF-Seite 6

HOS-115610 · Präparat HOS-094329

Pioglitazone

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Tandemact

Tandemact 30 mg/2 mg tablets Tandemact 30 mg/4 mg tablets · Abschnitt 4.5 · PDF-Seite 6

HOS-115611 · Präparat HOS-094329

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).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): gemfibrozil (HOS-088403)

Wechselwirkungen · Tandemact

Tandemact 30 mg/2 mg tablets Tandemact 30 mg/4 mg tablets · Abschnitt 4.5 · PDF-Seite 6

HOS-115613 · Präparat HOS-094329

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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): digoxin (HOS-086172) phenprocoumon (HOS-091031) calcium (HOS-085615) warfarin (HOS-085950) metformin (HOS-091032)

Wechselwirkungen · Tandemact

Tandemact 30 mg/2 mg tablets Tandemact 30 mg/4 mg tablets · Abschnitt 4.5 · PDF-Seite 6–7

HOS-115616 · Präparat HOS-094329

6 Glimepiride

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Tandemact

Tandemact 30 mg/2 mg tablets Tandemact 30 mg/4 mg tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-115617 · Präparat HOS-094329

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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Tandemact

Tandemact 30 mg/2 mg tablets Tandemact 30 mg/4 mg tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-115618 · Präparat HOS-094329

Based on the experience with glimepiride and with other sulphonylureas the following interactions have to be mentioned.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Tandemact

Tandemact 30 mg/2 mg tablets Tandemact 30 mg/4 mg tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-115619 · Präparat HOS-094329

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:

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Tandemact

Tandemact 30 mg/2 mg tablets Tandemact 30 mg/4 mg tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-115620 · Präparat HOS-094329

phenylbutazone, azapropazone and oxyfenbutazone insulin and oral antidiabetic products metformin salicylates and p-amino-salicylic acid anabolic steroids and male sex hormones chloramphenicol clarithromycin coumarin anticoagulants disopyramide fenfluramine fibrates angiotensin-converting enzyme (ACE) inhibitors fluoxetine allopurinol sympatholytics cyclo-, tro- and iphosphamides sulphinpyrazone certain long-acting sulphonamides tetracyclines MAO-inhibitors quinolone antibiotics probenecid miconazole pentoxyfylline (high dose parenteral) tritoqualine fluconazole

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): allopurinol (HOS-089178) fenfluramine (HOS-115627) coumarin (HOS-088372) salicylic acid (HOS-088803) disopyramide (HOS-085595) fluconazole (HOS-087945) clarithromycin (HOS-084517) probenecid (HOS-085208) tritoqualine (HOS-115631) fluoxetine (HOS-085946) chloramphenicol (HOS-115623) phenylbutazone (HOS-110030) metformin (HOS-091032) miconazole (HOS-115630)

Wechselwirkungen · Tandemact

Tandemact 30 mg/2 mg tablets Tandemact 30 mg/4 mg tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-115633 · Präparat HOS-094329

Weakening of the blood-glucose-lowering effect and, thus raised blood glucose levels may occur when one of the following active substances is taken, for example:

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): glucose (HOS-088412)

Wechselwirkungen · Tandemact

Tandemact 30 mg/2 mg tablets Tandemact 30 mg/4 mg tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-115634 · Präparat HOS-094329

oestrogens and progestagens, saluretics, thiazide diuretics, thyroid stimulating agents, glucocorticoids, phenothiazine derivatives, chlorpromazine, adrenaline and sympathicomimetics, nicotinic acid (high doses) and nicotinic acid derivatives, laxatives (long-term use), phenytoin, diazoxide, glucagon, barbiturates and rifampicin. acetozolamide

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): diazoxide (HOS-088588) chlorpromazine (HOS-087796) phenytoin (HOS-084531) glucagon (HOS-088589)