Wirkstoffe & Arzneimittelsicherheit

Nebenwirkungen · Tandemact

Tandemact 30 mg/2 mg tablets Tandemact 30 mg/4 mg tablets · Abschnitt 4.8 · PDF-Seite 9

HOS-115645 · Präparat HOS-094329

Tabulated list of adverse reactions

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

Nebenwirkungen · Tandemact

Tandemact 30 mg/2 mg tablets Tandemact 30 mg/4 mg tablets · Abschnitt 4.8 · PDF-Seite 9

HOS-115646 · Präparat HOS-094329

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.

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

Nebenwirkungen · Tandemact

Tandemact 30 mg/2 mg tablets Tandemact 30 mg/4 mg tablets · Abschnitt 4.8 · PDF-Seite 9

HOS-115647 · Präparat HOS-094329

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 uncommon appetite increased uncommon Nervous system disorders dizziness common hypo-aesthesia common common headache uncommon insomnia uncommon uncommon Eye disorders visual disturbance4 common uncommon macular oedema not known not known Ear and labyrinth disorders vertigo uncommon Gastrointestinal disorders5 flatulence common vomiting very rare very rare diarrhoea very rare very rare nausea very rare very rare abdominal pain very rare very rare abdominal pressure very rare very rare

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

Nebenwirkungen · Tandemact

Tandemact 30 mg/2 mg tablets Tandemact 30 mg/4 mg tablets · Abschnitt 4.8 · PDF-Seite 9–10

HOS-115648 · Präparat HOS-094329

9  Adverse reaction Frequency of adverse reactions Pioglitazone Glimepiride Tandemact feeling of fullness in the stomach very rare very rare Hepatobiliary disorders6 hepatitis very rare very rare impairment of liver function (with cholestasis and very rare very rare jaundice) Skin and subcutaneous tissue disorders sweating uncommon hypersensitivity to light very rare very rare urticaria2 not known not known itching2 not known not known rash2 not known not known Musculoskeletal and connective tissue disorders bone fracture7 common common Renal and urinary disorders glycosuria uncommon proteinuria uncommon General disorders and administration site conditions oedema8 common fatigue uncommon Investigations weight increased9 common common common increased lactic dehydrogenase uncommon decrease in sodium serum concentrations very rare very rare alanine aminotransferase increase10 not known not known

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

Nebenwirkungen · Tandemact

Tandemact 30 mg/2 mg tablets Tandemact 30 mg/4 mg tablets · Abschnitt 4.8 · PDF-Seite 10

HOS-115649 · Präparat HOS-094329

Description of selected adverse reactions 1 Moderate to severe thrombocytopenia, leucopenia, erythrocytopenia, granulocytopenia, agranulocytosis, haemolytic anaemia and pancyto-penia may occur. These are in general reversible upon discontinuation of treatment. 2 In very rare cases mild hypersensitivity reactions may develop into serious reactions with dyspnoea, fall in blood pressure and sometimes shock. Hypersensitivity reactions of the skin may occur as itching, rash, and urticaria. Cross allergenicity with sulphonylureas, sulphonamides or related substances is possible. 3 Postmarketing reports of hypersensitivity reactions in patients treated with pioglitazone have been reported. These reactions include anaphylaxis, angioedema, and urticaria. 4 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 medicinal products. 5 Gastro-intestinal complaints are very rare and seldom lead to discontinuation of therapy. 6 Elevation of liver enzymes may occur. In very rare cases, impairment of liver function (e.g. with cholestasis and jaundice) may develop, as well as hepatitis which may progress to liver failure. 7 A pooled analysis was conducted of adverse event reports of bone fractures from randomised, comparator controlled, double blind clinical trials in over 8,100 patients in the pioglitazone-treated 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%).

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

Nebenwirkungen · Tandemact

Tandemact 30 mg/2 mg tablets Tandemact 30 mg/4 mg tablets · Abschnitt 4.8 · PDF-Seite 10–11

HOS-115650 · Präparat HOS-094329

10 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). 8 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. 9 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. In combination trials pioglitazone added to a sulphonylurea resulted in a mean weight increase over one year of 2.8 kg. 10 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 · Tandemact

Tandemact 30 mg/2 mg tablets Tandemact 30 mg/4 mg tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-115651 · Präparat HOS-094329

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 in 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 · Tandemact

Tandemact 30 mg/2 mg tablets Tandemact 30 mg/4 mg tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-115652 · Präparat HOS-094329

Reporting of suspected adverse reactions 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.

Wechselwirkungen · Trajenta

Trajenta 5 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 4

HOS-124321 · Präparat HOS-095839

Sulphonylureas: co-administration of multiple oral doses of 5 mg linagliptin and a single oral dose of 1.75 mg glibenclamide (glyburide) resulted in clinically not relevant reduction of 14% of both AUC and Cmax of glibenclamide. Because glibenclamide is primarily metabolised by CYP2C9, these data also support the conclusion that linagliptin is not a CYP2C9 inhibitor. Clinically meaningful interactions would not be expected with other sulphonylureas (e.g., glipizide, tolbutamide, and glimepiride) which, like glibenclamide, are primarily eliminated by CYP2C9.

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): glipizide (HOS-109460) glimepiride (HOS-112373) glyburide (HOS-109273) tolbutamide (HOS-086568)

Wechselwirkungen · Jentadueto

Jentadueto 2.5 mg/850 mg film-coated tablets Jentadueto 2.5 mg/1 000 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-214069 · Präparat HOS-155256

Sulphonylureas: Co-administration of multiple oral doses of 5 mg linagliptin and a single oral dose of 1.75 mg glibenclamide (glyburide) resulted in clinically not relevant reduction of 14% of both AUC and Cmax of glibenclamide. Because glibenclamide is primarily metabolised by CYP2C9, these data also support the conclusion that linagliptin is not a CYP2C9 inhibitor. Clinically meaningful interactions would not be expected with other sulphonylureas (e.g., glipizide, tolbutamide, and glimepiride) which, like glibenclamide, are primarily eliminated by CYP2C9.

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): glipizide (HOS-109460) glimepiride (HOS-112373) glyburide (HOS-109273) tolbutamide (HOS-086568)

Wechselwirkungen · Forxiga

Forxiga 5 mg film-coated tablets Forxiga 10 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-125342 · Präparat HOS-096051

Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered by metformin, pioglitazone, sitagliptin, glimepiride, voglibose, hydrochlorothiazide, bumetanide, valsartan, or simvastatin.

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): glimepiride (HOS-112373) dapagliflozin (HOS-125333) hydrochlorothiazide (HOS-086937) simvastatin (HOS-086158) pioglitazone (HOS-089663) bumetanide (HOS-125088) valsartan (HOS-088810) sitagliptin (HOS-117222) metformin (HOS-091032)

Wechselwirkungen · Forxiga

Forxiga 5 mg film-coated tablets Forxiga 10 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-125349 · Präparat HOS-096051

In interaction studies conducted in healthy subjects, using mainly a single-dose design, dapagliflozin did not alter the pharmacokinetics of metformin, pioglitazone, sitagliptin, glimepiride, hydrochlorothiazide, bumetanide, valsartan, digoxin (a P-gp substrate) or warfarin (S-warfarin, a CYP2C9 substrate), or the anticoagulatory effects of warfarin as measured by INR. Combination of a single dose of dapagliflozin 20 mg and simvastatin (a CYP3A4 substrate) resulted in a 19% increase in AUC of simvastatin and 31% increase in AUC of simvastatin acid. The increase in simvastatin and simvastatin acid exposures are not considered clinically relevant.

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): glimepiride (HOS-112373) dapagliflozin (HOS-125333) hydrochlorothiazide (HOS-086937) simvastatin (HOS-086158) digoxin (HOS-086172) pioglitazone (HOS-089663) bumetanide (HOS-125088) valsartan (HOS-088810) sitagliptin (HOS-117222) warfarin (HOS-085950) metformin (HOS-091032)

Wechselwirkungen · Kalydeco

Kalydeco 75 mg film-coated tablets Kalydeco 150 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 12

HOS-126439 · Präparat HOS-096263

Ivacaftor may inhibit CYP2C9. Therefore, monitoring of the international normalised ratio (INR) is recommended during co-administration of warfarin with ivacaftor. Other medicinal products for which exposure may be increased include glimepiride and glipizide; these medicinal products should be used with caution.

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): glipizide (HOS-109460) glimepiride (HOS-112373) warfarin (HOS-085950)

Wechselwirkungen · Kalydeco

Kalydeco 13.4 mg granules in sachet Kalydeco 25 mg granules in sachet Kalydeco 50 mg granules in sachet Kalydeco 59.5 mg granules in sachet Kalydeco 75 mg granules in sachet · Abschnitt 4.5 · PDF-Seite 42

HOS-126508 · Präparat HOS-096263

Ivacaftor may inhibit CYP2C9. Therefore, monitoring of the international normalised ratio (INR) is recommended during co-administration of warfarin with ivacaftor. Other medicinal products for which exposure may be increased include glimepiride and glipizide; these medicinal products should be used with caution.

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): glipizide (HOS-109460) glimepiride (HOS-112373) warfarin (HOS-085950)

Wechselwirkungen · Xigduo

Xigduo 5 mg/850 mg film-coated tablets Xigduo 5 mg/1,000 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-128327 · Präparat HOS-096549

Effect of other medicinal products on dapagliflozin Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered by pioglitazone, sitagliptin, glimepiride, voglibose, hydrochlorothiazide, bumetanide, valsartan, or simvastatin.

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): glimepiride (HOS-112373) dapagliflozin (HOS-125333) hydrochlorothiazide (HOS-086937) simvastatin (HOS-086158) pioglitazone (HOS-089663) bumetanide (HOS-125088) valsartan (HOS-088810) sitagliptin (HOS-117222)

Wechselwirkungen · Xigduo

Xigduo 5 mg/850 mg film-coated tablets Xigduo 5 mg/1,000 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-128335 · Präparat HOS-096549

In interaction studies conducted in healthy subjects, using mainly a single-dose design, dapagliflozin did not alter the pharmacokinetics of pioglitazone, sitagliptin, glimepiride, hydrochlorothiazide, bumetanide, valsartan, digoxin (a P-gp substrate) or warfarin (S-warfarin, a CYP2C9 substrate), or the anti-coagulatory effects of warfarin as measured by INR. Combination of a single dose of dapagliflozin 20 mg and simvastatin (a CYP3A4 substrate) resulted in a 19% increase in AUC of simvastatin and 31% increase in AUC of simvastatin acid. The increase in simvastatin and simvastatin acid exposures are not considered clinically relevant.

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): glimepiride (HOS-112373) dapagliflozin (HOS-125333) hydrochlorothiazide (HOS-086937) simvastatin (HOS-086158) digoxin (HOS-086172) pioglitazone (HOS-089663) bumetanide (HOS-125088) valsartan (HOS-088810) sitagliptin (HOS-117222) warfarin (HOS-085950)

Wechselwirkungen · Jardiance

Jardiance 10 mg film-coated tablets Jardiance 25 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-128454 · Präparat HOS-096571

Interaction studies suggest that the pharmacokinetics of empagliflozin were not influenced by co- administration with metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, warfarin, verapamil, ramipril, simvastatin, torasemide and hydrochlorothiazide.

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): ramipril (HOS-089057) glimepiride (HOS-112373) hydrochlorothiazide (HOS-086937) simvastatin (HOS-086158) pioglitazone (HOS-089663) linagliptin (HOS-124309) sitagliptin (HOS-117222) warfarin (HOS-085950) metformin (HOS-091032) verapamil (HOS-090602)

Wechselwirkungen · Jardiance

Jardiance 10 mg film-coated tablets Jardiance 25 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-128462 · Präparat HOS-096571

Interaction studies conducted in healthy volunteers suggest that empagliflozin had no clinically relevant effect on the pharmacokinetics of metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, simvastatin, warfarin, ramipril, digoxin, diuretics and oral contraceptives.

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): ramipril (HOS-089057) glimepiride (HOS-112373) simvastatin (HOS-086158) digoxin (HOS-086172) pioglitazone (HOS-089663) linagliptin (HOS-124309) sitagliptin (HOS-117222) warfarin (HOS-085950) metformin (HOS-091032)

Wechselwirkungen · Synjardy

Synjardy 5 mg/850 mg film-coated tablets Synjardy 5 mg/1 000 mg film-coated tablets Synjardy 12.5 mg/850 mg film-coated tablets Synjardy 12.5 mg/1 000 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-131178 · Präparat HOS-097021

Interaction studies suggest that the pharmacokinetics of empagliflozin were not influenced by co-administration with metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, warfarin, verapamil, ramipril, simvastatin, torasemide and hydrochlorothiazide.

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): ramipril (HOS-089057) glimepiride (HOS-112373) hydrochlorothiazide (HOS-086937) simvastatin (HOS-086158) pioglitazone (HOS-089663) linagliptin (HOS-124309) sitagliptin (HOS-117222) warfarin (HOS-085950) verapamil (HOS-090602)

Wechselwirkungen · Synjardy

Synjardy 5 mg/850 mg film-coated tablets Synjardy 5 mg/1 000 mg film-coated tablets Synjardy 12.5 mg/850 mg film-coated tablets Synjardy 12.5 mg/1 000 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-131183 · Präparat HOS-097021

Interaction studies conducted in healthy volunteers suggest that empagliflozin had no clinically relevant effect on the pharmacokinetics of metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, simvastatin, warfarin, ramipril, digoxin, diuretics and oral contraceptives.

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): ramipril (HOS-089057) glimepiride (HOS-112373) simvastatin (HOS-086158) digoxin (HOS-086172) pioglitazone (HOS-089663) linagliptin (HOS-124309) sitagliptin (HOS-117222) warfarin (HOS-085950)