Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Xigduo

Xigduo 5 mg/850 mg film-coated tablets Xigduo 5 mg/1,000 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-128343 · Präparat HOS-096549

Some medicinal products can adversely affect renal function which may increase the risk of lactic acidosis, e.g. NSAIDs, including selective cyclo-oxygenase (COX) II inhibitors, ACE inhibitors, angiotensin II receptor antagonists and diuretics, especially loop diuretics. When starting or using such products in combination with metformin, close monitoring of renal function is necessary.

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): angiotensin II (HOS-085480)

Wechselwirkungen · Xigduo

Xigduo 5 mg/850 mg film-coated tablets Xigduo 5 mg/1,000 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-128344 · Präparat HOS-096549

Insulin and insulin secretagogues Insulin and insulin secretagogues, such as sulphonylureas, cause hypoglycaemia. Therefore, a lower dose of insulin or an insulin secretagogue may be required to reduce the risk of hypoglycaemia when used in combination with metformin (see sections 4.2 and 4.8).

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Nebenwirkungen · Xigduo

Xigduo 5 mg/850 mg film-coated tablets Xigduo 5 mg/1,000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10

HOS-128345 · Präparat HOS-096549

Xigduo has been demonstrated to be bioequivalent with coadministered dapagliflozin and metformin (see section 5.2). There have been no therapeutic clinical trials conducted with Xigduo tablets.

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Nebenwirkungen · Xigduo

Xigduo 5 mg/850 mg film-coated tablets Xigduo 5 mg/1,000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10

HOS-128346 · Präparat HOS-096549

Dapagliflozin plus metformin Summary of the safety profile In an analysis of 5 placebo-controlled dapagliflozin add-on to metformin studies, the safety results were similar to that of the pre-specified pooled analysis of 13 placebo-controlled dapagliflozin studies (see Dapagliflozin, Summary of the safety profile below). No additional adverse reactions were identified for the dapagliflozin plus metformin group compared with those reported for the individual components. In the separate dapagliflozin add-on to metformin pooled analysis, 623 subjects were treated with dapagliflozin 10 mg as add-on to metformin and 523 were treated with placebo plus metformin.

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Nebenwirkungen · Xigduo

Xigduo 5 mg/850 mg film-coated tablets Xigduo 5 mg/1,000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10

HOS-128347 · Präparat HOS-096549

Dapagliflozin Summary of the safety profile In the clinical studies in type 2 diabetes, more than 15,000 patients have been treated with dapagliflozin.

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Nebenwirkungen · Xigduo

Xigduo 5 mg/850 mg film-coated tablets Xigduo 5 mg/1,000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10

HOS-128348 · Präparat HOS-096549

The primary assessment of safety and tolerability was conducted in a pre-specified pooled analysis of 13 short-term (up to 24 weeks) placebo-controlled studies with 2,360 subjects treated with dapagliflozin 10 mg and 2,295 treated with placebo.

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Nebenwirkungen · Xigduo

Xigduo 5 mg/850 mg film-coated tablets Xigduo 5 mg/1,000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10

HOS-128349 · Präparat HOS-096549

In the dapagliflozin cardiovascular outcomes study (DECLARE, see section 5.1), 8,574 patients received dapagliflozin 10 mg and 8,569 received placebo for a median exposure time of 48 months. In total, there were 30,623 patient-years of exposure to dapagliflozin.

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Nebenwirkungen · Xigduo

Xigduo 5 mg/850 mg film-coated tablets Xigduo 5 mg/1,000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10

HOS-128350 · Präparat HOS-096549

The most frequently reported adverse reactions across the clinical studies were genital infections.

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Nebenwirkungen · Xigduo

Xigduo 5 mg/850 mg film-coated tablets Xigduo 5 mg/1,000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10

HOS-128351 · Präparat HOS-096549

Tabulated list of adverse reactions The following adverse reactions have been identified in the placebo-controlled dapagliflozin plus metformin clinical studies, dapagliflozin clinical studies and metformin clinical studies and post-marketing experience. None were found to be dose-related. Adverse reactions listed below are classified according to frequency and system organ class. Frequency categories are defined according to the following convention: 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), and not known (cannot be estimated from the available data).

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Nebenwirkungen · Xigduo

Xigduo 5 mg/850 mg film-coated tablets Xigduo 5 mg/1,000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10–11

HOS-128352 · Präparat HOS-096549

10 Table 2. Adverse reactions in dapagliflozin and metformin immediate-release clinical trial and post-marketing dataa System organ Very common Common Uncommon Rare Very rare class Infections and Vulvovaginitis, Fungal Necrotising infestations balanitis and infection** fasciitis of related genital the perineum infections*,b,c (Fournier’s Urinary tract gangrene)b,j infection*,b,d Metabolism and Hypoglycaemia Vitamin B12 Volume Diabetic Lactic nutrition (when used decrease/ depletionb,e ketoacidosisb,j,k acidosis disorders with SU or deficiencyj,§ Thirst** insulin)b Nervous system Taste disorders disturbance§ Dizziness

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Nebenwirkungen · Xigduo

Xigduo 5 mg/850 mg film-coated tablets Xigduo 5 mg/1,000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-128353 · Präparat HOS-096549

Gastrointestinal Gastro- Constipation** disorders intestinal Dry mouth** symptomsh,§ Hepatobiliary Liver disorders function disorders§ Hepatitis§ Skin and Rashl Urticaria§ subcutaneous Erythema§ tissue disorders Pruritus§ Musculo- Back pain* skeletal and connective tissue disorders Renal and Dysuria Nocturia** Tubulo- urinary Polyuria*,f interstitial disorders nephritis Reproductive Vulvovaginal system and pruritus** breast disorders Pruritus genital** Investigations Haematocrit Blood increasedg creatinine Creatinine increased renal clearance during initial decreased treatment**,b during initial Blood urea treatmentb increased** Dyslipidaemiai Weight decreased** a The table shows adverse reactions identified from up to 24-week (short-term) data regardless of glycaemic rescue, except those marked with § (see below). b See corresponding subsection below for additional information. c Vulvovaginitis, balanitis and related genital infections includes, e.g. the predefined preferred terms: vulvovaginal mycotic infection, vaginal infection, balanitis, genital infection fungal, vulvovaginal candidiasis, vulvovaginitis, balanitis candida, genital candidiasis, genital infection, genital infection male, penile infection, vulvitis, vaginitis bacterial, vulval abscess. d Urinary tract infection includes the following preferred terms, listed in order of frequency reported: urinary tract infection, cystitis, Escherichia urinary tract infection, genitourinary tract infection, pyelonephritis, trigonitis, urethritis, kidney infection and prostatitis.

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Nebenwirkungen · Xigduo

Xigduo 5 mg/850 mg film-coated tablets Xigduo 5 mg/1,000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11–12

HOS-128354 · Präparat HOS-096549

11 e Volume depletion includes, e.g. the predefined preferred terms: dehydration, hypovolaemia, hypotension. f Polyuria includes the preferred terms: pollakiuria, polyuria, urine output increased. g Mean changes from baseline in haematocrit were 2.30% for dapagliflozin 10 mg versus -0.33% for placebo. Haematocrit values > 55% were reported in 1.3% of the subjects treated with dapagliflozin 10 mg versus 0.4% of placebo subjects. h Gastrointestinal symptoms such as nausea, vomiting, diarrhoea, abdominal pain and loss of appetite occur most frequently during initiation of therapy and resolve spontaneously in most cases. i Mean percent change from baseline for dapagliflozin 10 mg versus placebo, respectively, was: total cholesterol 2.5% versus 0.0%; HDL cholesterol 6.0% versus 2.7%; LDL cholesterol 2.9% versus -1.0%; triglycerides -2.7% versus -0.7%. j See section 4.4. k Reported in the cardiovascular outcomes study in patients with type 2 diabetes (DECLARE). Frequency is based on annual rate. l Adverse reaction was identified through post-marketing surveillance with the use of dapagliflozin. Rash includes the following preferred terms, listed in order of frequency in clinical trials: rash, rash generalised, rash pruritic, rash macular, rash maculo-papular, rash pustular, rash vesicular, and rash erythematous. In active- and placebo-controlled clinical trials (dapagliflozin, N=5936, All control, N=3403), the frequency of rash was similar for dapagliflozin (1.4%) and all control (1.4%), respectively. * Reported in ≥ 2% of subjects and ≥ 1% more and at least 3 more subjects treated with dapagliflozin 10 mg compared to placebo. ** Reported by the investigator as possibly related, probably related or related to study treatment and reported in ≥ 0.2% of subjects and ≥ 0.1% more and at least 3 more subjects treated with dapagliflozin 10 mg compared to placebo. § Adverse reaction and frequency categories for metformin are based on information from the metformin Summary of Product Characteristics available in the European Union.

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Nebenwirkungen · Xigduo

Xigduo 5 mg/850 mg film-coated tablets Xigduo 5 mg/1,000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 12

HOS-128355 · Präparat HOS-096549

Description of selected adverse reactions Dapagliflozin plus metformin Hypoglycaemia In studies with dapagliflozin in add-on combination with metformin, minor episodes of hypoglycaemia were reported at similar frequencies in the group treated with dapagliflozin 10 mg plus metformin (6.9%) and in the placebo plus metformin group (5.5%). No major events of hypoglycaemia were reported. Similar observations were made for the combination of dapagliflozin with metformin in drug-naive patients.

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Nebenwirkungen · Xigduo

Xigduo 5 mg/850 mg film-coated tablets Xigduo 5 mg/1,000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 12

HOS-128356 · Präparat HOS-096549

In an add-on to metformin and a sulphonylurea study, up to 24 weeks, minor episodes of hypoglycaemia were reported in 12.8% of subjects who received dapagliflozin 10 mg plus metformin and a sulphonylurea and in 3.7% of subjects who received placebo plus metformin and a sulphonylurea. No major events of hypoglycaemia were reported.

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Nebenwirkungen · Xigduo

Xigduo 5 mg/850 mg film-coated tablets Xigduo 5 mg/1,000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 12

HOS-128357 · Präparat HOS-096549

Dapagliflozin Vulvovaginitis, balanitis and related genital infections In the 13-study safety pool, vulvovaginitis, balanitis and related genital infections were reported in 5.5% and 0.6% of subjects who received dapagliflozin 10 mg and placebo, respectively. Most infections were mild to moderate, and subjects responded to an initial course of standard treatment and rarely resulted in discontinuation from dapagliflozin treatment. These infections were more frequent in females (8.4% and 1.2% for dapagliflozin and placebo, respectively), and subjects with a prior history were more likely to have a recurrent infection.

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Nebenwirkungen · Xigduo

Xigduo 5 mg/850 mg film-coated tablets Xigduo 5 mg/1,000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 12

HOS-128358 · Präparat HOS-096549

In the DECLARE study, the number of patients with serious adverse events of genital infections were few and balanced: 2 patients in each of the dapagliflozin and placebo groups.

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Nebenwirkungen · Xigduo

Xigduo 5 mg/850 mg film-coated tablets Xigduo 5 mg/1,000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 12

HOS-128359 · Präparat HOS-096549

Cases of phimosis/acquired phimosis have been reported with dapagliflozin concurrent with genital infections and in some cases, circumcision was required.

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Nebenwirkungen · Xigduo

Xigduo 5 mg/850 mg film-coated tablets Xigduo 5 mg/1,000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 12

HOS-128360 · Präparat HOS-096549

Necrotising fasciitis of the perineum (Fournier’s gangrene) Cases of Fournier’s gangrene have been reported postmarketing in patients taking SGLT2 inhibitors, including dapagliflozin (see section 4.4).

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Nebenwirkungen · Xigduo

Xigduo 5 mg/850 mg film-coated tablets Xigduo 5 mg/1,000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 12–13

HOS-128361 · Präparat HOS-096549

12 In the DECLARE study with 17,160 type 2 diabetes mellitus patients and a median exposure time of 48 months, a total of 6 cases of Fournier’s gangrene were reported, one in the dapagliflozin-treated group and 5 in the placebo group.

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Nebenwirkungen · Xigduo

Xigduo 5 mg/850 mg film-coated tablets Xigduo 5 mg/1,000 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-128362 · Präparat HOS-096549

Hypoglycaemia The frequency of hypoglycaemia depended on the type of background therapy used in each study.

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