Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Talmanco (previously Tadalafil Generics)

Talmanco 20 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-137548 · Präparat HOS-098059

CYP1A2 substrates (e.g. theophylline) When tadalafil 10 mg was administered with theophylline (a non-selective phosphodiesterase inhibitor) there was no pharmacokinetic interaction. The only pharmacodynamic effect was a small (3.5 beats per minutes [bpm]) increase in heart rate.

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): theophylline (HOS-085910)

Wechselwirkungen · Talmanco (previously Tadalafil Generics)

Talmanco 20 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-137549 · Präparat HOS-098059

CYP2C9 substrates (e.g.R-warfarin) Tadalafil (10 mg and 20 mg) had no clinically significant effect on exposure (AUC) to S-warfarin or R-warfarin (CYP2C9 substrate), nor did tadalafil affect changes in prothrombin time induced by warfarin.

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): prothrombin (HOS-085093) warfarin (HOS-085950)

Wechselwirkungen · Talmanco (previously Tadalafil Generics)

Talmanco 20 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-137550 · Präparat HOS-098059

Acetylsalicylic acid Tadalafil (10 mg and 20 mg) did not potentiate the increase in bleeding time caused by acetyl salicylic acid.

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

Wechselwirkungen · Talmanco (previously Tadalafil Generics)

Talmanco 20 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-137551 · Präparat HOS-098059

P-glycoprotein substrates (e.g. digoxin) Tadalafil (40 mg once per day) had no clinically significant effect on the pharmacokinetics of digoxin.

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)

Wechselwirkungen · Talmanco (previously Tadalafil Generics)

Talmanco 20 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-137552 · Präparat HOS-098059

Oral contraceptive At steady-state, tadalafil (40 mg once per day) increased ethinylestradiol exposure (AUC) by 26 % and Cmax by 70 % relative to oral contraceptive administered with placebo. There was no statistically significant effect of tadalafil on levonorgestrel which suggests the effect of ethinylestradiol is due to inhibition of intestinal sulphation by tadalafil. The clinical relevance of this finding is uncertain.

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): placebo (HOS-088378) levonorgestrel (HOS-089677)

Wechselwirkungen · Talmanco (previously Tadalafil Generics)

Talmanco 20 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-137553 · Präparat HOS-098059

Terbutaline A similar increase in AUC and Cmax seen with ethinylestradiol may be expected with oral administration of terbutaline, probably due to inhibition of intestinal sulphation by tadalafil. The clinical relevance of this finding is uncertain.

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): terbutaline (HOS-085475)

Wechselwirkungen · Talmanco (previously Tadalafil Generics)

Talmanco 20 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7–8

HOS-137554 · Präparat HOS-098059

7 Alcohol Alcohol concentrations were not affected by co-administration with tadalafil (10 mg or 20 mg). In addition, no changes in tadalafil concentrations were seen after co-administration with alcohol. Tadalafil (20 mg) did not augment the mean blood pressure decrease produced by alcohol (0.7 g/kg or approximately 180 mL of 40 % alcohol [vodka] in an 80 kg male), but in some subjects, postural dizziness and orthostatic hypotension were observed. The effect of alcohol on cognitive function was not augmented by tadalafil (10 mg).

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

Wechselwirkungen · Talmanco (previously Tadalafil Generics)

Talmanco 20 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-137555 · Präparat HOS-098059

Paediatric population

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

Wechselwirkungen · Talmanco (previously Tadalafil Generics)

Talmanco 20 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-137556 · Präparat HOS-098059

Interaction studies have only been performed in adults.

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

Wechselwirkungen · Talmanco (previously Tadalafil Generics)

Talmanco 20 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-137557 · Präparat HOS-098059

Based upon population PK analysis, the estimates of apparent clearance (CL/F) and the effect of bosentan on CL/F in paediatric patients are similar to those in adult patients with PAH. No dose adjustment is considered necessary for tadalafil with bosentan use.

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): bosentan (HOS-086291)

Nebenwirkungen · Talmanco (previously Tadalafil Generics)

Talmanco 20 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-137558 · Präparat HOS-098059

Summary of the safety profile The most commonly reported adverse reactions, occurring in ≥ 10 % of patients in the tadalafil 40 mg treatment arm, were headache, nausea, back pain, dyspepsia, flushing, myalgia, nasopharingitis and pain in extremity. The adverse reactions reported were transient, and generally mild or moderate. Adverse reaction data are limited in patients over 75 years of age.

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

Nebenwirkungen · Talmanco (previously Tadalafil Generics)

Talmanco 20 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-137559 · Präparat HOS-098059

In the pivotal placebo-controlled study of tadalafil for the treatment of PAH, a total of 323 patients were treated with tadalafil at doses ranging from 2.5 mg to 40 mg once daily and 82 patients were treated with placebo. The duration of treatment was 16 weeks. The overall frequency of discontinuation due to adverse events was low (tadalafil 11 %, placebo 16 %). Three hundred and fifty seven (357) patients who completed the pivotal study entered a long-term extension study. Doses studied were 20 mg and 40 mg once daily.

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

Nebenwirkungen · Talmanco (previously Tadalafil Generics)

Talmanco 20 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8–9

HOS-137560 · Präparat HOS-098059

8 Tabulated list of adverse reactions The table below lists the adverse reactions reported during the placebo-controlled clinical trial in patients with PAH treated with tadalafil. Also included in the table are some adverse reactions which have been reported in clinical trials and/or post marketing with tadalafil in the treatment of male erectile dysfunction. These events have either been assigned a frequency of “Not known,” as the frequency in PAH patients cannot be estimated from the available data or assigned a frequency based on the clinical trial data from the pivotal placebo-controlled study of tadalafil.

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

Nebenwirkungen · Talmanco (previously Tadalafil Generics)

Talmanco 20 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 9

HOS-137561 · Präparat HOS-098059

Frequency estimate: 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).

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

Nebenwirkungen · Talmanco (previously Tadalafil Generics)

Talmanco 20 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 9

HOS-137562 · Präparat HOS-098059

Very common Common Uncommon Rare Not known1 Immune system disorders Hypersensitivity Angioedema reactions5 Nervous system disorders Headache6 Syncope, Migraine5 Seizures5, Stroke2 (including Transient amnesia5 haemorrhagic events) Eye disorders Blurred vision Non-arteritic anterior ischemic optic neuropathy (NAION), Retinal vascular occlusion, Visual field defect, Central serous chorioretinopathy Ear and labyrinth disorders Tinnitus Sudden hearing loss Cardiac disorders Palpitations2, 5 Sudden cardiac Unstable angina death2, 5, pectoris, Tachycardia2, 5 Ventricular arrhythmia, Myocardial Infarction2 Vascular disorders Flushing Hypotension Hypertension Respiratory, thoracic and mediastinal disorders Nasopharyngitis Epistaxis (including nasal congestion, sinus congestion and rhinitis) Gastrointestinal disorders Nausea, Dyspepsia Vomiting, (including abdominal Gastroesophageal pain/discomfort3) reflux Skin and subcutaneous tissue disorders Rash Urticaria5, Stevens-Johnson Hyperhydrosis Syndrome, (sweating)5 Exfoliative dermatitis Musculoskeletal and connective tissue disorders Myalgia, Back pain, Pain in extremity (including limb discomfort)

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

Nebenwirkungen · Talmanco (previously Tadalafil Generics)

Talmanco 20 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 9–10

HOS-137563 · Präparat HOS-098059

9  Very common Common Uncommon Rare Not known1 Renal and urinary disorders Haematuria Reproductive system and breast disorders Increased uterine Priapism5, Penile Prolonged erections bleeding4 haemorrhage, Haematospermia General disorders and administration site conditions Facial oedema, Chest pain2 1 Events not reported in registration trials and cannot be estimated from the available data. The adverse reactions have been included in the table as a result of postmarketing or clinical trial data from the use of tadalafil in the treatment of erectile dysfunction. 2 Most of the patients in whom these events have been reported had pre-existing cardiovascular risk factors. 3 Actual MedDRA terms included are abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, and stomach discomfort. 4 Clinical non-MedDRA term to include reports of abnormal/excessive menstrual bleeding conditions such as menorrhagia, metrorrhagia, menometrorrhagia, or vaginal haemorrhage. 5 The adverse reactions have been included in the table as a result of post-marketing or clinical trial data from the use of tadalafil in the treatment of erectile dysfunction; and in addition, the frequency estimates are based on only 1 or 2 patients experiencing the adverse reaction in the pivotal placebo-controlled study of tadalafil. 6 Headache was the most commonly reported adverse reaction. Headache may occur at the beginning of therapy; and decreases over time even if treatment is continued.

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

Nebenwirkungen · Talmanco (previously Tadalafil Generics)

Talmanco 20 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10

HOS-137564 · Präparat HOS-098059

Paediatric population

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

Nebenwirkungen · Talmanco (previously Tadalafil Generics)

Talmanco 20 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10

HOS-137565 · Präparat HOS-098059

A total of 51 paediatric patients aged from 2.5 to 17 years with PAH were treated with tadalafil in clinical trials (H6D-MC-LVHV, H6D-MC-LVIG). A total of 391 paediatric patients with PAH, from new-born to < 18 years, were treated with tadalafil in an observational post-marketing study (H6D-JETD01). Following tadalafil administration, the frequency, type and severity of adverse reactions in children and adolescents were similar to that seen for adults. Due to differences in study design, sample size, gender, age range, and doses, safety findings from these trials are detailed separately below.

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

Nebenwirkungen · Talmanco (previously Tadalafil Generics)

Talmanco 20 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10

HOS-137566 · Präparat HOS-098059

Placebo-controlled clinical trial in paediatric patients (H6D-MC-LVHV) In a randomised, placebo-controlled study in 35 patients aged 6.2 to 17.9 years (median age of 14.2 years) with PAH, a total of 17 patients were treated once daily with tadalafil 20 mg (middle-weight cohort, ≥ 25 kg to < 40 kg) or 40 mg (heavy-weight cohort, ≥ 40 kg), and 18 patients were treated with placebo, for 24 weeks. The most common AEs, occurring in ≥ 2 patients treated with tadalafil, were headache (29.4 %), upper respiratory tract infection and influenza (17.6 % each), and arthralgia and epistaxis (11.8 % each). No deaths or SAEs were reported. Of the 35 paediatric patients treated in the short-term, placebo-controlled study, 32 entered the 24 month long-term open-label extension and 26 patients completed the follow-up. No new safety signals were observed.

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

Nebenwirkungen · Talmanco (previously Tadalafil Generics)

Talmanco 20 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10

HOS-137567 · Präparat HOS-098059

Uncontrolled pharmacokinetic study in paediatric patients (H6D-MC-LVIG) In a paediatric multiple ascending dose study, 19 patients with a median age of 10.9 years [range 2.5 – 17 years] received once daily tadalafil, for an open-label treatment duration of 10 weeks (Period 1) and for up to a further 24 months in an extension (Period 2). SAEs were reported in 8 patients (42.1 %). These were pulmonary hypertension (21.0 %), viral infection (10.5 %), and cardiac failure, gastritis, pyrexia, type 1 diabetes mellitus, febrile convulsion, presyncope, seizure, and ovarian cyst (5.3 % each). No patient was discontinued due to AEs. TEAEs were reported in 18 patients (94.7 %) and the most frequent TEAEs (occurring in ≥ 5 patients) were headache, pyrexia, viral upper respiratory tract infection, and vomiting. Two deaths were reported.

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