Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Tookad

TOOKAD 183 mg powder for solution for injection TOOKAD 366 mg powder for solution for injection · Abschnitt 4.3 · PDF-Seite 3

HOS-136003 · Präparat HOS-097808

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

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

Gegenanzeigen · Tookad

TOOKAD 183 mg powder for solution for injection TOOKAD 366 mg powder for solution for injection · Abschnitt 4.3 · PDF-Seite 3

HOS-136004 · Präparat HOS-097808

Any previous prostatic interventions where the internal urinary sphincter may have been damaged, including trans-urethral resection of the prostate (TURP) for benign prostatic hypertrophy.

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

Gegenanzeigen · Tookad

TOOKAD 183 mg powder for solution for injection TOOKAD 366 mg powder for solution for injection · Abschnitt 4.3 · PDF-Seite 3

HOS-136005 · Präparat HOS-097808

Current or prior treatment for prostate cancer.

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

Gegenanzeigen · Tookad

TOOKAD 183 mg powder for solution for injection TOOKAD 366 mg powder for solution for injection · Abschnitt 4.3 · PDF-Seite 3

HOS-136006 · Präparat HOS-097808

Patients who have been diagnosed with cholestasis.

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

Gegenanzeigen · Tookad

TOOKAD 183 mg powder for solution for injection TOOKAD 366 mg powder for solution for injection · Abschnitt 4.3 · PDF-Seite 3

HOS-136007 · Präparat HOS-097808

Current exacerbation of rectal inflammatory bowel disease (see section 4.4).

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

Gegenanzeigen · Tookad

TOOKAD 183 mg powder for solution for injection TOOKAD 366 mg powder for solution for injection · Abschnitt 4.3 · PDF-Seite 3

HOS-136008 · Präparat HOS-097808

Any medical condition that precludes the administration of a general anaesthetic or invasive procedures.

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

Wechselwirkungen · Tookad

TOOKAD 183 mg powder for solution for injection TOOKAD 366 mg powder for solution for injection · Abschnitt 4.5 · PDF-Seite 6

HOS-136009 · Präparat HOS-097808

OATP1B1 and OATP1B3 transporters In vitro studies predict that TOOKAD at therapeutic concentrations is unlikely to inhibit cytochrome P450 enzymes but could inhibit OATP1B1 and OATP1B3 transporters (see section 5.2).

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

Wechselwirkungen · Tookad

TOOKAD 183 mg powder for solution for injection TOOKAD 366 mg powder for solution for injection · Abschnitt 4.5 · PDF-Seite 6

HOS-136010 · Präparat HOS-097808

The magnitude of interaction has not been investigated clinically but a transient increase in the plasma concentration of co-administered substrates of OATP1B1 and OATP1B3 cannot be ruled out. The use of medicinal products that are substrates of OATP1B1 or OATP1B3 (repaglinide, atorvastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin, bosentan, glyburide) for which concentration-dependent serious adverse reactions have been observed should be avoided on the day of TOOKAD infusion and for at least 24 hours after administration. Co-administration should be done with caution and close monitoring is recommended.

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): atorvastatin (HOS-086304) simvastatin (HOS-086158) rosuvastatin (HOS-086307) glyburide (HOS-109273) bosentan (HOS-086291) repaglinide (HOS-086935) pravastatin (HOS-086306) pitavastatin (HOS-125743)

Wechselwirkungen · Tookad

TOOKAD 183 mg powder for solution for injection TOOKAD 366 mg powder for solution for injection · Abschnitt 4.5 · PDF-Seite 6

HOS-136012 · Präparat HOS-097808

Photosensitisers Medicinal products which have potential photosensitising effects (such as tetracyclines, sulphonamides, quinolones, phenothiazines, sulfonylurea hypoglycaemic agents, thiazide diuretics, griseofulvin or amiodarone) should be stopped at least 10 days before the procedure with TOOKAD and for at least 3 days after the procedure or replaced by other treatments without photosensitising properties. If it is not possible to stop a photosensitising medicinal product (such as amiodarone), the

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): griseofulvin (HOS-091156) amiodarone (HOS-085596)

Wechselwirkungen · Tookad

TOOKAD 183 mg powder for solution for injection TOOKAD 366 mg powder for solution for injection · Abschnitt 4.5 · PDF-Seite 6–7

HOS-136014 · Präparat HOS-097808

6 patient should be advised that increased sensitivity to sunlight may occur and they may need to protect themselves from direct light exposure for a longer period (see section 4.2).

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

Wechselwirkungen · Tookad

TOOKAD 183 mg powder for solution for injection TOOKAD 366 mg powder for solution for injection · Abschnitt 4.5 · PDF-Seite 7

HOS-136015 · Präparat HOS-097808

Anticoagulants and antiplatelet agents Anticoagulant medicinal products and those that decrease platelet aggregation (e.g. acetylsalicylic acid) should be stopped at least 10 days before the procedure with TOOKAD. Medicinal products that prevent or reduce platelet aggregation should not be started for at least 3 days after the procedure.

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

Nebenwirkungen · Tookad

TOOKAD 183 mg powder for solution for injection TOOKAD 366 mg powder for solution for injection · Abschnitt 4.8 · PDF-Seite 7

HOS-136016 · Präparat HOS-097808

Summary of the safety profile The most frequently reported adverse reactions in the Phase II and III clinical studies were urinary and reproductive system disorders: dysuria (25.1 %), erectile dysfunction (21.1 %), haematuria (19.6 %), perineal pain/haematoma (15.3 %), urinary retention (13.3 %), micturition urgency (9.0 %), pollakiuria (7.3 %), urinary tract infection (5.5 %), incontinence (5.3 %) and ejaculation failure (5.0 %).

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

Nebenwirkungen · Tookad

TOOKAD 183 mg powder for solution for injection TOOKAD 366 mg powder for solution for injection · Abschnitt 4.8 · PDF-Seite 7

HOS-136017 · Präparat HOS-097808

Unspecific adverse events probably linked to the general anaesthesia were also observed: transient global amnesia, bradycardia, sinus arrhythmia, atrial fibrillation, hypotension, bronchospasm, pharyngeal inflammation, respiratory tract congestion, nausea, vomiting, constipation, pyrexia, procedural hypotension. Some cases of hepatotoxicity (1.5 %), such as elevation of transaminases, were also reported. All of them were mild in intensity.

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

Nebenwirkungen · Tookad

TOOKAD 183 mg powder for solution for injection TOOKAD 366 mg powder for solution for injection · Abschnitt 4.8 · PDF-Seite 7

HOS-136018 · Präparat HOS-097808

Tabulated list of adverse reactions Adverse reactions reported are listed below in Table 1 by organ class and frequency. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100).

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

Nebenwirkungen · Tookad

TOOKAD 183 mg powder for solution for injection TOOKAD 366 mg powder for solution for injection · Abschnitt 4.8 · PDF-Seite 7–8

HOS-136019 · Präparat HOS-097808

7 Table 1: Summary of adverse reactions considered related to TOOKAD and/or the study device and/or the study procedure in the pooled safety analysis (N=398)

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

Nebenwirkungen · Tookad

TOOKAD 183 mg powder for solution for injection TOOKAD 366 mg powder for solution for injection · Abschnitt 4.8 · PDF-Seite 8

HOS-136020 · Präparat HOS-097808

System organ class Frequency Adverse reaction Infections and infestations Common Genito-urinary tract infection1 Uncommon Prostatic abscess Psychiatric disorders Uncommon Libido decreased Affective disorder Encopresis Nervous system disorders Uncommon Headache Dizziness Sciatica Sensory disturbance Formication Eye disorders Uncommon Eye irritation Photophobia Vascular disorders Common Haematoma Hypertension Respiratory, thoracic and Uncommon Exertional dyspnoea mediastinal disorders Gastrointestinal disorders Common Haemorrhoids Anorectal discomfort2 Abdominal pain Rectal haemorrhage3 Uncommon Abdominal discomfort Abnormal faeces Diarrhoea Hepatobiliary disorders Common Hepatotoxicity4 Skin and subcutaneous tissue Common Ecchymosis disorders Uncommon Rash Erythema Dry skin Pruritus Skin depigmentation Skin reaction Muscular and connective tissue Common Back pain5 disorders Uncommon Groin pain Muscle haemorrhage Haemarthrosis Musculoskeletal pain Pain in extremity Renal and urinary disorders Very common Urinary retention Haematuria Dysuria6 Micturition disorders7 Common Urethral stenosis Urinary incontinence8 Uncommon Ureteric haemorrhage Urethral haemorrhage Urinary tract disorders

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

Nebenwirkungen · Tookad

TOOKAD 183 mg powder for solution for injection TOOKAD 366 mg powder for solution for injection · Abschnitt 4.8 · PDF-Seite 8–9

HOS-136021 · Präparat HOS-097808

8  System organ class Frequency Adverse reaction Reproductive system and Very common Perineal pain9 breast disorders Male sexual dysfunction10 Common Prostatitis Genital pain11 Prostatic pain12 Haematospermia Uncommon Genital haemorrhage Penile swelling13 Prostatic haemorrhage Testicular swelling General disorders and Common Fatigue administration site conditions Uncommon Asthenia Catheter site pain Laser device failure Infusion site bruising Nodule Pain Application site erythema Investigations Common Abnormal clotting14 Uncommon Blood lactate dehydrogenase increased Blood triglyceride increased Gamma-glutamyltransferase increased Blood cholesterol increased Blood creatine phosphokinase increased Blood potassium decreased Low density lipoprotein increased Neutrophil count increased PSA increased Weight decreased White blood cell count increased Injury, poisoning and Common Perineal injury15 procedural complications Uncommon Surgical procedure repeated Contusion Post-procedural urine leak Procedural pain Post-procedural discharge Fall

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

Nebenwirkungen · Tookad

TOOKAD 183 mg powder for solution for injection TOOKAD 366 mg powder for solution for injection · Abschnitt 4.8 · PDF-Seite 9–10

HOS-136022 · Präparat HOS-097808

The following terms represent a group of adverse reactions that describes a medical condition rather than a single event. 1 Genito-urinary tract infection (urinary tract infection, orchitis, epididymitis, cystitis). 2 Anorectal discomfort (proctalgia, rectal tenesmus). 3 Rectal haemorrhage (anal haemorrhage). 4 Hepatotoxicity (alanine aminotransferase increased, aspartate aminotransferase increased). 5 Back pain (intervertebral disc protrusion). 6 Dysuria (bladder pain, bladder spasm, hypertonic bladder, urethral spasm, urinary tract pain). 7 Micturition disorders (micturition urgency, pollakiuria, nocturia, urine flow decreased, urinary straining). 8 Urinary incontinence (urge incontinence, incontinence, stress urinary incontinence). 9 Perineal pain (pelvic pain). 10 Male sexual dysfunction (erectile dysfunction, ejaculation failure, dyspareunia, ejaculation disorder, hypospermia, painful ejaculation, retrograde ejaculation, sexual dysfunction, semen volume decreased). 11 Genital pain (penile pain, testicular pain, scrotal pain, non-infective orchitis, spermatic cord inflammation, genital contusion). 9 12 Prostatic pain (prostatism, prostatic disorders, prostatic fibrosis). 13 Penile swelling (balanoposthitis). 14 Abnormal clotting (fibrin D dimer increased, aPTT prolonged, INR increased). 15 Perineal injury (post-procedural haematoma, necrosis, perineal haematoma, pelvic haematoma).

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

Nebenwirkungen · Tookad

TOOKAD 183 mg powder for solution for injection TOOKAD 366 mg powder for solution for injection · Abschnitt 4.8 · PDF-Seite 10

HOS-136023 · Präparat HOS-097808

Description of selected adverse reactions

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

Nebenwirkungen · Tookad

TOOKAD 183 mg powder for solution for injection TOOKAD 366 mg powder for solution for injection · Abschnitt 4.8 · PDF-Seite 10

HOS-136024 · Präparat HOS-097808

Erectile dysfunction In the Phase III European study, 60 (30.5 %) of patients in the TOOKAD-VTP arm experienced erectile dysfunction and 16 (8.1 %) experienced ejaculation failure. 53 (26.9 %) patients experienced erectile dysfunction for more than 6 months, including 34 (17.3 %) patients in whom the erectile dysfunction had not resolved at the end of the study. When the analysis was restricted to patients that underwent unilateral VTP, 33 (16.8 %) patients experienced erectile dysfunction for more than 6 months, including 17 (8.6 %) patients in whom the erectile dysfunction had not resolved at the end of the study.

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