Leitlinien & Arzneimittelsicherheit

HOS-097815 · has-adverse-reaction-information · PDF-Seite 7

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 %). 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. 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). 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) 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 dyspn

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HOS-097811 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 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. Current or prior treatment for prostate cancer. Patients who have been diagnosed with cholestasis. Current exacerbation of rectal inflammatory bowel disease (see section 4.4). Any medical condition that precludes the administration of a general anaesthetic or invasive procedures. 3

HOS-097810 · has-indication-information · PDF-Seite 2

TOOKAD is indicated as monotherapy for adult patients with previously untreated, unilateral, low-risk, adenocarcinoma of the prostate with a life expectancy ≥ 10 years and: - Clinical stage T1c or T2a, - Gleason Score ≤ 6, based on high-resolution biopsy strategies, - PSA ≤ 10 ng/mL, - 3 positive cancer cores with a maximum cancer core length of 5 mm in any one core or 1-2 positive cancer cores with ≥ 50 % cancer involvement in any one core or a PSA density ≥ 0.15 ng/mL/cm3.

HOS-097813 · has-interaction-information · PDF-Seite 6

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). 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. 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 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). 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.

HOS-097814 · has-pregnancy-information · PDF-Seite 7

Contraception If the patient is sexually active with women who are capable of getting pregnant, he and/or his partner should use an effective form of birth control to prevent getting pregnant during a period of 90 days after the VTP procedure. Pregnancy and breast-feeding TOOKAD is not indicated for the treatment of women. Fertility Padeliporfin has not been tested for reproductive toxicity and fertility. However, all stages of spermatogenesis have been observed in animal. Minimal seminiferous epithelial degeneration was also recorded in one high-dose male with vacuolation. All these changes were considered to be incidental and probably related to the intravenous administration procedure.

HOS-097812 · has-warning-information · PDF-Seite 4

Tumour localisation Before treatment, the tumour must be accurately located and confirmed as unilateral using high-resolution biopsy strategies based on current best practice, such as multi-parametric MRI-based strategies or template-based biopsy procedures. Simultaneous treatment of both prostate lobes was associated with an inferior outcome in clinical studies and should not be performed. Insufficient patients underwent retreatment of the ipsilateral lobe or sequential treatment of the contralateral lobe to determine the efficacy and safety of a second TOOKAD-VTP procedure. Follow-up post TOOKAD-VTP There is limited biopsy data beyond 2 years after TOOKAD treatment, so long-term efficacy has not been determined. Residual tumour has been found on follow-up biopsy of the treated lobe at 12 and 24 months, usually outside of the treated volume, but occasionally within the area of necrosis. There is limited data on long-term outcomes and on potential consequences of post-TOOKAD local scarring in case of disease progression. At present TOOKAD-VTP has been shown to defer the need for radical therapy and its associated toxicity. Longer follow-up will be required to determine whether TOOKAD-VTP will be curative in a proportion of patients. Following TOOKAD VTP, patients should undergo digital rectal examination (DRE) and have their serum PSA monitored, including an assessment of PSA dynamics (PSA doubling time and PSA velocity). PSA should be tested every 3 months for first 2 years post VTP and every 6-months thereafter in order to assess PSA dynamics (PSA Doubling Time (DT), PSA velocity). Digital Rectal Examination (DRE) is recommended to be performed at least once a year and more often if clinically justified.Routine biopsy is recommended at 2-4 years and 7 years post VTP, with additional biopsies based on clinical/ PSA assessment. mpMRI may be used to improve the decision making but not, at present, to replace biopsy. In case of positive biopsies, patients who exceed the threshold for low risk disease (i.e. have GS > 6, > 3 positive cores or any single core length > 5mm) should receive a treatment recommendation for radical therapy. Radical therapy post VTP procedure The safety and efficacy of subsequent radical therapy (surgery or radiotherapy) is uncertain. Limited information is available regarding the safety and efficacy of radical prostatectomy after TOOKAD-VTP. In small surgical series, there have been reports of T3 tumours, positive margins and i

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