Tookad

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
TOOKAD 183 mg powder for solution for injection 
TOOKAD 366 mg powder for solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
TOOKAD 183 mg powder for solution for injection 
Each vial contains 183 mg of padeliporfin (as di-potassium salt). 
 
TOOKAD 366 mg powder for solution for injection 
Each vial contains 366 mg of padeliporfin (as di-potassium salt). 
 
1 mL of reconstituted solution contains 9.15 mg of padeliporfin. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder for solution for injection. The powder is a dark lyophilisate. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
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. 
 
4.2 Posology and method of administration 
 
TOOKAD is restricted to hospital use only. It should only be used by personnel trained in the 
Vascular-Targeted Photodynamic therapy (VTP) procedure. 
 
Posology 
The recommended posology of TOOKAD is one single dose of 3.66 mg/kg of padeliporfin. 
 
TOOKAD is administered as part of focal VTP. The VTP procedure is performed under general 
anaesthetic after rectal preparation. Prophylactic antibiotics and alpha-blockers may be prescribed at 
the physician’s discretion.  
Retreatment of the same lobe or sequential treatment of the contralateral lobe of the prostate are not 
recommended (see section 4.4). 
 



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Special populations 
 
Hepatic impairment 
No data are available in patients with hepatic impairment. Exposure to padeliporfin is expected to be 
increased and/or prolonged in patients with hepatic impairment. No specific dosage recommendation 
can be given. TOOKAD should be used with caution in patients with severe hepatic impairment. 
 
TOOKAD is contraindicated in patients who have been diagnosed with cholestasis (see section 4.3). 
 
Renal impairment 
There is minimal renal excretion of TOOKAD so no adjustment in dose is required in patients with 
renal impairment. 
This medicinal product contains potassium. This should be taken into consideration (see section 4.4). 
 
Elderly 
No specific posology adjustment is necessary in this population (see section 5.2). 
 
Paediatric population 
There is no relevant use of TOOKAD in the paediatric population in the treatment of low-risk 
localised prostate cancer. 
 
Method of administration 
TOOKAD is for intravenous use. For instructions on reconstitution of TOOKAD before 
administration, see section 6.6. 
 
Illumination for photoactivation of TOOKAD 
The solution is administered by intravenous injection over 10 minutes. Then the prostate is illuminated 
immediately for 22 minutes 15 seconds by laser light at 753 nm delivered via interstitial optical fibres 
from a laser device at a power of 150 mW/cm of fibre, delivering an energy of 200 J/cm. 
Planning of optical fibre positioning should be performed at the beginning of the procedure using the 
treatment guidance software. During the procedure, the number and the length of the optical fibres are 
selected depending on the shape and the size of the prostate and the optical fibres are positioned 
transperineally into the prostate gland under ultrasound guidance to achieve a Light Density Index 
(LDI) ≥ 1 in the targeted tissue. Treatment should not be undertaken in patients where an LDI ≥ 1 
cannot be achieved (see section 5.1). 
 
4.3 Contraindications 
 
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. 
 
 



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4.4 Special warnings and precautions for use 
 
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 trials 
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 
impotence. In the 24 months of the pivotal European Phase III study, no patients underwent radical 
radiotherapy post TOOKAD-VTP.  
 
Photosensitivity 
There is a risk of skin and eye photosensitivity with exposure to light post TOOKAD-VTP.  
 
It is important that all patients follow the light precautions below for 48 hours post-procedure to 
minimize the risk of damage to the skin and eyes.  
 
Patients should avoid exposure to direct sunlight (including through windows) and all bright light 
sources, both indoors and outdoors. This includes sunbeds, bright computer monitor screens and 
medical examination lights, such as ophthalmoscopes, otoscopes and endoscopy equipment, for 
48 hours following the VTP procedure. 
 
Sunscreen creams do not protect against near infra-red light and, therefore, do not provide adequate 
protection. 
 



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If the patient reports discomfort to the skin or eyes during hospitalisation, reduce the level of lighting 
and take extra care to shield the patient from artificial and natural light. 
 
First 12 hours after VTP procedure 
The patient should wear protective goggles and be kept under medical surveillance for at least 6 hours 
in a room with dimmed light. 
 
The patient may be discharged in the evening of the same day at the physician’s discretion. 
 
The patient must stay in a dimmed light environment without any direct exposure of the skin and the 
eyes to daylight. The patient may only use incandescent light bulbs with a maximum power of 
60 watts or equivalent (i.e. 6 watts for LED lights, 12 watts for fluorescent low-energy lights). 
 
The patient may watch television from a distance of 2 metres and, from 6 hours onwards, may use 
electronic devices such as smartphones, tablets and computers. If the patient must go outdoors during 
daylight hours, he should wear protective clothes and high protection goggles to shield his skin and 
eyes. 
 
12-48 hours after VTP procedure 
The patient may go outdoors during daylight hours but only in shaded areas or when it is overcast. He 
should wear dark clothes and take care when exposing hands and face to the sun. 
 
The patient can return to normal activity and tolerate direct sunlight 48 hours after the procedure. 
 
No patients with photosensitive dermatitis, skin conditions such as porphyria or a history of sensitivity 
to sunlight have received TOOKAD in clinical studies. However, the short duration of action of 
TOOKAD means that the risk of enhanced phototoxicity is expected to be low provided these patients 
strictly follow the precautions against light exposure. 
 
There could be an additional risk of eye photosensitivity in patients who have received intra-occular 
anti-VEGF therapy. Patients who have received prior VEGF therapy should take particular care to 
protect the eyes from light for 48 hours post TOOKAD injection. Concomitant use of systemic VEGF 
inhibitors is not recommended with TOOKAD. 
 
See section 4.5 for interactions with photosensitizing medicinal products. 
 
Erectile dysfunction 
Erectile dysfunction may occur even if radical prostatectomy is avoided. 
Some degree of erectile dysfunction is possible soon after the procedure and may last for more than 
6 months (see section 4.8). 
 
Extraprostatic necrosis 
There may be extraprostatic necrosis in the peri-prostatic fat not associated with clinical symptoms. 
 
Excessive extraprostatic necrosis occurred as a result of incorrect calibration of the laser or placement 
of the light fibres (see section 4.8). In consequence there is a potential risk of damage to adjacent 
structures, such as the bladder and/or rectum, and development of a recto-urethral or external fistula. A 
urinary fistula has occurred in one case due to incorrect fibre placement. 
 
The equipment should be carefully calibrated and use the treatment guidance software to reduce the 
risk of clinically significant extraprostatic necrosis. 
 
Urinary retention/urethral stricture 
Patients with a history of urethral stricture or with urinary flow problems may be at increased risk of 
poor flow and urinary retention post the TOOKAD-VTP procedure. Urinary retention immediately 
post procedure has been attributed to transient prostatic oedema and generally only short term 
recatheterisation was required. 



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Poor urinary flow due to urethral stricture developed some months post procedure. In certain cases, the 
bulbar location suggested that the stenosis was caused by urinary catheterisation. In other cases, 
urethral stenosis may have been a late consequence of TOOKAD-VTP induced necrosis. 
 
Although they were excluded from the clinical trials, there is a potential risk of increased stenosis post 
the TOOKAD-VTP procedure in patients with pre-existing stenosis (see section 4.8). 
 
Urinary incontinence 
The risk of sphincter damage can be minimised by careful planning of the fibre placement using the 
treatment guidance software. Severe long-term urinary incontinence was observed in a patient who 
underwent a previous transurethral prostatectomy (TURP). This event was not considered to be related 
to a faulty procedure but rather the pre-existing damage to the internal urethral sphincter from the 
TURP. The TOOKAD-VTP procedure is contraindicated in patients with any previous prostatic 
interventions where the internal urinary sphincter may have been damaged, including transurethral 
resection of the prostate (TURP) for benign prostatic hypertrophy (see section 4.3). 
 
Inflammatory bowel disease 
TOOKAD-VTP should only be administered after careful clinical evaluation, to patients with a history 
of active rectal inflammatory bowel disease or any condition that may increase the risk of 
recto-urethral fistula formation (see section 4.3). 
 
Use in patients with abnormal clotting 
Patients with abnormal clotting may develop excessive bleeding due to the insertion of the needles 
required to position the light fibres. This may also cause bruising, haematuria and/or local pain. It is 
not expected that a delay in clotting will reduce the effectiveness of the TOOKAD-VTP treatment ; 
however, it is recommended that drugs that affect clotting are stopped prior to and for the immediate 
period following the VTP procedure (see section 4.5). 
 
Use in patients on a controlled potassium diet 
This medicinal product contains potassium and in general the dose (3.66 mg/kg) will be less than 
1 mmol (39 mg) i.e. essentially ‘potassium free’. However, this will be exceeded in patients heavier 
than 115 kg. This should be taken into consideration in patients with reduced kidney function or 
patients on a controlled potassium diet where a rise in serum potassium would be considered 
detrimental (see section 4.2). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
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 events 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 photosensitizing 
properties. If it is not possible to stop a photosensitising medicinal product (such as amiodarone), the 
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). 



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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. 
 
4.6 Fertility, pregnancy and lactation 
 
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. 
 
4.7 Effects on ability to drive and use machines 
 
TOOKAD has no influence on the ability to drive or use machines. However, as the procedure 
includes general anaesthesia, patients should not perform complex tasks like driving or using machines 
until 24 hours after a general anaesthetic is employed. 
 
4.8 Undesirable effects 
 
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). 
 
  



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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 
mediastinal disorders 

Uncommon 
 

Exertional dyspnoea 

Gastrointestinal disorders 
 

Common 
 

Haemorrhoids 
Anorectal discomfort2 
Abdominal pain 
Rectal haemorrhage3 

Uncommon 
 

Abdominal discomfort 
Abnormal faeces 
Diarrhoea 

Hepatobiliary disorders Common Hepatotoxicity4 
Skin and subcutaneous tissue 
disorders 
 

Common Ecchymosis 
Uncommon 
 

Rash 
Erythema 
Dry skin 
Pruritus 
Skin depigmentation 
Skin reaction 

Muscular and connective tissue 
disorders 
 

Common Back pain5 
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 



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System Organ Class Frequency Adverse reaction 
Reproductive system and 
breast disorders 
 

Very common 
 

Perineal pain9 
Male sexual dysfunction10 

Common 
 

Prostatitis 
Genital pain11 
Prostatic pain12 
Haematospermia 

Uncommon 
 

Genital haemorrhage 
Penile swelling13 
Prostatic haemorrhage 
Testicular swelling 

General disorders and 
administration site conditions 
 

Common Fatigue 
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 
procedural complications 

Common Perineal injury15 
Uncommon Surgical procedure repeated 

Contusion 
Post-procedural urine leak 
Procedural pain 
Post-procedural discharge 
Fall 

 
The following terms represent a group of related events 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). 



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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). 
 
Description of selected adverse reactions 
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. 
 
Urinary retention 
In the Phase III European study, 30 (15.2 %) patients experienced urinary retention. The median time 
to onset of urinary retention was 3 days (1-417). The median duration was 10 days (1-344). 
 
Genito-urinary infections 
The most common infections are orchitis, epididymitis and urinary tract infections including cystitis. 
In the Phase III European study, 20 (10.2 %) patients in the TOOKAD-VTP arm experienced 
genito-urinary infection. In 5 (2.5 %) patients, the infection was considered serious. The median time 
to onset of genito-urinary infections was 22.5 days (4-360). The median duration was 21 days (4-197). 
 
Urinary incontinence 
In the Phase III European study, 25 (12.7 %) patients experienced urinary incontinence (including 
incontinence, stress urinary incontinence and urge incontinence). The median time to onset of urinary 
incontinence was 4 days (1-142). In 18 patients the adverse event resolved with a median duration of 
63.5 days (1-360), and the adverse event was still ongoing at the end of the study for 7 patients. Only 
1 (0.5 %) patient had a severe (Grade 3) urinary incontinence. None of these patients required an 
operation for incontinence. 
 
Perineal injury, perineal pain and prostatitis 
Perineal injury and perineal pain occurred in 46 (23.4 %) patients in the controlled Phase III European 
study. In some cases pain relief was required for perineal pain or anorectal discomfort. One patient had 
Grade 3 perineal pain that started 35 weeks after the VTP procedure, and lasted for about 35 weeks 
before resolving without sequelae. 
 
Prostatitis occurred in 7 (3.6 %) patients in the controlled Phase III European study. One patient had 
Grade 3 prostatitis considered as serious that started 4 days after the VTP procedure, and lasted for 
31 days before resolving without sequelae. 
 
Urethral stenosis 
In the pivotal Phase III European study, moderate or severe urethral stenosis developed in 2 (1.0 %) 
patients 5 to 6 months post-procedure. This required urethral dilatation (see section 4.4). 
 
Additional adverse reactions in the Phase II prostate cancer studies and Special Authorization 
Extraprostatic necrosis 
Two cases of excessive extraprostatic necrosis occurred due to incorrect laser calibration without 
clinical sequelae. One case of external urethral fistula occurred due to fibre misplacement (see 
section 4.4). 
 
Phototoxicity 
In a patient treated at 2 mg/kg of TOOKAD, one case of Grade 3 ischaemic optic neuropathy was 
reported 33 days after the VTP procedure. This resolved with a small defect in the visual field. 
 



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Prostatic abscess 
One serious adverse event of prostatic abscess which was considered severe was reported in the study 
performed in Latin America in a patient who had a unilateral VTP procedure. The case resolved within 
three days. 
 
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. 
 
4.9 Overdose 
 
There is limited clinical information on overdose involving TOOKAD. Healthy subjects have been 
exposed to doses up to 15 mg/kg of padeliporfin di-potassium (corresponding to 13.73 mg/kg of 
padeliporfin) without light activation and 23 patients have been treated with 6 mg/kg of padeliporfin 
di-potassium (corresponding to 5.49 mg/kg of padeliporfin) without significant safety issues.  
However, a prolongation of photosensitisation is possible and precautions against light exposure 
should be maintained for an additional 24 hours (see section 4.4). 
 
An overdose of the laser light may increase the risk of undesirable extraprostatic necrosis (see 
section 4.4). 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Sensitizers used in photodynamic/radiation therapy, ATC code: 
L01XD07 
 
Mechanism of action 
Padeliporfin is retained within the vascular system. When activated with 753 nm wavelength laser 
light, padeliporfin triggers a cascade of pathophysiological events resulting in focal necrosis within a 
few days. Activation within the illuminated tumour vasculature, generates oxygen radicals (•OH, O•�2 ) 
causing local hypoxia that induces the release of nitric oxide (•NO) radicals. This results in transient 
arterial vasodilatation that triggers the release of the vasoconstrictor, endothelin-1. Rapid consumption 
of the •NO radicals, by oxygen radicals, leads to the formation of reactive nitrogen species (RNS) (e.g. 
peroxynitrite), in parallel to arterial constriction. In addition, impaired deformability is thought to 
enhance erythrocyte aggregability and formation of blood clots at the interface of the arterial supply 
(feeding arteries) and tumour microcirculation, results in occlusion of the tumour vasculature. This is 
enhanced by RNS-induced endothelial cell apoptosis and initiation of self-propagated tumour cells 
necrosis through peroxidation of their membrane. 
 
Pharmacodynamic effects 
In patients with localised prostate cancer who received TOOKAD-VTP, necrosis was observed by 
Magnetic Resonance Imaging (MRI) at day 7. There was a correlation between the total energy 
delivered and the volume of necrosis observed at day 7. The LDI corresponds to the ratio of the 
cumulative length of illuminated fibre tips (cm) to the volume (cc) of the targeted zone to be treated. 
The targeted zone corresponds to the lobe containing the positive biopsies. Its volume is measured 
after prostate delineation using the treatment guidance software. In Phase II studies, treatment 
conditions corresponding to an LDI ≥ 1 were associated with a mean rate of necrosis of the targeted 
zone at day 7 of 89 % ± 20.75 for unilateral treatment. An LDI ≥ 1 appeared to be associated with a 
greater volume of necrosis on Day 7 MRI and greater share of patients with negative biopsy at 
6 months compared with an LDI < 1 (see section 4.2). 
 

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There was no significant correlation between the percentage of prostate necrosis on Day 7 MRI and 
the likelihood of a negative prostate biopsy at follow-up. 
 
Clinical efficacy and safety 
Phase III Study (PCM301) 
The pivotal open-label Phase III study (PCM301), conducted in 10 European countries, randomised 
413 patients to TOOKAD-VTP arm or AS arm. 
 
The main inclusion criteria were low-risk prostate cancer with Gleason 3 + 3 prostate adenocarcinoma 
as a maximum, two to three cores positive for cancer and a maximum cancer core length of 5 mm in 
any core (at least 3 mm for patients with only one positive core), clinical stage up to T2a, 
PSA ≤ 10 ng/mL, prostate volume equal or greater than 25 cc and less than 70 cc. 
The main exclusion criteria were any prior or current treatment for prostate cancer, any surgical 
intervention for benign prostatic hypertrophy, life expectancy less than 10 years, medical conditions 
which preclude the use of general anaesthesia. 
 
The VTP procedure consisted of a 10 minutes IV injection of 4 mg/kg of TOOKAD followed by 
22 minutes 15 seconds of illumination with 753 nm laser light at 200 J/cm of fibre delivered using 
interstitial optical fibres, inserted transperineally into the prostate gland. In case of unilateral disease, 
focal treatment of one lobe was to be applied. In case of bilateral disease (discovered at entry or during 
follow-up), bilateral treatment was to be applied, either simultaneously or consecutively. Retreatment 
of lobes found positive for cancer at 12-months follow-up was allowed. 
 
AS involved serial absolute PSA measurements and ultrasound-guided prostatic biospy at 12 and 
24 months. 
 
The study had two co-primary endpoints for TOOKAD-VTP in comparison to AS: 
- A: The rate of absence of definite cancer based on histology at 24 months,  
- B: The difference in rate of treatment failure associated with observed progression of disease 
from low to moderate or higher risk prostate cancer. Moderate/higher risk prostate cancer was defined 
as any of the following: > 3 cores definitively positive for cancer; Gleason primary or secondary 
pattern ≥ 4; at least 1 cancer core length > 5 mm; PSA > 10 ng/mL in 3 consecutive measures; T3 
prostate cancer; metastasis; prostate cancer-related death. 
 
All patients had Gleason score ≤ 3 + 3 at baseline.  
 
In each table are also presented the results of patients meeting the indication criteria (patients with 
unilateral low-risk localised prostate cancer excluded the very low-risk) 
 
Table 2 gives baseline characteristics by arm. 
 



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Table 2: PCM301 – Baseline characteristics by arm for the Intention-To-Treat (ITT) population 
and patients meeting the indication criteria 
 
Characteristic 
 ITT population 

Patients meeting indication 
criteria 

TOOKAD- 
VTP arm 
N = 206 

AS arm 
N = 207 

TOOKAD- 
VTP arm 

N = 80 

AS arm 
N = 78 

Age (years) 
Mean (SD) 64.2 (6.70) 62.9 (6.68) 63.9 (6.27) 62.3 (6.32) 
Range: min, max 45, 85 44, 79 48, 74 46, 73 
Patients aged > 75 year 
old, n (%) 

6 (2.9) 6 (2.9) 0 0 

Unilateral disease, n (%) 157 (76.2) 163 (78.7) 80 (100) 78 (100) 
Bilateral disease, n (%) 49 (23.8) 44 (21.3) Not applicable Not applicable 
Clinical stages 

T1, n (%) 178 (86.4) 180 (87.0) 66 (82.5) 71 (91.0) 
T2a, n (%) 28 (13.6) 27 (13.0) 14 (17.5) 7 (9.0) 

Total number of positive cores 
Mean (SD) 2.1 (0.68) 2.0 (0.72) 2.2 (0.74) 2.1 (0.76) 
Range: min, max 1, 3 1, 3 1, 3 1, 3 

Estimated prostate volume (cc) 
Mean (SD) 42.5 (12.49) 42.5 (11.76) 37.2 (9.67) 37.6 (9.63) 
Range: min, max 25, 70 25, 70 25, 68 25, 66 

PSA (ng/mL) 
Mean (SD) 6.19 (2.114) 5.91 (2.049) 6.98 (1.796) 7.12 (1.704) 
Range: min, max 0.1, 10.0 0.5, 10.0 1.0, 10.0 3.1, 10.0 

 
Of the 206 subjects randomised TOOKAD-VTP, 10 did not receive treatment for various reasons 
including study withdrawal, meeting exclusion criteria, non-compliance and other medical events. 
 
Table 3 describes the co-primary efficacy endpoints in the whole prostate gland and in the treated lobe 
(ITT population and patients meeting the indication criteria). 
 
  



14 

Table 3: PCM301 – Co-primary efficacy endpoints – Whole prostate gland and treated lobe(s)* 
– ITT population and patients meeting the indication criteria 
 
Number of subjects with 
 ITT population 

Patients meeting indication 
criteria 

TOOKAD-VTP 
arm 

N = 206 

AS arm 
 

N = 207 

TOOKAD-VTP 
arm 

N = 80 

AS arm 
 

N = 78 
A: Rate of absence of definite cancer based on histology at 24 months 
Negative biopsy, n (%) 101 (49.0)a 28 (13.5)a 36 (45.0)e 8 (10.3)e 
Negative biopsy in the 
treated lobe*, n (%) 

129 (62.6)b 40 (19.3)b 52 (65.0)f 11 (14.1)f 

No biopsy result, n (%) 38 (18.4) 86 (41.5) 11 (13.8) 34 (43.6) 
Subjects who had radical 
therapy leading to 
missing biopsy, n (%) 

12 (5.8) 55 (26.6)c 6 (7.5) 27 (34.6) 

Other reasonsd, n (%) 26 (12.6) 31 (15.0) 5 (6.3) 7 (9.0) 
Positive biopsy, n (%) 67 (32.5) 93 (44.9) 33 (41.3)   36 (46.2) 
Positive biopsy in the 
treated lobe*, n (%) 

39 (18.9) 81 (39.1) 17 (21.3) 33 (42.3) 

aRisk Ratio (95% CI) = 3.62 (2.50 ; 5.26) ; p value < 0.001 
bRisk Ratio (95% CI) = 3.24 (2.41 ; 4.36) ; p value < 0.001 
cAmong the 60 patients who had radical therapy, 5 patients had a Month 24 biopsy 
dFor example: study withdrawal, medical reason, subject refusal 
eRisk Ratio (95% CI) = 4.39 (2.18 ; 8.83) ; p value < 0.001 
fRisk Ratio (95% CI) = 4.61 (2.60 ; 8.16) ; p value < 0.001 

B: Difference in rate of treatment failure associated with observed progression of disease  
Number of subjects 
progressed at Month 24, 
n (%) 

58 (28.2)g 121 (58.5)g 27 (33.8)h   53 (67.9)h  

Progression to Gleason ≥ 4  49 (23.8) 91 (44.0) 19 (23.8)   40 (51.3)  
Number of subjects 
progressed in the treated 
lobe* at Month 24, n (%) 

24 (11.7)i 90 (43.5)i 7 (8.8)j 39 (50.0)j 

gAdjusted Hazard Ratio (95% CI) = 0.34 (0.24 ; 0.46) ; p value ≤ 0.001 
hAdjusted Hazard Ratio (95% CI) = 0.31 (0.20 ; 0.50) ; p value ≤ 0.001 
iAdjusted Hazard Ratio (95% CI) = 0.17 (0.12 ; 0.27) ; p value ≤ 0.001 
jAdjusted Hazard Ratio (95% CI) = 0.11 (0.05 ; 0.25) ; p value ≤ 0.001 
* The treated lobe(s) in the AS arm was defined as the lobe(s) with disease at baseline. 
 
A secondary objective was to determine the difference between the two arms with regard to the rate of 
subsequent radical therapy for prostate cancer. Of 58 patients that progressed in the TOOKAD-VTP 
arm, only 11 underwent radical therapy, 18 patients underwent a second VTP procedure and 29 had 
not received further treatment at the end of the study. Of 121 patients that progressed in the AS arm, 
54 underwent radical therapy and 67 had not received any active treatment at the end of the study. 
Patients in the AS arm were not offered subsequent VTP. In assessing overall tolerability by 
Month 24, post enrolment patients who underwent a radical therapy were also counted in the scoring 
of prostate symptoms and erectile function. 
 
  



15 

Table 4: PCM301 – Number of subjects with radical treatment at 24 months – ITT population 
and patients meeting the indication criteria 
 

Characteristic 
 ITT population 

Patients meeting indication 
criteria 

TOOKAD-VTP 
arm 

N = 206 

AS arm 
N = 207 

TOOKAD-VTP 
arm 

N = 80 

AS arm 
N = 78 

Number of subjects who 
initiated a radical treatment, 
n (%) 

12 (5.8) 62 (29.9) 6 (7.5) 28 (35.9) 

Number of subjects who 
initiated a radical treatment 
after progression, n (%) 

11 (5.3) 54 (26.1) 5 (6.3) 25 (32.1) 

 
Effect on urinary morbidity (IPSS) and erectile function (IIEF) following TOOKAD-VTP 
As shown in Table 5, in PCM301 study, the International Prostate Symptoms Score (IPSS) showed, a 
moderate increase 7 days after the VTP procedure, in both the ITT population and in patients meeting 
the indication criteria. Those results were improved at Month 3 and back to baseline values at 
Month 6, with further improvement until Month 24. In the Active Surveillance arm, the IPSS score 
slightly worsened over time until Month 24. 
 
Table 5: PCM301 – Effect on urinary morbidity (IPSS) – ITT population and patients meeting 
the indication criteria 
 

 
ITT population Patients meeting indication criteria 

 TOOKAD-VTP 
arm AS arm 

TOOKAD-VTP 
arm AS arm 

n Mean score 
(SD) 

n Mean score 
(SD) 

n Mean score 
(SD)  

n Mean score 
(SD) 

Baseline 179 7.6 (6.09) 185 6.6 (5.30) 71 6.7 (5.69) 73 6.0 (4.34) 
Day 7 180 14.8 (8.64) Not applicable 72 14.2 (8.89) Not applicable 
Month 3 179 9.6 (6.86) 190 7.2 (5.75) 71 8.7 (5.72) 72 6.6 (5.11) 
Month 6 182 7.5 (6.06) 189 6.8 (5.84) 74 6.4 (5.33) 73 6.3 (5.36) 
Month 12 177 7.2 (5.85) 173 7.3 (5.95) 71 5.7 (5.01) 68 7.1 (5.75) 
Month 24* 165 6.6 (5.47) 154 8.2 (6.47) 66 5.5 (5.34) 55 8.6 (6.56) 
*Scores at Month 24 include patients who underwent radical therapy 
 
As shown in Table 6, in the VTP arm of PCM301 study, erectile function domain scores of the 
15-question International Index of Erectile Function (IIEF-15) questionnaire showed a marked 
decrease, 7 days after the VTP procedure followed by a subsequent improvement in the following 
months up to Month 24, in the ITT population and in patients meeting the indication criteria.  
 
  



16 

Table 6: PCM301 – Effect on erectile function (IIEF) – ITT population and patients meeting the 
indication criteria 
 

 
ITT population Patients meeting indication criteria 

 TOOKAD-VTP 
arm AS arm 

TOOKAD-VTP 
arm AS arm 

n Mean score 
(SD) 

n Mean score 
(SD) 

n Mean score 
(SD)  

n Mean score 
(SD) 

Baseline 184 18.6 (10.22)  188 20.6 (9.92) 74 18.4 (10.31) 74 20.8 (10.02) 
Day 7 165 11.5 (10.96) Not applicable 68 10.1 (10.82) Not applicable 
Month 3 171 14.7 (10.48) 182 21.0 (9.84) 69 14.3 (10.81) 70 21.7 (9.95) 
Month 6 176 16.1 (9.98) 185 20.4 (9.83)  68 16.9 (9.78) 72 20.6 (9.85) 
Month 12 170 15.1 (10.28)  167 19.9 (10.29) 70 16.7 (10.18) 65 20.4 (10.44) 
Month 24* 159 15.0 (10.70)  152 16.8 (11.17) 62 15.4 (11.11) 54 16.4 (11.10) 
*Scores at Month 24 include patients who underwent radical therapy 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetic properties of TOOKAD were studied in 42 healthy human male subjects 
(without photoactivation) and in 70 patients with localised prostate cancer (after photoactivation). 
 
Distribution 
In healthy human male subjects, the mean volume of distribution ranged from 0.064-0.279 L/kg, for 
posologies from 1.25 to 15 mg/kg of padeliporfin di-potassium indicating distribution into 
extracellular fluid. A similar mean distribution volume was seen in patients with localised prostate 
cancer treated with 2 and 4 mg/kg of padeliporfin di-potassium (0.09-0.10 L/kg respectively).  
Padeliporfin di-potassium is highly bound to human plasma proteins (99 %). 
 
In vitro studies indicate that TOOKAD is unlikely to be a substrate of OATP1B1, OATP1B3, OCT1, 
OATP2B1, P-gp, BCRP, MRP2 or BSEP hepatic uptake transporters. 
 
Biotransformation 
Minimal metabolism of padeliporfin was observed in in vitro metabolism studies in human liver 
microsomes and S9 fractions. No metabolites of padeliporfin were observed in these studies. 
 
No in vitro or in vivo studies have been conducted with radiolabelled padeliporfin. Therefore, the 
possibility for some in vivo metabolism of padeliporfin cannot be fully excluded. 
 
In vitro studies indicate that TOOKAD is unlikely to be an inhibitor of CYP450 enzymes. 
 
In vitro studies indicate that TOOKAD does not inhibit P-gp, OAT1, OAT3, OCT2, OCT1, BCRP and 
BSEP but it could inhibit both OATP1B1 and OATP1B3 transporters (see section 4.5). 
 
Elimination 
Clearance of padeliporfin di-potassium in healthy male subjects treated from 1.25 mg/kg up to 
15 mg/kg of padeliporfin di-potassium ranged from 0.0245 to 0.088 L/h/kg. Based on popPK analysis 
the estimated half-life is 1.19 h ± 0.08 at 4 mg/kg of padeliporfin di-potassium. A similar mean 
clearance range was seen in patients with localised prostate cancer treated with 4 mg/kg and 2 mg/kg 
of padeliporfin di-potassium (0.04-0.06 L/h/kg respectively). Urinary excretion of padeliporfin in 
healthy human subjects was very low (< 0.2 % of the dose). Taking into account its molecular mass 
and the very low urinary excretion of the molecule, faecal elimination is the most probable route of 
elimination in human. 
 



17 

Elderly population 
Very few patients aged over 75 years were enrolled into studies where pharmacokinetic measurements 
were taken so it is not known if there is a difference in these older patients compared to patients less 
than 75 years of age (see sections 4.2 and 5.1). 
 
Linearity/non-linearity 
In healthy human male subjects, the Cmax was shown to be linear from 1.25 mg/kg to 15 mg/kg of 
padeliporfin di-potassium, covering the therapeutic range. 
 
Effects of covariates on pharmacokinetic properties 
The effects of age, weight and race were investigated in healthy volunteers and patients. 
The results of the population PK study showed that age, race, health status and markers of hepatic 
function were unlikely to have a substantial and biologically significant impact on the 
pharmacokinetics of TOOKAD. 
The body weight of patients (range 60-120 kg) presented a minor impact on the TOOKAD 
pharmacokinetic parameters for doses up to 5 mg/kg of padeliporfin di-potassium. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology and repeated dose toxicity. 
 
In vitro genotoxicity testing identified padeliporfin as having weak potential to induce clastogenicity 
when illuminated by ultraviolet (UV); this correlates with the mechanism of action (formation of 
reactive oxygen species). 
 
Padeliporfin was shown to be cytotoxic in the presence of UVA irradiation (in vitro) and considered 
phototoxic in the guinea pig (in vivo). 
 
Carcinogenicity and reproductive toxicity studies have not been conducted with padeliporfin. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Mannitol (E421) 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
Unopened vial 
5 years 
 
After reconstitution 
The chemical and physical stability of TOOKAD after reconstitution with 5 % glucose solution, in its 
vial, has been demonstrated for 8 hours at 15°C-25°C and at 5°C ± 3°C. 
 
From a microbiological point of view, the product should be used immediately. If not used 
immediately, in-use storage times and conditions prior to use are the responsibility of the user. 
 



18 

6.4 Special precautions for storage 
 
Store in a refrigerator (2°C-8°C). 
Keep the vial in the outer carton in order to protect from light. 
 
For storage conditions after reconstitution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
TOOKAD 183 mg powder for solution for injection 
Amber type I glass vial, sealed with a rubber stopper crimped with an aluminium seal and covered 
with a blue plastic flip-off cap, containing 183 mg padeliporfin. 
 
Pack size: 1 vial 
 
TOOKAD 366 mg powder for solution for injection 
Amber type I glass vial, sealed with a rubber stopper crimped with an aluminium seal and covered 
with a white plastic flip-off cap, containing 366 mg padeliporfin. 
 
Pack size: 1 vial 
 
6.6 Special precautions for disposal and other handling 
 
The preparation of the solution should take place in a dimmed-light environment. 
 
TOOKAD is prepared by reconstituting the powder for solution for injection with: 
- 20 mL of 5 % glucose solution for TOOKAD 183 mg, 
- 40 mL of 5 % glucose solution for TOOKAD 366 mg. 
 
The vial should then be swirled gently for 2 minutes. Each mL of the resulting solution will contain 
9.15 mg of padeliporfin. The vial should rest in an upright position for 3 minutes without further 
shaking or moving. Due to the photosensitising properties of TOOKAD, the content of the vial should 
then be transferred into an opaque syringe that should be held in an upright position for 3 minutes to 
ensure any foam disappears. An injection filter of 0.22 µm and an opaque tubing should be used to 
administer the medicinal product to the patient. Standard handling of syringes should follow. 
 
The reconstituted solution is dark. If not used immediately, in-use storage times and conditions prior 
to use are the responsibility of the user. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Steba Biotech S.A. 
7 Place du Théâtre 
L-2613 Luxembourg 
Luxembourg 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/17/1228/001 
EU/1/17/1228/002 
 
 



19 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
10 November 2017 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 
  



20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND 

USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE 

SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 



21 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
LIOF-PHARMA S.L. 
c/ Hermanos Lumiere 5 
Parque Tecnológico Miñano 
01510 Alava 
Spain 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  
 
• Periodic safety update reports  
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
The marketing authorisation holder shall submit the first periodic safety update report for this product 
within 6 months following authorisation. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the marketing authorisation and any agreed subsequent 
updates of the RMP. 
 
An updated RMP should be submitted: 
 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached.  
 

• Additional risk minimisation measures 
 
Prior to launch of TOOKAD in each Member State the marketing authorisation holder (MAH) must 
agree about the content and format of the educational programme, including communication media, 
distribution modalities, and any other aspects of the programme, with the National Competent 
Authority.  
 
The educational programme is aimed at increasing awareness and providing information concerning 
the signs and symptoms of certain important identified risks of padeliporfin, including 
photosensitivity, and also information on the existing therapeutic approaches (including VTP with 
TOOKAD) for the treatment of the type of prostate cancer, potential benefits, risks and uncertainties 
of VTP with TOOKAD. 
 



22 

The MAH shall ensure that in each Member State where TOOKAD is marketed, all healthcare 
professionals and patients/carers who are expected to prescribe and use TOOKAD have access to/are 
provided with the following educational package: 
 
• Patient information guide 
• Physician guideline 
 
The Patient information guide about TOOKAD should contain the following key elements: 
 
• Information on the existing therapeutic approaches (including VTP with TOOKAD) for the 

treatment of the type of prostate cancer 
• Information on the potential benefits, risks and uncertainties of VTP with TOOKAD, including: 

uncertainties on long-lasting benefit of TOOKAD; uncertainties on long-term safety of 
TOOKAD and efficacy/safety of any further treatments required such as radical prostatectomy 

• Information on adverse drug reactions and the likelihood of them getting them, including: 
erectile dysfunction, urinary incontinence, urinary retention/urethral stricture, and 
photosensitivity and the need to follow the rules to protect themselves against the light after the 
procedure for 48 hours. 

 
The Physician guideline about TOOKAD should contain the following key elements: 
 
• The approaches (including VTP with TOOKAD) for the treatment of his prostate cancer and the 

potential benefits, risks and uncertainties of VTP with TOOKAD: 
o To state that information beyond two years after the TOOKAD -VTP procedure is 

limited and consequently, data on the long-term efficacy and safety of TOOKAD-
VTP are currently not available 

o Information on the efficacy/safety of any subsequent treatments required, such as 
radical prostatectomy, is currently lacking 

• Explain what the VTP procedure involves, including the need to follow the rules to protect the 
Patient against light after the procedure for 48 hours, due to the photosensitising effect of 
TOOKAD and provide a copy of the TOOKAD Package Leaflet to the Patient ahead of the VTP 
procedure 

• Explain what side effects the Patient might expect and the likelihood of him getting them 
• Explain the procedure as well as relevant efficacy and safety results of TOOKAD with simple 

graphics included in the Patient Information Guide. 
 
• Obligation to conduct post-authorisation measures 
 
The MAH shall complete, within the stated timeframe, the below measures: 
 
Description Due date 

Post-authorisation efficacy study (PAES): In order to further investigate long-term 
efficacy of TOOKAD and its impact on disease progression including potential impact 
on the efficacy of subsequent radical therapy in patients with low risk prostate cancer 
as well as further characterise the long term safety of TOOKAD, the MAH should 
submit the results of a randomised phase 3 study in patients with localised prostate 
cancer compared to active surveillance (7-year follow-up study including in an depth 
biopsy study) (PCM301 FU5).   

Submission 
of final 
study 
results: 
31/12/2020 

Post-authorisation efficacy study (PAES): In order to further investigate long-term 
efficacy of TOOKAD and its impact on disease progression including potential impact 
on the efficacy of subsequent radical therapy in patients with low risk prostate cancer 
(excluding very low risk) as well as further characterise the long term safety of 
TOOKAD, the MAH should conduct and submit the results of a long-term 
observational cohort study of patients with unilateral low risk localised prostate cancer 
treated with TOOKAD VTP (CLIN1501 PCM401). 

Submission 
of final 
study 
results: 
31/12/2025 

 



23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



24 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



25 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
TOOKAD 183 mg powder for solution for injection 
padeliporfin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains 183 mg of padeliporfin (as di-potassium salt). 
1 mL of reconstituted solution contains 9.15 mg of padeliporfin. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipient: Mannitol 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for solution for injection 
1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Intravenous use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP: 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Keep the vial in the outer carton in order to protect from light. 
 
 



26 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Steba Biotech S.A. 
7 Place du Théâtre 
L-2613 Luxembourg 
Luxembourg 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/17/1228/001 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
  



27 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
TOOKAD 183 mg powder for solution for injection 
padeliporfin  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains 183 mg of padeliporfin (as di-potassium salt). 
1 mL of reconstituted solution contains 9.15 mg of padeliporfin. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipient: Mannitol 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for solution for injection 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Intravenous use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP: 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Keep the vial in the outer carton in order to protect from light. 
 
 



28 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Steba Biotech S.A. 
7 Place du Théâtre 
L-2613 Luxembourg 
Luxembourg 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/17/1228/001 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Not applicable. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Not applicable. 
 
  



29 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
TOOKAD 366 mg powder for solution for injection 
padeliporfin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains 366 mg of padeliporfin (as di-potassium salt). 
1 mL of reconstituted solution contains 9.15 mg of padeliporfin. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipient: Mannitol 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for solution for injection 
1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Intravenous use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP: 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Keep the vial in the outer carton in order to protect from light. 
 
 



30 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Steba Biotech S.A. 
7 Place du Théâtre 
L-2613 Luxembourg 
Luxembourg 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1228/002 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
  



31 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
TOOKAD 366 mg powder for solution for injection 
padeliporfin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains 366 mg of padeliporfin (as di-potassium salt). 
1 mL of reconstituted solution contains 9.15 mg of padeliporfin. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipient: Mannitol 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for solution for injection 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Intravenous use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP: 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Keep the vial in the outer carton in order to protect from light. 
 
 



32 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Steba Biotech S.A. 
7 Place du Théâtre 
L-2613 Luxembourg 
Luxembourg 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/17/1228/002 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Not applicable. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Not applicable. 
  



33 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



34 

Package leaflet: Information for the user 
 

TOOKAD 183 mg powder for solution for injection 
TOOKAD 366 mg powder for solution for injection 

padeliporfin 
 

This medicine is subject to additional monitoring. This will allow quick identification of new 
safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you are given this medicine because it contains important 
information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What TOOKAD is and what it is used for  
2. What you need to know before TOOKAD is used 
3. How TOOKAD is used 
4. Possible side effects  
5. How TOOKAD is stored  
6. Contents of the pack and other information 
 
 
1. What TOOKAD is and what it is used for 
 
TOOKAD is a medicine that contains padeliporfin (as potassium salt). It is used to treat adult men 
who have low-risk, localised prostate cancer in only one lobe, using a technique called 
Vascular-Targeted Photodynamic (VTP) therapy. The treatment is carried out under general 
anaesthetic (medicines that send you to sleep to prevent pain and discomfort). 
 
Hollow needles are used to insert the fibres into the right place in the prostate. Once it has been given, 
TOOKAD has to be activated by laser light shone along a fibre that targets the light onto the cancer. 
The activated medicine then causes the death of the cancer cells. 
 
 
2. What you need to know before TOOKAD is used  
 
TOOKAD must not be used if: 
- You are allergic to padeliporfin or any of the other ingredients of this medicine (listed in 

section 6). 
- You have undergone a procedure for treating benign prostatic hypertrophy including 

Trans-Urethral Resection of the Prostate (TURP). 
- You are having or have previously had any treatment for prostate cancer. 
- You have been diagnosed with a problem with the liver called cholestasis. 
- You are having an exacerbation of rectal inflammatory bowel disease. 
- You are not able to have general anaesthesia or invasive procedures.  
 
Warnings and precautions 
TOOKAD should only be used by personnel trained in the VTP procedure. 
 
Talk to your doctor or nurse if:  
- You feel any irritation of the skin or problems with vision or eye irritation after the 

VTP procedure. 



35 

- You experience difficulties in getting or maintaining an erection. 
- You feel any abnormal pain after the VTP procedure. 
- You have a history of a narrowing of the urethra or urinary flow problems. 
- You experience involuntary passing of urine after the VTP procedure. 
- You have had an active inflammatory bowel disease or any condition that may increase the risk 

of causing abnormal connection between the rectum and the urethra (recto-urethral fistula). 
- You have abnormal blood clotting. 
- You have a reduced kidney function or if you follow a potassium restricted diet. 
 
To date information beyond two years after VTP procedure is limited and so, at this time, data are 
currently not available to know whether the benefit of TOOKAD-VTP is long-lasting. 
 
If you do require further treatment, at the moment, there is limited information on whether 
TOOKAD-VTP affects the efficacy and safety results of other treatments (such as surgery to remove 
the prostate or radiotherapy). 
 
Photosensitivity 
Strong light may cause skin reactions and eye discomfort while TOOKAD is in the blood stream. 
 
For the 48 hours after the procedure you should avoid exposure to direct sunlight (including through 
windows) and all bright light sources, both indoors and outdoors. This includes sunbeds, bright 
computer monitor screens (see precautions below), and examination lights from medical equipment. 
 
Sunscreen creams do not protect you against the type of light (near infra-red) that can cause 
problems after the procedure. 
 
If you feel skin or eye discomfort while in hospital, you must tell your doctor or nurse so the level of 
lighting can be reduced and extra care can be taken to protect you from artificial and natural light. 
 
First 12 hours after VTP procedure 
After the procedure, you should wear protective goggles and will be kept under medical surveillance 
for at least 6 hours in a room with reduced light. 
Your medical team will decide if you can leave hospital on the evening of your treatment. You may 
need to stay overnight if you have not fully recovered from the general anaesthetic and depending on 
your condition. 
You must remain under reduced light conditions, without exposing your skin and your eyes to 
daylight. Only use light bulbs with a maximum power of 60 watts (for an incandescent light bulb) or 
6 watts (for LED lights), or 12 watts (for fluorescent low-energy lights). You may watch television at 
a distance of 2 metres and, from 6 hours after the procedure, you may use electronic devices such as 
smartphones, tablets and computers. In case you need to go out during the day, you must wear 
protective clothing and high-protection goggles to shield your skin and eyes. 
 
12-48 hours after VTP procedure 
You may go outdoors during daylight hours but only in shaded areas or when it is overcast. You 
should wear dark clothes and take care to protect your hands and face from the sun. 
 
When 48 hours have passed after the procedure, you can resume your normal activities and you can be 
exposed to direct sunlight. 
 
No patients with light-sensitive conditions such as porphyria, a history of sensitivity to sunlight or a 
history of photosensitive dermatitis have received TOOKAD in clinical studies. However, the short 
duration of action of TOOKAD means that the risk of enhanced phototoxicity is expected to be low 
provided the precautions against light exposure are stricly followed. 
 
There could be an additional risk of eye photosensitivity in patients who have received intra-occular 
anti-VEGF (medicines used to prevent new blood vessel growth) therapy. If you have received prior 
VEGF therapy, you should take particular care to protect your eyes from light for 48 hours post 



36 

TOOKAD injection. Concomitant use of systemic VEGF inhibitors is not recommended with 
TOOKAD. 
 
See also under “Other medicines and TOOKAD” for photosensitizing medicines. 
 
Difficulties in getting or maintaining an erection 
Some difficulties in getting or maintaining an erection is possible soon after the procedure and may 
last for more than 6 months. 
 
Risk of damage near the prostate gland 
Because the fibres that carry the light have to be inserted in such a way that the whole of the lobe of 
the prostate gland gets exposed, it is possible that some damage may occur outside of the prostate. 
Normally this is just the fat around the prostate and is not important but nearby organs such as the 
bladder and rectum may potentially be affected. This is normally avoidable by careful planning but 
should it occur there is a risk of an abnormal connection forming between the rectum and the bladder 
or skin. This is very rare. 
 
Problem associated with the urethra 
If you have a history of a narrowing of the urethra or urinary flow problems, treatment may increase 
the risk of poor flow and urinary retention. 
 
Urinary incontinence 
Short-term urinary incontinence has been observed and may result from urinary tract infection or from 
urgency caused by irritation to the urethra from the procedure. The condition gets better on its own or 
with treatment of the infection. 
 
Active inflammatory bowel disease 
If you have had an active inflammatory bowel disease or any condition that may increase the risk of 
causing abnormal connection between the rectum and the urethra (recto-urethral fistula), the treatment 
should be given only after careful evaluation. 
 
Abnormal clotting 
Patients with abnormal clotting may bleed excessively from the insertion of the needles required to 
position the fibres that guide the laser light. This may also cause bruising, blood in the urine and/or 
local pain. Abnormal clotting is not expected to affect how well the treatment works ; however, it is 
recommended that drugs that affect clotting are stopped prior to and for the immediate period 
following the VTP procedure. 
 
See also under “Other medicines and TOOKAD” for the effects of anticoagulants and antiplatelet 
medicines. 
 
Patients on a controlled potassium diet 
This medicine contains potassium. In general, the dose of TOOKAD contains less than 1 mmol 
(39 mg) potassium, i.e. essentially ‘potassium free’. However, patients weighing more than 115 kg 
will receive more than 1 mmol potassium. This should be taken into consideration by patients with 
reduced kidney function or patients on a controlled potassium diet where a rise in serum potassium 
would be considered detrimental. 
 
Children and adolescents 
This medicine should not be given to children and adolescents less than 18 years of age. 
 
Other medicines and TOOKAD 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines, including medicines obtained without a prescription. Some medicines (in particular any 
medicines that are photosensitising or that affect blood clotting) may interact with TOOKAD and 
should be stopped before using TOOKAD. You may also be required to not take certain medicines for 



37 

several days after the VTP procedure. Your doctor will also advise what medicines may be substituted 
where appropriate and when these medicines can be re-started after the VTP procedure. 
 
The following types of medicines may be ones that your doctor will advise you to stop temporarily: 
 
Medicines with a potentially photosensitising effect: 
- Certain antibiotics used to treat infection (tetracyclines, sulphonamides, quinolones). 
- Certain medicines used to treat psychiatric conditions (phenothiazines). 
- Certain medicines used in type II diabetes (hypoglycaemic sulphonamides). 
- Certain medicines used for hypertension, oedema, heart failure or renal failure (thiazide 

diuretics). 
- A medicine used to treat fungal infections (griseofulvin). 
- A medicine used to treat cardiac arrhythmia (amiodarone). 
 
These medicines 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 medicine (such as amiodarone), increased sensitivity may 
occur, you may need to protect yourself from direct light exposure for a longer period. 
 
Anticoagulants (medicines that prevent the blood from clotting) 
These medicines (e.g. acenocoumarol, warfarin) should be stopped at least 10 days before the VTP 
procedure with TOOKAD. 
 
Antiplatelet agents (medicines that decrease platelet aggregation (stickiness) in the blood and reduce 
clotting) 
These medicines (e.g. acetylsalicylic acid) should be stopped at least 10 days before the VTP 
procedure with TOOKAD and re-started at least 3 days after the procedure. 
 
Other medicines that may interact with TOOKAD 
The use of medicines such as repaglinide, atorvastatin, pitavastatin, pravastatin, rosuvastatin, 
simvastatin, bosentan, glyburide should be avoided on the day of TOOKAD administration and for at 
least 24 hours after administration. 
 
Contraception 
You or your partner or both should use an effective form of birth control to prevent your partner 
getting pregnant for 90 days after the VTP procedure. Check with your doctor about the birth control 
methods to use and how long to use them for. If your partner becomes pregnant within three months of 
your treatment, you must immediately tell your doctor. 
 
Pregnancy and breast-feeding 
TOOKAD is not indicated for the treatment of women. 
 
Driving and using machines 
TOOKAD has no influence on the ability to drive or use machines. However, as the procedure 
includes general anaesthesia, you should not perform complex tasks like driving or using machines 
until 24 hours after a general anaesthetic is used. 
 
 
3. How TOOKAD is used 
 
TOOKAD is restricted to hospital use only. It should only be used by personnel trained in the 
VTP procedure. 
 
Dose 
The recommended dose of TOOKAD is one single dose of 3.66 mg per kg of body weight, injected 
into a vein. The injection lasts 10 minutes. 



38 

For instructions to healthcare professionals on reconstitution of TOOKAD before injection, see 
“Reconstitution of the TOOKAD powder for solution for injection”. 
 
Only the lobe that contains the cancer will be treated. Additional VTP procedures of the prostate are 
not recommended. 
 
VTP procedure 
The day before and at the beginning of the VTP procedure, a rectal preparation is performed in order 
to clean the rectum. Your doctor may prescribe antibiotics to prevent infection and alpha-blockers 
(medicines given to prevent difficulties in urinating). You will be given a general anaesthetic to send 
you to sleep before the VTP procedure. Fibres to carry the laser light are inserted into the prostate 
gland by using hollow needles. TOOKAD is activated immediately after injection by shining light 
through the fibres from a connected laser device. 
 
If you have any questions on the use of this medicine, ask your doctor, your pharmacist or your nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
In addition, inserting needles into the prostate gland and inserting a urinary catheter for the procedure 
may be associated with further side effects. 
 
Possible side effects can occur with TOOKAD and VTP procedure. 
 
If you get any of the side effects below, tell your doctor immediately: 
- Urinary retention (not able to pass urine). In the few days after the VTP procedure some patients 

may have difficulties (poor stream due to urethral narrowing) or inability to pass urine. This 
may necessitate inserting a catheter inside your bladder through the penis and the catheter will 
remain in place for a few days or weeks to drain the urine. 

- Fever, pain and swelling in the area of the operation might occur after the procedure. These may 
be signs of infection in the urinary tract, the prostate or the genital system. In this case, you 
should contact your doctor as you may need further blood or urine analysis and antibiotics 
treatment. These infections are usually easily treated. 

 
In addition to the side effects listed previously, other side effects can occur. 
 
Very common side effects (may affect more than 1 in 10 people) 
- Problems with or pain on passing urine (including pain or discomfort on passing urine, bladder 

pain, the need to pass urine urgently or more frequently or at night; involuntary passing of 
urine), 

- Sexual problems (including difficulty in getting or maintaining an erection, ejaculation failure, 
loss of desire or pain on intercourse), 

- Blood in the urine (haematuria), 
- Perineal injury including bruising in the skin, bruising near where the needles are put into the 

prostate, pain and tenderness, 
- Genital pain and discomfort (inflammation of the testicles or the epididymis, pain due to 

inflammation or fibrosis of the prostate). 
 
Common side effects (may affect up to 1 in 10 people)  
- Anorectal discomfort (discomfort near the anus and just inside the anus), haemorrhoids (piles), 

proctalgia (pain in the anal region), 
- Problems with bowels (including diarrhoea or occasional soiling), 
- General and musculoskeletal pain (muscle/bony pain, pain in the end of the limbs, back pain or 

bleeding into the joints), 
- Haematospermia (presence of blood in the ejaculate), 
- High blood pressure, 



39 

- Increases in blood lipids, lactate dehydrogenase increased, white blood cell increased, creatine 
phosphokinase increased, potassium decreased, prostatic specific antigen (PSA) increased, 

- Skin reaction, erythema (reddening), rash, dryness, pruritus, depigmentation, 
- Abnormal blood tests related to coagulation, 
- Discomfort in the abdominal region, 
- Fatigue (tiredness). 
 
Uncommon side effects (may affect up to 1 in 100 people) 
- Dizziness, fall, 
- Headache,  
- Sensory disturbance, formication (sensation like crawling insects on or under the skin), 
- Eye irritation, photophobia (intolerance to light), 
- Dyspnoea exertional (excessive shortness of breath during or after exercise), 
- Mood disorder, 
- Weight decreased.  
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How TOOKAD is stored 
 
You will not have to store this medicine. This medicine is stored under the responsibility of the 
specialist.  
 
The following information is intended for the specialist only. 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use after the expiry date which is stated on the shield label after “EXP”. The expiry date refers 
to the last day of that month. 
 
Store in a refrigerator (2°C-8°C). 
Store in the outer carton in order to protect it from light. 
 
Any unused medicine or waste material should be disposed of in accordance with local requirements. 
 
 
6. Contents of the pack and other information 
 
What TOOKAD contains  
- The active substance is padeliporfin. 

Each vial of TOOKAD 183 mg contains 183 mg of padeliporfin (as potassium salt). 
Each vial of TOOKAD 366 mg contains 366 mg of padeliporfin (as potassium salt). 

 1 mL of reconstituted solution contains 9.15 mg of padeliporfin. 
 

- The other ingredient is mannitol. 
 
What TOOKAD looks like and contents of the pack 
TOOKAD is a dark powder. 
 
Each carton of TOOKAD 183 mg powder for solution for injection contains an amber glass vial with a 
blue cap. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


40 

Each carton of TOOKAD 366 mg powder for solution for injection contains an amber glass vial with a 
white cap. 
 
Marketing Authorisation Holder 
Steba Biotech S.A. 
7 Place du Théâtre 
L-2613 Luxembourg 
Luxembourg 
 
Manufacturer 
LIOF-PHARMA S.L. 
c/ Hermanos Lumiere 5 
Parque Tecnológico Miñano 
01510 Alava 
Spain 
 
This leaflet was last revised in <{MM/YYYY}>. 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
------------------------------------------------------------------------------------------------------------------------ 
 
The following information is intended for healthcare professionals only: 
 
Reconstitution of the TOOKAD powder for solution for injection 
The solution must be prepared in a dimmed-light environment due to the photosensitizing properties of 
the medicine. 
1. Reconstitute the solution by adding: 
 - for TOOKAD 183 mg: 20 mL of a 5 % glucose solution in the vial containing the powder; 
 - for TOOKAD 366 mg: 40 mL of a 5 % glucose solution in the vial containing the powder. 
2. Swirl the vial gently for 2 minutes. The final solution concentration is 9.15 mg/mL. 
3. Allow the vial to rest in a vertical position for 3 minutes without further shaking or moving. 
4. Transfer the contents of the vial into an opaque syringe. 
5. Allow the opaque syringe to rest in a vertical position for 3 minutes to ensure any foam 

disappears. 
6. Place a 0.22 μm injection filter on the syringe. 
7. Connect an opaque tube to the filter. 
 
The reconstituted solution for infusion is dark. 
 
Illumination for photoactivation of TOOKAD 
TOOKAD is locally activated immediately after injection by laser light at 753 nm delivered via 
interstitial optical fibres from a laser device at a power of 150 mW/cm of fibre, delivering an energy of 
200 J/cm over 22 minutes 15 seconds. 
Planning of optical fibre positioning should be performed at the beginning of the procedure using the 
treatment guidance software. During the procedure, the optical fibres are selected and positioned 
transperineally into the prostate gland under ultrasound guidance to achieve a Light Density Index 
(LDI) ≥ 1 in the targeted tissue. 
 
Storage conditions 
Store in a refrigerator (2°C-8°C). 
Keep the vial in the outer carton in order to protect from light. 
 



41 

After reconstitution with a 5 % glucose solution in its vial, the chemical and physical stability of 
TOOKAD has been demonstrated for 8 hours at 15°C-25°C and at 5°C ± 3°C. From a microbiological 
point of view, the product should be used immediately. If not used immediately, in-use storage times 
and conditions prior to use are the responsibility of the user. 
 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET