TOOKAD: Uses, Dosage and Side Effects

What is TOOKAD and what is it used for?

TOOKAD (padeliporfin) is a photosensitising medicine used in vascular-targeted photodynamic therapy (VTP) to treat adult men with previously untreated, unilateral, low-risk localised prostate cancer. The drug is given as a single intravenous infusion and then activated by laser light inside the prostate, causing selective destruction of tumour blood vessels while preserving urinary and sexual function in most patients.

TOOKAD is the brand name for padeliporfin di-potassium, a water-soluble derivative of bacteriochlorophyll isolated from photosynthetic bacteria. It belongs to a class of medicines known as photosensitisers — drugs that are therapeutically inactive on their own but generate cytotoxic reactive oxygen species when they are activated by light of a specific wavelength. Padeliporfin is activated by near-infrared laser light at 753 nm, a wavelength that penetrates several centimetres of soft tissue, allowing controlled treatment of deep-seated organs such as the prostate.

Unlike most earlier photosensitisers, which accumulate inside tumour cells and require hours or days before they can be activated, padeliporfin remains almost exclusively within the vascular compartment and is cleared from plasma within a few hours. Illumination therefore occurs while the drug is still circulating in the prostate vessels — a concept known as vascular-targeted photodynamic therapy (VTP). Activation triggers rapid thrombosis, ischaemic necrosis and tumour apoptosis within the treated volume, without widespread damage to the surrounding tissue.

TOOKAD received a centralised European marketing authorisation in 2017 for men with previously untreated, unilateral, low-risk, localised adenocarcinoma of the prostate who have a life expectancy greater than 10 years and whose cancer meets all of the following criteria: clinical stage cT1c or cT2a, Gleason pattern 3 (Gleason score of 6), prostate-specific antigen (PSA) ≤10 ng/mL, and at most three positive cancer cores with maximum cancer core length of 5 mm in any one core, or a single positive core with 50% or less cancer involvement. Additional eligibility criteria, including prostate volume and anatomy, are assessed by the treating urologist.

TOOKAD is used when a man and his clinicians wish to consider a tissue-preserving ("focal") treatment option that lies between active surveillance and radical therapy. By selectively ablating a single prostate lobe, VTP aims to control the index lesion while preserving continence and erectile function better than whole-gland treatments. It does not replace active surveillance for the lowest-risk disease, and it is not intended for intermediate- or high-risk prostate cancer.

How does padeliporfin work?

Padeliporfin is a palladium bacteriopheophorbide derivative. When a molecule of padeliporfin absorbs a photon of 753 nm light, it becomes temporarily excited and transfers this extra energy to surrounding molecular oxygen. The reaction produces reactive oxygen species (ROS) — primarily superoxide, hydroxyl radicals and hydrogen peroxide — which damage the endothelial lining of the tumour vasculature within seconds. The damaged endothelium exposes tissue factor, triggering platelet activation, rapid thrombus formation and occlusion of the treated vessels. The resulting ischaemic hypoxia leads to necrosis and apoptosis of the surrounding tumour tissue over the following 24 to 72 hours.

Clinical evidence and place in therapy

The pivotal evidence comes from the phase 3 CLIN1001 PCM301 study, a randomised controlled trial published in The Lancet Oncology in 2017 that compared TOOKAD-VTP with active surveillance in 413 men with low-risk localised prostate cancer. At 24 months, disease progression occurred in 28% of men in the VTP group versus 58% in the active surveillance group, and the need for radical therapy was 24% versus 53%. Negative biopsy rates at 24 months were 49% versus 14%, in favour of TOOKAD. Extended follow-up has continued to show durable benefit. International guidelines, including those of the European Association of Urology (EAU), position VTP with padeliporfin as an option for carefully selected low-risk patients who wish to avoid both immediate radical therapy and ongoing surveillance anxiety.

What should you know before taking TOOKAD?

Before TOOKAD is used, your urologist and anaesthetist will review your medical history, current medications, prostate anatomy and overall fitness for surgery. You should disclose any allergies, previous prostate or pelvic surgery, photosensitivity disorders, clotting problems and use of anticoagulants. TOOKAD is not suitable for men with a history of pelvic radiotherapy, inflammatory rectal disease, or known hypersensitivity to padeliporfin.

Because TOOKAD is delivered as part of a combined pharmacological-and-laser procedure under general or spinal anaesthesia, the safety assessment is broader than for a conventional tablet. Eligibility is determined jointly by the urologist performing VTP, the anaesthetist and (for older men or those with significant comorbidity) the relevant medical specialists. A thorough review of concomitant medicines is essential, as several classes of drugs can influence photosensitivity, coagulation or wound healing.

You will also be given detailed written instructions about light avoidance for the 48 hours that follow the procedure. This short window reflects the rapid plasma clearance of padeliporfin and differs substantially from the weeks-long restrictions imposed by first-generation photosensitisers such as porfimer sodium.

Contraindications

TOOKAD must not be used in any of the following circumstances:

• Known hypersensitivity to padeliporfin di-potassium or to any of the listed excipients (mannitol, sodium hydroxide)
• Previous prostate surgery or procedures that would interfere with the transperineal placement of optical fibres (for example, a history of transurethral resection of the prostate may be a relative contraindication depending on anatomy)
• Previous pelvic radiotherapy for any indication
• Active inflammatory disease of the rectum, rectal fistula or significant anatomical abnormalities that prevent safe placement of the laser fibres
• Porphyrias or other conditions causing severe cutaneous photosensitivity
• Severe uncontrolled coagulopathy or inability to interrupt anticoagulation safely before the procedure

Warnings and precautions

Although TOOKAD-VTP is considered minimally invasive, it is a hospital-based interventional procedure and all its risks must be weighed against the generally indolent course of low-risk prostate cancer.

Light sensitivity. Patients remain photosensitive for a short period after administration. You must stay in a dimly lit room for several hours following the procedure and avoid direct sunlight for at least 48 hours. Window glass does not provide sufficient protection; if outdoor travel home is necessary, covered clothing, gloves, wide-brimmed hats and tinted sunglasses are recommended. Indoor normal room lighting (≤200 lux) is acceptable. Full recovery of normal light tolerance is expected within 48 hours.

Urological complications. Transient dysuria, haematuria, urinary retention and urinary incontinence are common in the weeks following the procedure. A urinary catheter is typically placed at the end of VTP and left in situ for several days. Rarely, more serious urological complications such as rectourethral fistula have been reported; risk factors include anatomical variations and prior pelvic surgery.

Sexual function. Erectile dysfunction and ejaculatory disorders are frequently reported in the early post-procedure period, but the majority of men recover pre-treatment function within 6 to 12 months. Pre-existing erectile dysfunction, age and diabetes are the principal predictors of persistent impairment.

Hypertension. Blood pressure commonly rises during infusion and laser activation, probably reflecting the vascular effects of padeliporfin. Blood pressure is monitored continuously during the procedure and treated intraoperatively if needed.

Follow-up biopsy. A mandatory prostate biopsy is performed 12 months after VTP to document oncological outcome and guide further management. Patients must be willing and able to comply with this and with regular PSA follow-up.

Pregnancy and breastfeeding

TOOKAD is indicated in adult men only, so direct use in pregnancy or during breastfeeding is not applicable. No clinical data exist on the effects of padeliporfin on male fertility or on sperm in the short period after treatment. Although systemic exposure falls to negligible levels within a few hours, men are routinely advised to discuss contraception and family planning with their urologist if pregnancy is being considered in the months following VTP.

Driving, machinery and daily activities

Because TOOKAD is administered under anaesthesia, you must not drive or operate machinery on the day of the procedure. Most men resume light activities within 2 to 3 days and return to work within 1 to 2 weeks, depending on occupation and urinary catheter status.

How does TOOKAD interact with other drugs?

The most clinically relevant interactions with TOOKAD involve other photosensitising medicines (which can increase skin reactions if light exposure occurs) and anticoagulants or antiplatelet drugs (which can increase procedural bleeding and haematoma). Because padeliporfin is cleared rapidly and is not a major substrate, inducer or inhibitor of cytochrome P450 enzymes, systemic pharmacokinetic interactions are uncommon.

Before the procedure, the hospital pharmacist and the treating urologist will review all of your medicines — prescription, over-the-counter and herbal — and may ask you to pause specific drugs temporarily. Examples include anticoagulants (warfarin, direct oral anticoagulants such as apixaban or rivaroxaban) and some antiplatelet agents; these are stopped or bridged according to local perioperative protocols. St John's Wort and other herbal photosensitisers should also be disclosed.

Major interactions

Minor interactions

Padeliporfin is not metabolised by the cytochrome P450 system to any clinically significant extent and is not a substrate, inhibitor or inducer of the major drug transporters. Therefore, most commonly prescribed medicines — including antihypertensives, statins, antidiabetic agents and 5-alpha-reductase inhibitors — can be continued without dose adjustment. Strong CYP3A inhibitors and inducers have not been shown to alter padeliporfin exposure in clinical studies, but routine monitoring is still advised in patients taking multiple medicines.

Alcohol has no specific interaction with padeliporfin, but general perioperative advice applies: avoid heavy alcohol consumption in the 24 hours before anaesthesia, and resume alcohol cautiously after any opioid analgesia required for post-procedural discomfort.

What is the correct dosage of TOOKAD?

The recommended dose of TOOKAD is 4 mg per kilogram of body weight, given as a single 10-minute intravenous infusion. Immediately after the infusion ends, the prostate is illuminated for 22 minutes and 15 seconds with 753 nm laser light delivered through optical fibres inserted through the perineum under transrectal ultrasound guidance. The entire procedure is performed in an operating theatre under general or spinal anaesthesia and is not repeated unless clinically indicated.

TOOKAD is not a daily medicine. A single administration forms part of a one-time interventional procedure performed by a urologist trained in VTP, and the dose is calculated individually on the basis of the patient's body weight. The drug is reconstituted from a 200 mg vial of powder with 20 mL of sterile water to give a solution containing 10 mg/mL of padeliporfin. The calculated volume is then infused into a peripheral or central vein over 10 minutes using an infusion pump.

Laser fibres — typically four to six per lobe — are placed transperineally into the prostate under biplanar transrectal ultrasound and template guidance. Illumination begins at the end of the infusion and delivers a total energy of approximately 200 J/cm along each fibre, at a power of 150 mW/cm, for a standard duration of 22 minutes and 15 seconds. Real-time dosimetry ensures that the entire treatment volume receives adequate light exposure.

Adults

Children and adolescents

Older adults

Renal and hepatic impairment

Missed dose

Overdose

What are the side effects of TOOKAD?

Most side effects of TOOKAD are urological and occur in the first weeks after the procedure. The most common (affecting more than 1 in 10 men) include perineal pain, painful urination, blood in the urine, erectile dysfunction and urinary retention. Serious adverse effects such as rectourethral fistula and severe phototoxic reactions are rare when patients follow the light-avoidance instructions. In pivotal trials no treatment-related deaths were reported.

Adverse effects are classified according to European Medicines Agency (EMA) frequency conventions: very common (≥1/10), common (1/100 to 1/10), uncommon (1/1 000 to 1/100), rare (1/10 000 to 1/1 000) and very rare (<1/10 000). Most reactions below are transient and resolve within weeks; when longer-term outcomes are known, these are noted.

Long-term (beyond 12 months) urinary and sexual outcomes are being tracked in ongoing registries. In the PCM301 study, quality-of-life scores returned to baseline in the majority of patients within 12 months, and International Index of Erectile Function (IIEF) scores showed gradual recovery. Patients should report persistent or worsening urinary, sexual or bowel symptoms to their urologist for assessment.

How should TOOKAD be stored?

TOOKAD vials are stored by the hospital pharmacy in a refrigerator at 2–8 °C, protected from light and in the original carton. Reconstituted solution should be used immediately and protected from light during infusion. Because TOOKAD is hospital-only, patients do not handle or store the medicine themselves.

Key storage requirements documented in the EMA Summary of Product Characteristics are as follows:

• Unopened vials: store in a refrigerator at 2 °C to 8 °C in the original carton to protect from light. Do not freeze.
• Shelf life: 3 years in the original, unopened packaging (exact expiry date is printed on the carton).
• After reconstitution: the prepared solution should be used immediately. If immediate use is not possible, it may be stored in the original vial, protected from light, for no more than 2 hours at 2 °C to 8 °C and should be administered within 30 minutes of being removed from the refrigerator.
• During infusion: the infusion line and any visible part of the syringe or vial should be shielded from direct light (for example, using the provided protective sleeve or wrapping in aluminium foil).
• Disposal: any unused product and equipment exposed to padeliporfin is classified as hazardous waste and disposed of according to local hospital cytotoxic-waste procedures.

Why light protection matters

Padeliporfin is designed to be activated by visible and near-infrared light. Exposure to ambient light before administration could pre-activate the drug, generate reactive oxygen species inside the vial and reduce clinical effectiveness. Ceiling-mounted surgical lights are fitted with 753 nm–compatible shielding during the procedure, and the hospital pharmacy follows strict protocols to keep vials in light-protective containers until the moment of use.

What does TOOKAD contain?

Each 200 mg vial of TOOKAD contains padeliporfin di-potassium as the active substance, together with mannitol (a bulking agent) and sodium hydroxide or hydrochloric acid for pH adjustment. The powder is reconstituted with 20 mL of sterile water for injection to give a solution of 10 mg/mL padeliporfin. No preservatives, lactose or gluten are present.

Active substance

• Padeliporfin di-potassium — 200 mg per vial (corresponding to 183 mg of padeliporfin free acid). Chemical class: palladium bacteriopheophorbide derivative.

Excipients

• Mannitol — acts as a bulking agent to stabilise the lyophilised powder
• Sodium hydroxide — used for pH adjustment during manufacture
• Hydrochloric acid — used for pH adjustment during manufacture

Appearance and packaging

TOOKAD is supplied as a dark-coloured, lyophilised powder in a colourless glass vial with a rubber stopper and aluminium seal. Each carton contains a single vial. After reconstitution with sterile water for injection, the solution is a dark green to dark brown clear liquid that is sensitive to light.

Packaging and excipient warnings

TOOKAD contains negligible amounts of sodium (less than 1 mmol per dose) and is therefore considered essentially "sodium-free". The product does not contain lactose, gluten, starch, alcohol or common allergens of concern. Patients with known hypersensitivity to any excipient should inform their urologist.