IMLYGIC Solution for injection Ref.[7652] Active ingredients: Talimogene laherparepvec

Treatment with talimogene laherparepvec should be initiated and supervised by a qualified physician experienced in the treatment of cancer.

Patients treated with Imlygic must be given the patient alert card and be informed about the risks of Imlygic (see also package leaflet).

Posology

Imlygic is provided in single use vials of 1 mL each in two different concentrations:

• 10⁶ (1 million) PFU/mL – For initial dose only.
• 10⁸ (100 million) PFU/mL – For all subsequent doses.

The total injection volume for each treatment visit should be up to a maximum of 4 mL. The initial recommended dose is up to a maximum of 4 mL of Imlygic at a concentration of 10⁶ (1 million) PFU/mL. Subsequent doses should be administered up to 4 mL of Imlygic at a concentration of 10⁸ (100 million) PFU/mL.

The recommended dosing schedule for Imlygic is shown in table 1.

Table 1. Recommended dosing schedule for Imlygic:

Determining Imlygic dose volume (per lesion)

The volume of Imlygic to be injected into each lesion is dependent on the size of the lesion and should be determined according to table 2. The total injection volume for each treatment session should be up to a maximum of 4 mL.

Table 2. Selection of Imlygic injection volume based on lesion size:

Patients may experience increase in size of existing lesion(s) or the appearance of a new lesion prior to achieving a response. As long as there are injectable lesion(s) remaining, Imlygic should be continued for at least 6 months unless the physician considers that the patient is not benefitting from Imlygic treatment or that other treatment is required.

Imlygic treatment may be reinitiated if new lesions appear following a complete response and the physician considers that the patient will benefit from treatment.

Special populations

Paediatric population

The safety and efficacy of Imlygic in paediatric patients has not been established. No data are available.

Elderly population

No adjustment of the dose is required in patients ≥65 years old (see section 5.1).

Hepatic and renal impairment

No clinical studies have been conducted to evaluate the effect of hepatic or renal impairment on the pharmacokinetics of talimogene laherparepvec. However, no adjustment in dosage is necessary for patients with hepatic or renal impairment.

Method of administration

Imlygic is to be administered by intralesional injection into cutaneous, subcutaneous, and/or nodal lesions that are visible, palpable or detectable by ultrasound guidance.

If healthcare professionals are accidentally exposed to Imlygic, see sections 4.4 and 6.6.

Healthcare professionals who are immunocompromised or pregnant should not administer Imlygic and should not come into direct contact with the Imlygic injection site(s) or body fluids of treated patients (see sections 4.3 and 4.4).

Follow the instructions below to prepare and administer Imlygic to patients:

Pre-injection:

• Thaw Imlygic vial(s) at room temperature. Thawed Imlygic may be stored prior to administration (see section 6.3).
• Draw the desired amount of Imlygic from the vial into a syringe using aseptic technique. A 22- to 26-gauge needle is recommended.
• The injection site may be treated with a topical anaesthetic agent. Injectable anaesthetic may be injected around the periphery of the lesion but should not be injected directly into the lesion.
• Clean the lesion and surrounding areas with an alcohol swab and let dry.

Injection:

• Inject Imlygic intralesionally into cutaneous, subcutaneous, and/or nodal lesions that are visible, palpable or detectable by ultrasound guidance.
• Determine injection volume for each lesion using table 2 above.
• Using a single insertion point, inject Imlygic along multiple tracks as far as the radial reach of the needle allows within the lesion to achieve even and complete dispersion. Multiple insertion points may be used if a lesion is larger than the radial reach of the needle.

Figure 1. Injection administration for cutaneous lesions:

Figure 2. Injection administration for subcutaneous lesions:

Figure 3. Injection administration for nodal lesions:

• Disperse Imlygic evenly and completely within the lesion by pulling the needle back without exiting the lesion. Redirect the needle as many times as necessary while injecting the remainder of the dose of Imlygic. Continue until the full dose is evenly and completely dispersed.
• When removing the needle, withdraw it from the lesion slowly to avoid leakage or splash back of Imlygic at the insertion point.
• Repeat these steps for other lesions that need to be injected. Use a new needle anytime the needle is completely removed from a lesion and each time a different lesion is injected.

Post-injection:

• Apply pressure to the injection site with a sterile gauze for at least 30 seconds.
• Swab the injection site and surrounding area with alcohol, and cover the injected lesion with an absorbent pad and dry occlusive dressing.

Disposal:

Dispose of all materials that have come in contact with Imlygic (e.g. vial, syringe, needle, any cotton or gauze) in accordance with local institutional procedures (see section 6.6).

There is no clinical experience with overdose with Imlygic. Doses up to 4 mL at a concentration of 10⁸ PFU/mL every 2 weeks have been administered in clinical trials with no evidence of dose limiting toxicity. The maximum dose of Imlygic that can be safely administered has not been determined. In the event of a suspected overdose or inadvertent intravenous administration, the patient should be treated symptomatically, e.g. with acyclovir or other anti-viral agents (see section 4.4) and supportive measures instituted as required.

Shelf life

Unopened vial: 5 years.

Thawing Imlygic vials:

• Before use, thaw frozen Imlygic vials at room temperature (20°C to 25°C) until Imlygic is liquid (approximately 30 minutes). Gently swirl. Do NOT shake.
• Vials should be thawed and stored in the original carton until administration in order to protect from light.

After thawing:

• After thawing, administer Imlygic as soon as practically feasible.
• Thawed Imlygic is stable when stored at temperatures of 2°C up to 25°C protected from light in its original vial, in a syringe, or in the original vial followed by a syringe. Do not exceed the storage times specified in table 7 and table 8.
• If storing thawed Imlygic in the original vial followed by a syringe:
  • the same temperature range should be maintained throughout the duration of storage until administration.
  • the storage time in the syringe at ambient temperature up to 25°C cannot exceed 2 hours for 10⁶ (1 million) PFU/mL and 4 hours for 10⁸ (100 million) PFU/mL (see table 7).
  • the maximum cumulative storage time (storage time in vial plus storage time in syringe) cannot exceed the durations in table 8.
• Imlygic must not be refrozen once it has thawed. Discard any thawed Imlygic in the vial or syringe stored longer than the specified times below.

Table 7. Maximum storage time for thawed Imlygic in syringe:

Table 8. Maximum cumulative storage time (storage time in vial plus storage time in syringe) for thawed Imlygic:

Store and transport frozen (-90°C to -70°C).

Store in the original carton in order to protect from light.

Imlygic is provided as a one ml preservative-free solution in a single–use vial (cyclic olefin polymer plastic resin) with stopper (chlorobutyl elastomer) and seal (aluminium) with flip-off cap (polypropylene) in two different presentations:

Figure 6. Single-use vial permanently inserted into a clear copolyester plastic sleeve:

OR

Figure 7. Single-use vial without a clear plastic sleeve:

The vial cap is colour coded: 10⁶ (1 million) PFU/mL is light green and 10⁸ (100 million) PFU/mL is royal blue.

Follow local institutional guidelines for handling and administration, personal protective equipment, accidental spills, and waste disposal.

• Wear protective gown or laboratory coat, safety glasses, or face shield and gloves while preparing or administering Imlygic. Cover any exposed wounds before administering. Avoid contact with skin, eyes or mucous membranes.
• After administration, change gloves prior to applying occlusive dressings to injected lesions. Wipe the exterior of occlusive dressing with an alcohol wipe. It is recommended to keep injection sites covered with airtight and watertight dressings at all times, if possible. To minimise the risk of viral transmission, patients should keep their injection site covered for at least 8 days from the last treatment or longer if the injection site is weeping or oozing. Advise patients to apply dressing as instructed by the healthcare professional and to replace the dressing if it falls off.
• Dispose of all materials that have come in contact with Imlygic (e.g. vial, syringe, needle, any cotton or gauze) in accordance with local institutional procedures.

Accidental exposure:

• In the event of an accidental occupational exposure to Imlygic (e.g. through a splash to the eyes or mucous membranes) during preparation or administration, flush with clean water for at least 15 minutes. In the event of exposure to broken skin or needle stick, clean the affected area thoroughly with soap and water and/or disinfectant.
• Treat all Imlygic spills with a virucidal agent and absorbent materials.
• Advise patients to place used dressings and cleaning materials in a sealed plastic bag as they may be potentially contaminated, and to dispose of the bag in household waste.

This medicine contains genetically modified organisms. Unused medicine must be disposed of in compliance with the institutional guidelines for genetically modified organisms or biohazardous waste, as appropriate.