Posology : מינונים

4.2     Posology and method of administration

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 the treatment.

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 is shown in table 1.

Table 1: Recommended dosing schedule
Maximum
Treatment      Treatment         total           Dose                Prioritization of lesions to be visit        interval       injection     concentrations                     injected volume
•      Inject largest lesion(s) first.
106        •      Prioritize injection of
Initial           -          Up to 4 mL         (1 million)           remaining lesions based on lesion size until maximum
PFU/mL injection volume is reached.
•      First inject any new lesions
(lesions that may have developed since initial
3 weeks after                           108               treatment).
Second           initial      Up to 4 mL        (100 million)   •      Prioritize injection of treatment                          PFU/mL               remaining lesions based on lesion size until maximum injection volume is reached.
All                                                           •      First inject any new lesions subsequent                                                                (lesions that may have                    2 weeks after                           108 treatment                                                                developed since previous previous      Up to 4 mL        (100 million) visits                                                                 treatment).
treatment                          PFU/mL
(including re-                                                       •      Prioritize injection of initiation)                                                              remaining lesions based on 
lesion size until maximum injection volume is reached.

Determining Imlygic dose volume (per lesion)

The volume 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

Lesion size
Imlygic injection volume
(longest dimension)
> 5 cm                                                up to 4 mL
> 2.5 cm to 5 cm                                      up to 2 mL
> 1.5 cm to 2.5 cm                                    up to 1 mL
> 0.5 cm to 1.5 cm                                    up to 0.5 mL
≤ 0.5 cm                                              up to 0.1 mL

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

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.

Pediatric population

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



Precautions to be taken before manipulating or administering the medicinal product 
This medicinal product contains genetically modified organisms. Personal protective equipment should be worn while preparing or administering talimogene laherparepvec (see section 6.6).

Healthcare professionals who are immunocompromised or pregnant should not administer Imlygic and should not come into direct contact with the 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 vials may be stored prior to administration (see section 6.3). For handling of thawed vials, see section 6.6.
•     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 anesthetic agent. Injectable anesthetic 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.

Cutaneous lesions                    Subcutaneous lesions              Nodal lesions 


Figure 1:                            Figure 2:                         Figure 3: Injection administration for         Injection administration for      Injection cutaneous lesions                    subcutaneous lesions              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 . 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.