Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Traceability
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Previously treated patients

Efficacy data for Imlygic in the current second or later line treatment settings are limited.
Immunocompromised patients

Imlygic has not been studied in immunocompromised patients. Based on animal data, patients who are severely immunocompromised may be at an increased risk of disseminated herpetic infection and should not be treated with Imlygic (see sections 4.3 and 5.3). Disseminated herpetic infection may also occur in immunocompromised patients (such as those with HIV/AIDS, leukemia, lymphoma, common variable immunodeficiency, or who require chronic high-dose steroids or other immunosuppressive agents). The risks and benefits of treatment should be considered before administering Imlygic to these patients.

Accidental exposure to Imlygic

Accidental exposure may lead to transmission of Imlygic and herpetic infection. Healthcare professionals and close contacts (e.g. household members, caregivers, sex partners or persons sharing the same bed) should avoid direct contact with injected lesions or body fluids of treated patients during the entirety of the treatment period and up to 30 days after the last treatment administration (see section 6.6). Accidental needle stick and splash-back have been reported in healthcare professionals during preparation and administration.

Close contacts who are pregnant or immunocompromised should not change the patient’s dressing or clean their injection site. Pregnant women, neonates, and immunocompromised individuals should not be exposed to potentially contaminated materials.

Healthcare professionals should ensure that patients are able to comply with the requirement to cover injection sites with occlusive dressings (see section 6.6). Patients should also be advised to avoid touching or scratching injection sites as this could lead to inadvertent transfer of Imlygic to other areas of their body or to their close contacts.

Although it is not known if Imlygic could be transmitted through sexual contact, it is known that wild-type HSV-1 can be transmitted through sexual contact. Patients should be advised to use a latex condom during sexual contact to prevent possible transmission of Imlygic. Women of childbearing potential should be advised to use an effective method of contraception to prevent pregnancy during treatment (see section 4.6).

Caregivers should be advised to wear protective gloves when assisting patients in applying or changing occlusive dressings and to observe safety precautions for disposal of used dressings and cleaning materials (see section 6.6).

In the event of an accidental exposure to Imlygic, follow instructions in section 6.6. If signs or symptoms of herpetic infection develop, they should contact their healthcare professional. In case 
suspected herpetic lesions occur, patients, close contacts or healthcare providers have the option of follow-up testing by the Marketing Authorization Holder for further characterization of the infection.

Herpetic infection in Imlygic-treated patients

In clinical studies, herpetic infections (including cold sores and herpes keratitis) have been reported in patients treated with Imlygic. Symptoms of a local or systemic infection possibly related to Imlygic are anticipated to be similar to symptoms caused by wild-type HSV-1 infections.

Individuals with wild-type HSV-1 infection are known to be at a lifelong risk for symptomatic herpetic infection due to reactivation of latent wild-type HSV-1. Symptomatic herpetic infection due to possible reactivation of Imlygic should be considered.

Patients who develop herpetic infections should be advised to follow standard hygienic practices to prevent viral transmission.

Talimogene laherparepvec is sensitive to acyclovir. The risks and benefits of Imlygic treatment should be considered before administering acyclovir or other anti-viral agents indicated for management of herpetic infection. These agents may interfere with the effectiveness of the treatment if administered systemically or topically directly to the injection site.

Information on herpetic lesions is provided in the Patient Safety Information Card.

Cellulitis at the injection site
Necrosis or ulceration of tumor tissue may occur following Imlygic treatment. Cellulitis and systemic bacterial infection have been reported. Careful wound care and infection precautions are recommended, particularly if tissue necrosis results in open wounds.

Impaired healing at the injection site

In clinical studies, impaired healing at the injection site has been reported. Imlygic may increase the risk of impaired healing in patients with underlying risk factors (e.g. previous radiation at the injection site, or lesions in poorly vascularized areas).

The risks and benefits of Imlygic should be considered before continuing treatment if persistent infection or delayed healing develops.

Immune-mediated events

In clinical studies, immune-mediated events including as glomerulonephritis, vasculitis, pneumonitis, worsening psoriasis, and vitiligo have been reported in patients treated with Imlygic.

The risks and benefits of Imlygic should be considered before initiating treatment in patients who have underlying autoimmune disease or before continuing treatment in patients who develop immune-mediated events.

Plasmacytoma at injection site

Plasmacytoma has been reported in proximity to the injection site after administration of Imlygic. The risks and benefits of Imlygic should be considered in patients with multiple myeloma or in whom plasmacytoma develops during treatment.

Obstructive airway disorder

Obstructive airway disorder has been reported following Imlygic treatment. Caution should be used when injecting lesions close to major airways.

HSV-1 seronegative patients

Patients who were HSV-1 seronegative at baseline were reported to have a greater incidence of pyrexia, chills, and influenza-like illness compared with those who were HSV-1 seropositive at baseline, especially within the period of the first 6 treatments (see section 4.8).

All patients

This medicinal product contains 20 mg sorbitol per 1 mL vial. The additive effect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account.

This medicinal product contains 7.7 mg sodium per 1 mL vial, equivalent to 0.4% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Effects on Driving

4.7    Effects on ability to drive and use machines

Talimogene laherparepvec may have a minor influence on the ability to drive and use machines.
Because of potential adverse reactions such as dizziness and confusional state (see section 4.8), patients should be advised to use caution when driving or operating machinery until they are certain that talimogene laherparepvec does not adversely affect them.