Talimogene laherparepvec interacts in the following cases:
Acyclovir and other anti-viral agents may interfere with the effectiveness of Imlygic if administered systemically or topically directly to the injection site. Consider the risks and benefits of Imlygic treatment before administering acyclovir or other anti-viral agents indicated for management of herpetic infection.
Necrosis or ulceration of tumour tissue may occur following talimogene laherparepvec 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.
In clinical studies, impaired healing at the injection site has been reported. Talimogene laherparepvec 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 vascularised areas).
The risks and benefits of talimogene laherparepvec should be considered before continuing treatment if persistent infection or delayed healing develops.
In clinical studies, immune-mediated events including as glomerulonephritis, vasculitis, pneumonitis, worsening psoriasis, and vitiligo have been reported in patients treated with talimogene laherparepvec.
The risks and benefits of talimogene laherparepvec 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 has been reported in proximity to the injection site after administration of talimogene laherparepvec. The risks and benefits of talimogene laherparepvec should be considered in patients with multiple myeloma or in whom plasmacytoma develops during treatment.
In clinical studies, herpetic infections (including cold sores and herpes keratitis) have been reported in patients treated with talimogene laherparepvec. Symptoms of a local or systemic infection possibly related to talimogene laherparepvec 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 talimogene laherparepvec 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 talimogene laherparepvec 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 talimogene laherparepvec if administered systemically or topically directly to the injection site.
Adequate and well controlled studies with talimogene laherparepvec have not been conducted in pregnant women.
If a pregnant woman has an infection with wild type HSV-1 (primary or reactivation), there is potential for the virus to cross the placental barrier, and also a risk of transmission during birth due to viral shedding. Infections with wild-type HSV-1 have been associated with serious adverse effects, including multi-organ failure and death, if a foetus or neonate contracts the wild type herpes infection.
While there are no clinical data to date on talimogene laherparepvec infections in pregnant women, there could be a risk to the foetus or neonate if talimogene laherparepvec were to act in the same manner. No effects on embryo-foetal development have been observed in animal studies. As a precautionary measure, it is preferable to avoid the use of talimogene laherparepvec during pregnancy.
Transplacental metastases of malignant melanoma can occur. Because talimogene laherparepvec is designed to enter and replicate in the tumour tissue, there could be a risk of foetal exposure to talimogene laherparepvec from tumour tissue that has crossed the placenta.
If talimogene laherparepvec is used during pregnancy, or if the patient becomes pregnant while taking talimogene laherparepvec, the patient should be apprised of the potential hazards to the foetus and/or neonate.
It is unknown whether talimogene laherparepvec is transferred into human milk. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from talimogene laherparepvec therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Women of childbearing potential should be advised to use an effective method of contraception to prevent pregnancy during treatment with talimogene laherparepvec.
All patients should be advised to use a latex condom during sexual contact to prevent possible transmission of talimogene laherparepvec.
No clinical studies have been performed to evaluate the effects of talimogene laherparepvec on fertility.
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, patients should be advised to use caution when driving or operating machinery until they are certain that talimogene laherparepvec does not adversely affect them.
The safety of talimogene laherparepvec was evaluated in the pivotal study where 292 patients received at least 1 dose of talimogene laherparepvec. The median duration of exposure to talimogene laherparepvec was 23 weeks (5.3 months). Twenty six (26) patients were exposed to talimogene laherparepvec for at least one year.
The most commonly reported adverse reactions (≥25%) in talimogene laherparepvec-treated patients were fatigue (50.3%), chills (48.6%), pyrexia (42.8%), nausea (35.6%), influenza-like illness (30.5%), and injection site pain (27.7%). Overall, ninety eight per cent (98%) of these adverse reactions reported were mild or moderate in severity. The most common grade 3 or higher adverse reaction was cellulitis (2.1%).
Adverse reactions were determined based on clinical trials in patients with melanoma treated with talimogene laherparepvec compared to GM-CSF and post-marketing experience. Incidence of adverse reactions are presented by system organ class and by frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10) and uncommon (≥1/1,000 to <1/100). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Adverse reactions from clinical trials in patients with melanoma and post-marketing experience:
Common: Cellulitis*, Oral herpes
Uncommon: Incision site infection
Common: Tumour pain, Infected neoplasm
Uncommon: Plasmacytoma at injection site*
Very common: Oedema peripheral
Common: Anaemia
Common: Immune-mediated events†*
Uncommon: Hypersensitivity
Common: Dehydration
Very common: Headache
Common: Confusional state, Anxiety, Depression, Dizziness, Insomnia
Uncommon: Keratitis herpetic
Common: Ear pain
Common: Tachycardia
Common: Deep vein thrombosis, Hypertension, Flushing
Very common: Cough
Common: Dyspnoea, Oropharyngeal pain, Upper respiratory tract infection
Uncommon: Obstructive airways disorder
Very common: Vomiting, Diarrhoea, Constipation, Nausea
Common: Abdominal pain, Abdominal discomfort
Common: Vitiligo, Rash, Dermatitis
Uncommon: Granulomatous dermatitis
Very common: Myalgia, Arthralgia, Pain in extremity
Common: Back pain, Groin pain
Very common: Influenza like illness*, Pyrexia, Chills, Fatigue, Pain, Injection site reactions§
Common: Malaise, Axillary pain
Common: Weight decreased
Common: Wound complication, Wound secretion, Contusion, Procedural pain
§ Injection site reactions include: very common term of injection site pain, common terms of injection site erythema, injection site haemorrhage, injection site swelling, injection site reaction, injection site inflammation, secretion discharge, injection site discharge, uncommon term of injection site warmth.
† Immune mediated events include: uncommon terms of vasculitis, pneumonitis, worsening psoriasis and glomerulonephritis.
* See description of selected adverse reactions
Immune-mediated events reported in the pivotal clinical study included a case of worsening psoriasis in a patient with a prior history of psoriasis, one case of pneumonitis in a patient with a prior history of autoimmune disease, one case of vasculitis, and two cases of glomerulonephritis of which one presented with acute renal failure.
In clinical trials, one case of plasmacytoma at injection site was observed in a patient who was found to have multiple myeloma.
In the pivotal clinical trial (study 005/05), events of cellulitis were recorded, some of them being considered as serious adverse events. However, none lead to permanent discontinuation of talimogene laherparepvec treatment. Careful wound care and infection precautions are recommended, particularly if tissue necrosis results in open wounds.
90% of patients treated with talimogene laherparepvec experienced influenza-like symptoms. Pyrexia, chills, and influenza like illness, which can occur any time during talimogene laherparepvec treatment, generally resolved within 72 hours. These events were reported more frequently within the period of the first 6 treatments, particularly in patients who were HSV-1 negative at baseline.
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