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  • CLASSES

    Other Antineoplastic Agents

    DEA CLASS

    Rx

    DESCRIPTION

    A live, attenuated HSV-1 that has been genetically modified to express human GM-CSF, indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery
    Most common adverse drug reactions are fatigue, chills, pyrexia, nausea, influenza-like illness, and injection site pain
    Contraindicated in pregnant women and immunocompromised patients

    COMMON BRAND NAMES

    Imlygic

    HOW SUPPLIED

    Imlygic Intralesional Inj Susp: 1mL, 1000000pfu, 100000000pfu

    DOSAGE & INDICATIONS

    For the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with malignant melanoma that is recurrent after initial surgery, or for lesions that appear after a complete response to previous treatment with talimogene laherparepvec.
    Intralesional dosage
    Adults, lesions larger than 5 cm (longest dimension)

    Up to 4 mL at a concentration of 106 (1 million) PFU/mL by intralesional injection for the initial injection into a cutaneous, subcutaneous, and/or nodal lesion that is larger than 5 cm at the longest dimension and visible, palpable, or detectable by ultrasound guidance (maximum volume per treatment visit, 4 mL for all lesions combined), followed after 3 weeks by 4 mL at a concentration of 108 (100 million) PFU/mL into any new lesion or remaining lesion larger than 5 cm (maximum volume per treatment visit, 4 mL for all lesions combined), every 2 weeks. If lesions are clustered together, inject them as a single lesion. Continue treatment for at least 6 months, unless other treatment is required or until there are no injectable lesions to treat. It may not be possible to inject all lesions at each treatment visit or over the full course of treatment; previously injected and/or uninjected lesions may be injected at subsequent treatment visits. If the lesion size changes between treatments, adjust the dose to the appropriate volume for the new lesion size. For the first treatment, inject the largest lesion first, prioritizing the remaining lesions based on size until all injectable lesions have been treated or the maximum injection volume of 4 mL has been reached. For subsequent treatments, inject any new lesions first, prioritizing the remaining lesions based on size until all injectable lesions have been treated or the maximum injection volume of 4 mL has been reached. CLINICAL TRIAL RESULTS: In a multicenter, randomized, open-label clinical trial, patients with unresectable stage IIIB, IIIC, and IV melanoma were treated with talimogene laherparepvec (n = 295) or subcutaneously administered GM-CSF (125 mcg/m2 daily for 14 days, every 28 days; n = 141). Patients treated with talimogene laherparepvec had a durable response rate (complete response or partial response, maintained for at least 6 months) of 16.3% compared with 2.1% of those who received GM-CSF (relative risk, 7.6%; p < 0.0001); the median time to response was 4.1 months (range, 1.2 to 16.7 months) in patients who received talimogene laherparepvec. The median overall survival was 22.9 months in the talimogene laherparepvec arm compared with 19 months in the GM-CSF arm (p = 0.116). Talimogene laherparepvec has not been shown to have an effect on visceral metastases.

    Adults, lesions 2.51 cm to 5 cm (longest dimension)

    Up to 2 mL at a concentration of 106 (1 million) PFU/mL by intralesional injection for the initial injection into each cutaneous, subcutaneous, and/or nodal lesion that is 2.51 cm to 5 cm at the longest dimension and visible, palpable, or detectable by ultrasound guidance (maximum volume per treatment visit, 4 mL for all lesions combined), followed after 3 weeks by 2 mL at a concentration of 108 (100 million) PFU/mL into each lesion (maximum volume per treatment visit, 4 mL for all lesions combined) every 2 weeks. If lesions are clustered together, inject them as a single lesion. Continue treatment for at least 6 months, unless other treatment is required or until there are no injectable lesions to treat. It may not be possible to inject all lesions at each treatment visit or over the full course of treatment; previously injected and/or uninjected lesions may be injected at subsequent treatment visits. If the lesion size changes between treatments, adjust the dose to the appropriate volume for the new lesion size. For the first treatment, inject the largest lesion first, prioritizing the remaining lesions based on size until all injectable lesions have been treated or the maximum injection volume of 4 mL has been reached. For subsequent treatments, inject any new lesions first, prioritizing the remaining lesions based on size until all injectable lesions have been treated or the maximum injection volume of 4 mL has been reached. CLINICAL TRIAL RESULTS: In a multicenter, randomized, open-label clinical trial, patients with unresectable stage IIIB, IIIC, and IV melanoma were treated with talimogene laherparepvec (n = 295) or subcutaneously administered GM-CSF (125 mcg/m2 daily for 14 days, every 28 days; n = 141). Patients treated with talimogene laherparepvec had a durable response rate (complete response or partial response, maintained for at least 6 months) of 16.3% compared with 2.1% of those who received GM-CSF (relative risk, 7.6%; p < 0.0001); the median time to response was 4.1 months (range, 1.2 to 16.7 months) in patients who received talimogene laherparepvec. The median overall survival was 22.9 months in the talimogene laherparepvec arm compared with 19 months in the GM-CSF arm (p = 0.116). Talimogene laherparepvec has not been shown to have an effect on visceral metastases.

    Adults, lesions 1.51 cm to 2.5 cm (longest dimension)

    Up to 1 mL at a concentration of 106 (1 million) PFU/mL by intralesional injection for the initial injection into each cutaneous, subcutaneous, and/or nodal lesion that is 1.51 cm to 2.5 cm at the longest dimension and visible, palpable, or detectable by ultrasound guidance (maximum volume per treatment visit, 4 mL for all lesions combined), followed after 3 weeks by 1 mL at a concentration of 108 (100 million) PFU/mL (maximum volume per treatment visit, 4 mL for all lesions combined) every 2 weeks. If lesions are clustered together, inject them as a single lesion. Continue treatment for at least 6 months, unless other treatment is required or until there are no injectable lesions to treat. It may not be possible to inject all lesions at each treatment visit or over the full course of treatment; previously injected and/or uninjected lesions may be injected at subsequent treatment visits. If the lesion size changes between treatments, adjust the dose to the appropriate volume for the new lesion size. For the first treatment, inject the largest lesion first, prioritizing the remaining lesions based on size until all injectable lesions have been treated or the maximum injection volume of 4 mL has been reached. For subsequent treatments, inject any new lesions first, prioritizing the remaining lesions based on size until all injectable lesions have been treated or the maximum injection volume of 4 mL has been reached. CLINICAL TRIAL RESULTS: In a multicenter, randomized, open-label clinical trial, patients with unresectable stage IIIB, IIIC, and IV melanoma were treated with talimogene laherparepvec (n = 295) or subcutaneously administered GM-CSF (125 mcg/m2 daily for 14 days, every 28 days; n = 141). Patients treated with talimogene laherparepvec had a durable response rate (complete response or partial response, maintained for at least 6 months) of 16.3% compared with 2.1% of those who received GM-CSF (relative risk, 7.6%; p < 0.0001); the median time to response was 4.1 months (range, 1.2 to 16.7 months) in patients who received talimogene laherparepvec. The median overall survival was 22.9 months in the talimogene laherparepvec arm compared with 19 months in the GM-CSF arm (p = 0.116). Talimogene laherparepvec has not been shown to have an effect on visceral metastases.

    Adults, lesions 0.51 cm to 1.5 cm (longest dimension)

    Up to 0.5 mL at a concentration of 106 (1 million) PFU/mL by intralesional injection for the initial injection into each cutaneous, subcutaneous, and/or nodal lesion that is 0.51 cm to 1.5 cm at the longest dimension and visible, palpable, or detectable by ultrasound guidance (maximum volume per treatment visit, 4 mL for all lesions combined), followed after 3 weeks by 0.5 mL at a concentration of 108 (100 million) PFU/mL (maximum volume per treatment visit, 4 mL for all lesions combined) every 2 weeks. If lesions are clustered together, inject them as a single lesion. Continue treatment for at least 6 months, unless other treatment is required or until there are no injectable lesions to treat. It may not be possible to inject all lesions at each treatment visit or over the full course of treatment; previously injected and/or uninjected lesions may be injected at subsequent treatment visits. If the lesion size changes between treatments, adjust the dose to the appropriate volume for the new lesion size. For the first treatment, inject the largest lesion first, prioritizing the remaining lesions based on size until all injectable lesions have been treated or the maximum injection volume of 4 mL has been reached. For subsequent treatments, inject any new lesions first, prioritizing the remaining lesions based on size until all injectable lesions have been treated or the maximum injection volume of 4 mL has been reached. CLINICAL TRIAL RESULTS: In a multicenter, randomized, open-label clinical trial, patients with unresectable stage IIIB, IIIC, and IV melanoma were treated with talimogene laherparepvec (n = 295) or subcutaneously administered GM-CSF (125 mcg/m2 daily for 14 days, every 28 days; n = 141). Patients treated with talimogene laherparepvec had a durable response rate (complete response or partial response, maintained for at least 6 months) of 16.3% compared with 2.1% of those who received GM-CSF (relative risk, 7.6%; p < 0.0001); the median time to response was 4.1 months (range, 1.2 to 16.7 months) in patients who received talimogene laherparepvec. The median overall survival was 22.9 months in the talimogene laherparepvec arm compared with 19 months in the GM-CSF arm (p = 0.116). Talimogene laherparepvec has not been shown to have an effect on visceral metastases.

    Adults, lesions 0.5 cm or smaller (longest dimension)

    Up to 0.1 mL at a concentration of 106 (1 million) PFU/mL by intralesional injection for the initial injection into each cutaneous, subcutaneous, and/or nodal lesion that is 0.5 cm or smaller at the longest dimension and visible, palpable, or detectable by ultrasound guidance (maximum volume per treatment visit, 4 mL for all lesions combined), followed after 3 weeks by 0.1 mL at a concentration of 108 (100 million) PFU/mL (maximum volume per treatment visit, 4 mL for all lesions combined) every 2 weeks. If lesions are clustered together, inject them as a single lesion. Continue treatment for at least 6 months, unless other treatment is required or until there are no injectable lesions to treat. It may not be possible to inject all lesions at each treatment visit or over the full course of treatment; previously injected and/or uninjected lesions may be injected at subsequent treatment visits. If the lesion size changes between treatments, adjust the dose to the appropriate volume for the new lesion size. For the first treatment, inject the largest lesion first, prioritizing the remaining lesions based on size until all injectable lesions have been treated or the maximum injection volume of 4 mL has been reached. For subsequent treatments, inject any new lesions first, prioritizing the remaining lesions based on size until all injectable lesions have been treated or the maximum injection volume of 4 mL has been reached. CLINICAL TRIAL RESULTS: In a multicenter, randomized, open-label clinical trial, patients with unresectable stage IIIB, IIIC, and IV melanoma were treated with talimogene laherparepvec (n = 295) or subcutaneously administered GM-CSF (125 mcg/m2 daily for 14 days, every 28 days; n = 141). Patients treated with talimogene laherparepvec had a durable response rate (complete response or partial response, maintained for at least 6 months) of 16.3% compared with 2.1% of those who received GM-CSF (relative risk, 7.6%; p < 0.0001); the median time to response was 4.1 months (range, 1.2 to 16.7 months) in patients who received talimogene laherparepvec. The median overall survival was 22.9 months in the talimogene laherparepvec arm compared with 19 months in the GM-CSF arm (p = 0.116). Talimogene laherparepvec has not been shown to have an effect on visceral metastases.

    MAXIMUM DOSAGE

    Adults

    4 mL per treatment visit (all lesions combined).

    Geriatric

    4 mL per treatment visit (all lesions combined).

    Adolescents

    Safety and efficacy have not been established in pediatric patients.

    Children

    Safety and efficacy have not been established in pediatric patients.

    Infants

    Safety and efficacy have not been established in pediatric patients.

    Neonates

    Neonates should not be exposed to talimogene laherparepvec due to the risk of transmission of HSV-1. Neonates should avoid direct contact with injected lesions, dressings, or body fluids of treated patients.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available as clinical studies have not been conducted; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available as clinical studies have not been conducted; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    CAUTION: Observe and exercise universal precautions for handling, preparing, administering, and disposing of biohazardous drugs.
    Healthcare providers who are immunocompromised or pregnant should not prepare or administer talimogene laherparepvec, and should not come into direct contact with the injection sites, dressings, or body fluids of treated patients.
    Cover any exposed wounds prior to handling talimogene laherparepvec.
    For spills or surfaces that have come into contact with talimogene laherparepvec, clean the area using a virucidal agent such as 1% sodium hypochlorite or 70% isopropyl alcohol; blot using an absorbent material.
    Patients should place used dressings and cleaning materials into a sealed plastic bag and dispose in household waste.

    Injectable Administration
    Intravenous Administration

    For intralesional injection only. Do not administer intravenously.

    Other Injectable Administration

    Intralesional Injection
    Preparation:
    Determine the total volume needed, up to 4 mL.
    Keeping the vial in the original carton, thaw frozen talimogene laherparepvec vials at room temperature (22 to 25 degrees Celsius, or 68 to 77 degrees Farenheit) for approximately 30 minutes, until talimogene laherparepvec is liquid. Do not expose the vial to higher temperatures.
    Swirl gently; do not shake.
    Storage after thawing: Refrigerate thawed talimogene laherparepvec (2 to 8 degrees Celsius, or 36 to 46 degrees Farenheit) in the original vial and carton for up to 12 hours (106 (1 million) PFU/mL) or 48 hours (108 (100 million) PFU/mL), depending on the vial strength. Protect from light. Do not refreeze.
    When ready for administration, prepare the syringes and needles. Small unit syringes (e.g., 0.5 mL insulin syringes) are recommended for better injection control; a detachable needle of 18 to 26 gauge may be used for withdrawal from the vial, and 22 to 26 gauge for injection.
    Administration:
    Administer talimogene laherparepvec immediately after preparing syringes.
    Clean the lesion and surrounding areas with alcohol; treat the periphery of the lesion with a topical or local anesthetic agent if necessary. Do not inject anesthetic agent directly into the lesion.
    Using a single insertion point, inject talimogene laherparepvec along multiple tracks as far as the radial reach of the needle allows within the lesion, to achieve even and complete dispersion; if necessary, pull the needle back without exiting the lesion to allow for redirection as many times as necessary until the full dose is evenly and completely dispersed. Multiple insertion sites may be used if a lesion is larger than the radial reach of the needle.
    When removing the needle, withdraw it from the lesion slowly to avoid leakage from the insertion point.
    Repeat these steps for all lesions to be injected. Use a new needle any time the needle is completely removed from a lesion and each time a different lesion is injected.
    After injection, apply pressure to the injection site with sterile guaze for at least 30 seconds.
    Swab the injection sites and surrounding areas with alcohol.
    Change gloves and cover the injected lesions with an absorbent pad and dry occlusive dressing.
    Wipe the exterior of the occlusive dressing with alcohol.
    Patients should keep the injection site covered for at least the first week after each treatment, or longer if the injection site is still weeping or oozing. Replace the dressing if it falls off.

    STORAGE

    Imlygic:
    - Do not refreeze
    - Protect from light
    - Store and transport product at -130 to -94 degrees F.
    - Store in carton until time of use

    CONTRAINDICATIONS / PRECAUTIONS

    Acquired immunodeficiency syndrome (AIDS), bone marrow suppression, chemotherapy, corticosteroid therapy, diabetes mellitus, geriatric, herpes infection, herpes simplex keratitis (dendritic keratitis), human immunodeficiency virus (HIV) infection, hypogammaglobulinemia, immunosuppression, leukemia, lymphoma, organ transplant, radiation therapy, renal failure

    The use of talimogene laherparepvec, a live, attenuated herpes simplex virus, is contraindicated in patients who are immunosuppressed, as immunosuppression may cause life-threatening disseminated herpetic infection in these patients. In clinical studies, herpes infections (including cold sores and herpes simplex keratitis (dendritic keratitis) have been reported with talimogene laherparepvec treatment; talimogene laherparepvec DNA was found in injected tumor of mice through 84 days and in blood samples through 14 days after the last administration. Suspected herpetic lesions should be reported to Amgen at 1-855-465-9442; patients or close contacts should contact their healthcare provider for evaluation and follow standard hygienic practices to prevent viral transmission. Immunocompromised patients include those with a history of primary or acquired immunodeficient states, leukemia, lymphoma, acquired immunodeficiency syndrome (AIDS), or other clinical manifestations of infection with human immunodeficiency virus (HIV) infection, and those on immunosuppressive therapy including patients who may have received an organ transplant. Additionally, geriatric patients; patients with diabetes mellitus, renal failure, hypogammaglobulinemia or bone marrow suppression; and patients who are receiving radiation therapy, chemotherapy, or chronic corticosteroid therapy may be immunosuppressed.

    Peripheral vascular disease

    Patients with peripheral vascular disease or previous radiation therapy may be at increased risk of impaired healing at the injection site. Careful wound care and infection precautions are recommended, as necrosis or ulceration of tumor tissue have been reported. If there is persistent infection or delayed healing at the injection site, consider the risks and benefits of therapy before continuing treatment with talimogene laherparepvec.

    Accidental exposure, ocular exposure

    Accidental exposure to talimogene laherparepvec may lead to herpetic infection. Accidental needle stick and splashback to the eyes resulting in ocular exposure have been reported in healthcare providers during preparation and administration. If an accidental exposure occurs, clean the affected area thoroughly with soap and water and/or a disinfectant; if mucous membranes or eyes are involved, flush with clean water for at least 15 minutes. Caregivers should wear protective gloves when applying or changing occlusive dressings; used dressings and cleaning materials should be placed into a sealed plastic bag and disposed of in household waste. If signs or symptoms of herpetic infection develop, the exposed person should contact their healthcare provider. Healthcare providers, close contacts (household members, caregivers, sex partners, or persons sharing the same bed), pregnant women, and newborns should avoid direct contact with injected lesions, dressings, or body fluids of treated patients. Caregivers should wear protective gloves when applying or changing occlusive dressings; used dressings and cleaning materials should be placed into a sealed plastic bag and disposed of in household waste. Patients should avoid touching or scratching sites or dressings, as this could inadvertently transfer talimogene laherparepvec to other areas of the body.

    Autoimmune disease

    Immune-mediated events, including glomerulonephritis, vasculitis, pneumonitis, worsening psoriasis, and vitiligo have been reported in patients treated with talimogene laherparepvec in clinical trials. Consider the risks and benefits of talimogene laherparepvec therapy in patients who have underlying autoimmune disease or before continuing treatment in patients who develop immune-mediated events.

    Multiple myeloma

    Plasmacytoma has been reported in proximity to the injection site after administration of talimogene laherparepvec to a patient with smoldering multiple myeloma; consider the risks and benefits of talimogene laherparepvec in patients with multiple myeloma or in whom plasmacytoma develops during treatment.

    Pregnancy

    Talimogene laherparepvec is contraindicated for receipt during pregnancy; additionally, pregnant women not receiving treatment should avoid direct contact with injected lesions, dressings, or body fluids of treated patients. Healthcare providers who are pregnant should not administer talimogene laherparepvec. If a patient becomes pregnant during treatment, they should be apprised of the potential hazards to the fetus and neonate. If a pregnant woman has an infection with wild-type herpes simplex virus Type 1 (HSV-1), either 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. HSV-1 infections have been associated with serious adverse effects, including multi-organ failure and death, if a fetus or neonate contracts the wild-type herpes infection. While there are no adequate and well-controlled studies conducted in pregnant women, there could be a risk to the fetus or neonate if talimogene laherparepvec acts in the same manner. No effects on embryo-fetal development have been observed in pregnant mice. However, the design of the study limits its application to humans, including administration of talimogene laherparepvec expressing human GM-CSF, which is not biologically active in mice; unknown transplacental kinetics of talimogene laherparepvec in mice; and unknown significance of talimogene laherparepvec dose extrapolation from animal to human based on body weight.

    Contraception requirements, reproductive risk

    Counsel patients about the reproductive risk and contraception requirements during treatment with talimogene laherparepvec. Because of the risk of transmission of HSV-1 to the fetus or neonate, females should avoid pregnancy and use effective contraception during treatment with talimogene laherparepvec. Additionally, sex partners of treated patients should avoid direct contact with injected lesions, dressings, or body fluids of treated patients. It is prudent that females of reproductive potential undergo pregnancy testing prior to initiation of therapy. Women who become pregnant while receiving talimogene laherparepvec should be apprised of the potential hazard to the fetus.

    Breast-feeding

    It is not known whether talimogene laherparepvec is present in human milk. Many drugs are excreted in human milk including antibodies. Due to the potential for serious adverse reactions in nursing infants from talimogene laherparepvec, advise women to discontinue breast-feeding during treatment.

    Pulmonary toxicity

    Pulmonary toxicity (i.e., obstructive airway disorder) has been reported with talimogene laherparepvec use. Use caution when administering talimogene laherparepvec close to major airways.

    ADVERSE REACTIONS

    Severe

    vomiting / Early / 1.7-1.7
    influenza / Delayed / 0-1.0
    injection site reaction / Rapid / 0-1.0
    weight loss / Delayed / 0-1.0
    abdominal pain / Early / 0-1.0
    nausea / Early / 0-1.0
    diarrhea / Early / 0-1.0
    myalgia / Early / 0-1.0
    arthralgia / Delayed / 0-1.0
    headache / Early / 0-1.0
    keratitis / Delayed / Incidence not known
    glomerulonephritis / Delayed / Incidence not known
    vasculitis / Delayed / Incidence not known
    tissue necrosis / Early / Incidence not known
    pulmonary toxicity / Early / Incidence not known
    thrombosis / Delayed / Incidence not known

    Moderate

    constipation / Delayed / 11.6-11.6
    psoriasis / Delayed / Incidence not known
    pneumonitis / Delayed / Incidence not known
    skin ulcer / Delayed / Incidence not known
    impaired wound healing / Delayed / Incidence not known
    atopic dermatitis / Delayed / Incidence not known

    Mild

    chills / Rapid / 48.6-48.6
    fever / Early / 42.8-42.8
    dizziness / Early / 9.6-9.6
    infection / Delayed / Incidence not known
    skin discoloration / Delayed / Incidence not known
    rash (unspecified) / Early / Incidence not known

    DRUG INTERACTIONS

    Acyclovir: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
    Amantadine: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
    Antivirals: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
    Atazanavir; Cobicistat: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
    Cidofovir: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
    Cobicistat: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
    Darunavir; Cobicistat: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
    Famciclovir: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
    Foscarnet: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
    Ganciclovir: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
    Interferon Alfa-2b; Ribavirin: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
    Ribavirin: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
    Rimantadine: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
    Valacyclovir: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
    Valganciclovir: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.

    PREGNANCY AND LACTATION

    Pregnancy

    Talimogene laherparepvec is contraindicated for receipt during pregnancy; additionally, pregnant women not receiving treatment should avoid direct contact with injected lesions, dressings, or body fluids of treated patients. Healthcare providers who are pregnant should not administer talimogene laherparepvec. If a patient becomes pregnant during treatment, they should be apprised of the potential hazards to the fetus and neonate. If a pregnant woman has an infection with wild-type herpes simplex virus Type 1 (HSV-1), either 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. HSV-1 infections have been associated with serious adverse effects, including multi-organ failure and death, if a fetus or neonate contracts the wild-type herpes infection. While there are no adequate and well-controlled studies conducted in pregnant women, there could be a risk to the fetus or neonate if talimogene laherparepvec acts in the same manner. No effects on embryo-fetal development have been observed in pregnant mice. However, the design of the study limits its application to humans, including administration of talimogene laherparepvec expressing human GM-CSF, which is not biologically active in mice; unknown transplacental kinetics of talimogene laherparepvec in mice; and unknown significance of talimogene laherparepvec dose extrapolation from animal to human based on body weight.

    It is not known whether talimogene laherparepvec is present in human milk. Many drugs are excreted in human milk including antibodies. Due to the potential for serious adverse reactions in nursing infants from talimogene laherparepvec, advise women to discontinue breast-feeding during treatment.

    MECHANISM OF ACTION

    Talimogene laherparepvec is a live, attenuated HSV-1 that has been genetically modified to replicate within tumors and express the immune stimulatory protein, GM-CSF. Administration of a talimogene laherparepvec causes lysis of tumors, followed by release of tumor-derived antigens, which together with virally derived GM-CSF may promote an antitumor immune response. The exact mechanism of action is unknown.

    PHARMACOKINETICS

    Talimogene laherparepvec is administered by intralesional injection; do not administer talimogene laherparepvec intravenously. Following repeat administration in mice, talimogene laherparepvec DNA was primarily detected in the tumor (highest levels), blood, spleen, lymph node, liver, heart and kidney; it was not detected in bone marrow, eyes, lachrymal glands, nasal mucosa, or feces. The DNA of talimogene laherparepvec was found in the injected tumor through 84 days and in blood samples through 14 days after the last dose. In melanoma patients who received intralesional talimogene laherparepvec at a dose and schedule similar to the clinical study (n = 20), talimogene laherparepvec DNA was present in the blood in 85% of patients, and in the urine of 20% of patients during the study; peak urine levels were detected on the day of treatment. Infectious talimogene laherparepvec virus was detected at the injection site of 3 patients (15%) at a single time point each, all within the first week after the initial injection. Additionally, the exterior of the occlusive dressings was positive for talimogene laherparepvec DNA, but not for infectious virus, in 70% of patients during the study. The number of patients with measurable DNA on the exterior of the occlusive dressings declined over time with no measurable DNA by the third treatment in 13 patients.