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Talimogene laherparepvec: Drug information

Talimogene laherparepvec: Drug information
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For additional information see "Talimogene laherparepvec: Patient drug information"

For abbreviations, symbols, and age group definitions show table
Brand Names: US
  • Imlygic
Pharmacologic Category
  • Antineoplastic Agent, Oncolytic Virus
Dosing: Adult

Note: Health care providers who are immunocompromised or pregnant should not prepare or administer talimogene laherparepvec and should not have direct contact with injection sites, dressings, or body fluids of patients treated with talimogene laherparepvec. Personal protective equipment (eg, gown or laboratory coat, safety glasses or face shield, gloves) should be worn during preparation and administration. Refer to "Preparation for Administration" and "Administration" for further information.

Administer by intralesional injection into cutaneous, SUBQ, and/or nodal lesions that are visible, palpable, or detectable by ultrasound. 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 lesion(s) may be treated at subsequent visits.

Melanoma, unresectable

Melanoma, unresectable: Intralesional: Maximum volume (per treatment visit, for all injected lesions combined): 4 mL. Continue treatment for at least 6 months unless other therapy is necessary or until there are no injectable lesions to treat. Reinitiate treatment if new unresectable lesions appear after a previous complete response.

Use the following to determine the volume of talimogene laherparepvec to be injected (lesion size is based on longest dimension; when lesions are clustered together, inject them as a single lesion): Intralesional:

• If the lesion size is >5 cm, inject up to 4 mL

• If the lesion size is >2.5 cm to 5 cm, inject up to 2 mL

• If the lesion size is >1.5 cm to 2.5 cm, inject up to 1 mL

• If the lesion size is >0.5 cm to 1.5 cm, inject up to 0.5 mL

• If the lesion size is ≤0.5 cm, inject up to 0.1 mL

Initial treatment visit: Intralesional: Inject up to 4 mL at a concentration of 106 (1 million) PFU/mL. Inject largest lesion(s) first; inject remaining lesion(s) based on lesion size until maximum injection volume is reached or all lesions have been treated.

Second treatment visit (3 weeks after initial treatment): Intralesional: Inject up to 4 mL at a concentration of 108 (100 million) PFU/mL. Inject any new lesion(s) that have developed since initial treatment first; inject remaining lesion(s) based on lesion size until maximum injection volume is reached or all lesions have been treated.

All subsequent treatment visits, including reinitiation (2 weeks after previous treatment): Intralesional: Inject up to 4 mL at a concentration of 108 (100 million) PFU/mL. Inject any new lesion(s) that have developed since previous treatment first; inject remaining lesion(s) based on lesion size until maximum injection volume is reached or all lesions have been treated.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Adjustment for Toxicity: Adult

Consider risk:benefit ratio of talimogene laherparepvec treatment in patients with underlying autoimmune disease or prior to continuing talimogene laherparepvec treatment in patients who develop immune-mediated events, patients with persistent infection or impaired/delayed wound healing at injection site(s), or patients with multiple myeloma or in those who develop plasmacytoma during treatment.

If herpes-like lesions develop, follow standard practice to prevent viral transmission; contact a health care provider for evaluation.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported with adults.

>10%:

Gastrointestinal: Constipation (12%), diarrhea (19%), nausea (36%), vomiting (21%)

Local: Pain at injection site (28%)

Nervous system: Chills (49%), fatigue (50%), headache (19%)

Neuromuscular & skeletal: Arthralgia (17%), limb pain (16%), myalgia (18%)

Respiratory: Flu-like symptoms (31%)

Miscellaneous: Fever (43%)

1% to 10%:

Endocrine & metabolic: Weight loss (6%)

Gastrointestinal: Abdominal pain (9%)

Nervous system: Dizziness (10%)

Respiratory: Oropharyngeal pain (6%)

Frequency not defined:

Cardiovascular: Deep vein thrombosis, vasculitis

Dermatologic: Cellulitis, dermatitis, exacerbation of psoriasis, skin rash, vitiligo

Gastrointestinal: Oral herpes simplex infection

Ophthalmic: Herpes simplex keratitis

Renal: Glomerulonephritis

Respiratory: Pneumonitis

Postmarketing:

Infection: Bacterial infection (systemic), herpes virus infection (can be disseminated)

Respiratory: Obstructive pulmonary disease

Contraindications

Immunocompromised patients, including those with a history of primary or acquired immunodeficient states, leukemia, lymphoma, AIDS or other clinical manifestations of infection with human immunodeficiency viruses, and those on immunosuppressive therapy; pregnancy.

Warnings/Precautions

Concerns related to adverse effects:

• Hepatic hemorrhage: Cases of hepatic hemorrhage resulting in hospitalization and death have been reported when talimogene laherparepvec was administered as a transcutaneous intrahepatic injection (not an approved route of administration).

• Immune-mediated events: Immune-mediated events (eg, glomerulonephritis, pneumonitis, vasculitis, vitiligo, and worsening psoriasis) have been reported in clinical studies. Consider risk/benefit ratio of initiating treatment in patients with underlying autoimmune disease or prior to continuing talimogene laherparepvec treatment in patients who develop immune-mediated events.

• Infection: Herpetic infections (eg, cold sores and herpetic keratitis) have been reported; severe disseminated herpetic infection may occur in patients treated with talimogene laherparepvec, including life-threatening or fatal infections in immunocompromised patients. If herpes-like lesions develop, follow standard practice to prevent viral transmission; contact a health care provider for evaluation. Suspected herpetic lesions should be reported to Amgen at 1-855-465-9442. Accidental talimogene laherparepvec exposure may lead to herpetic infection; exposed individuals should contact a health care provider if signs/symptoms of herpetic infection develop.

• Injection-site complications: Injection-site complications, such as necrosis, tumor tissue ulceration, and impaired healing, may occur during treatment with talimogene laherparepvec. Cellulitis and systemic bacterial infection have been observed. Infection precautions are recommended for wounds, particularly if tissue necrosis results in open wounds. Patients with underlying risk factors for impaired wound healing (eg, previous radiation at the injection site or lesions in poorly vascularized areas) may be at risk for complications. One patient had a lower extremity amputation 6 months after talimogene laherparepvec administration due to an infected non-healing wound. Consider risk/benefit of continued treatment in patients with persistent infection or impaired wound healing at injection site(s).

• Pulmonary toxicity: Obstructive airway disorder has been observed following talimogene laherparepvec therapy; use caution when injecting lesions close to major airways.

Disease-related concerns:

• Multiple myeloma: In one clinical study, a patient with smoldering multiple myeloma developed a plasmacytoma near the talimogene laherparepvec injection site. Consider the risks/benefits of talimogene laherparepvec therapy in patients with multiple myeloma or in those who develop plasmacytoma during treatment.

Concurrent drug therapy issues:

• Acyclovir: Talimogene laherparepvec is sensitive to acyclovir. Acyclovir (or other antiviral medications) may interfere with the efficacy of talimogene laherparepvec; consider the risks and benefits of treatment prior to administering antiviral agents.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension, Intralesional [preservative free]:

Imlygic: 106 (1 million) PFU/mL (1 mL); 108 (100 million) PFU/mL (1 mL) [contains bovine serum]

Pricing: US

Suspension (Imlygic Intralesional)

1000000 units/mL (per mL): $79.85

100000000 units/mL (per mL): $7,983.76

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Adult

Intralesional injection:

Immunocompromised or pregnant health care providers should not prepare or administer talimogene laherparepvec and should not have direct contact with injection sites, dressings, or body fluids of patients treated with talimogene laherparepvec.

Avoid accidental exposure (may lead to herpetic infection); follow biohazard precautions (personal protective equipment) for administration. Health care providers, close contacts (eg, household members, caregivers, sex partners, or persons sharing the same bed), pregnant patients, and newborns should avoid direct contact with the injected lesion, dressings, and/or patient body fluids. Protective gloves should be worn when changing dressing. Safely dispose of used dressings, gloves, and cleaning materials; patients may place in a sealed plastic bag and dispose of in household waste. If accidental exposure occurs through an eye splash or a splash to mucous membranes, flush the area with clean water for at least 15 minutes. If exposure to broken skin or a needle stick occurs, clean the affected area thoroughly with soap and water and/or a disinfectant.

Administer by intralesional injection into cutaneous, subcutaneous, and/or nodal lesions that are visible, palpable, or detectable by ultrasound. Clean the lesion and surrounding areas with alcohol and allow to dry. If necessary, treat the injection site with a topical or local anesthetic agent (but do not inject the anesthetic directly into the lesion [inject around periphery of lesion]). Using a single insertion point, inject talimogene laherparepvec (using a detachable or nondetachable 22- to 26-gauge needle) along multiple tracks as far as the needle allows within the lesion to achieve dispersion; multiple insertion points may be used if a lesion is larger than the radial reach of the needle. Small unit syringes (eg, 0.5 mL insulin syringes) are recommended for better injection control.

Inject talimogene laherparepvec evenly and completely within the lesion by pulling the needle back without removing it from the lesion. Redirect the needle as necessary while injecting the remainder of the dose; continue until the full dose is evenly and completely dispersed. Remove the needle from the lesion slowly to avoid leakage. Repeat steps for other lesions to be treated. Use a new needle if the needle is completely removed from a lesion and each time a different lesion is injected. Apply pressure with sterile gauze for at least 30 seconds after the injection is completed; swab the injection site(s) and surrounding areas with alcohol. Change gloves, then cover lesion(s) with an absorbent pad and dry occlusive dressing, then wipe the exterior of the dressing with alcohol. The injection site should be covered for at least the first week after each treatment or longer if the injection site is weeping or oozing (replace dressing if it falls off).

Counsel patients to avoid touching or scratching injection site(s) or the dressings (may lead to inadvertent transfer of drug to other parts of the body).

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Imlygic: http://pi.amgen.com/united_states/imlygic/imlygic_mg.pdf

Use: Labeled Indications

Melanoma, unresectable: Treatment (local) of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery

Limitations of use: Talimogene laherparepvec has not been shown to improve overall survival or have an effect on visceral metastases.

Medication Safety Issues
High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs (chemotherapeutic agent, parenteral and oral; contraindicated in pregnancy) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

Other safety concerns:

Health care providers who are immunocompromised or pregnant should not prepare or administer talimogene laherparepvec and should not come into direct contact with injection sites, dressings, or body fluids of treated patients.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Antiherpetic Antivirals: May diminish the therapeutic effect of Talimogene Laherparepvec. Risk C: Monitor therapy

Corticosteroids (Systemic): May enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Immunosuppressants (Cytotoxic Chemotherapy): May enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Immunosuppressants (Miscellaneous Oncologic Agents): May enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Immunosuppressants (Therapeutic Immunosuppressant Agents): May enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Methotrexate: May enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Reproductive Considerations

Patients who could become pregnant should use effective contraception during talimogene laherparepvec therapy.

Pregnancy Considerations

Use is contraindicated in pregnancy.

Talimogene laherparepvec is a live, attenuated, genetically modified herpes simplex virus type 1 (HSV-1). HSV-1 is known to cross the placenta, can be transmitted during birth, and produce infections in the fetus or neonate. It is not known if this can occur following exposure to talimogene laherparepvec. Pregnant patients should not prepare or administer this medication. Pregnant patients who are in close contact of patients treated with talimogene laherparepvec should not change dressings or clean injection sites, and should avoid direct contact with the injection site, dressings, or body fluids of patients.

Breastfeeding Considerations

It is not known if talimogene laherparepvec is present in breast milk. The manufacturer recommends a decision be made to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother.

Monitoring Parameters

Monitor for signs/symptoms of herpetic infections (eg, cold sores and herpetic keratitis), injection-site complications, obstructive airway disease, and immune-mediated events. Monitor wound(s) carefully.

Mechanism of Action

Talimogene laherparepvec is a genetically modified attenuated herpes simplex virus 1 (HSV) oncolytic virus which selectively replicates in and lyses tumor cells (Andtbacka 2015). Talimogene laherparepvec is modified through deletion of two nonessential viral genes. Deletion of the herpes virus neurovirulence factor gene ICP34.5 diminishes viral pathogenicity and increases tumor-selective replication; deletion of the ICP47 gene reduces virally mediated suppression of antigen presentation and increases the expression of the HSV US11 gene (Andtbacka 2015). Virally derived GM-CSF recruits and activates antigen-presenting cells, leading to an antitumor immune response.

Pharmacokinetics (Adult Data Unless Noted)

Time to peak: The proportion of samples and subjects with talimogene laherparepvec DNA was highest during cycle 2 for the blood, urine, injection site, and occlusive dressings; highest in cycle 1 for the oral mucosa; and highest in cycles 1 and 2 for the anogenital area. Among patients with detectable talimogene laherparepvec DNA in the blood, urine, oral mucosa, and anogenital area, no samples had detectable DNA 30 days after therapy completion; for those with detectable DNA in injected lesions, no samples had detectable DNA 60 days after therapy completion.

  1. Andtbacka RH, Kaufman HL, Collichio F, et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015;33(25):2780-2788. [PubMed 26014293]
  2. Imlygic (talimogene laherparepvec) [prescribing information]. Thousand Oaks, CA: Amgen Inc; February 2023.
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