Talimogene laherparepvec

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any signs that you may be developing herpes simplex virus, such as:

• tingling, burning, or pain (especially around your mouth or genitals);
• weakness or cramps in an arm or leg, sometimes with burning pain;
• confusion, severe drowsiness; or
• blisters forming on your fingers or ears, or around your mouth or genitals.

Also call your doctor if you have:

• any skin lesion that will not heal; or
• redness, swelling, warmth, oozing, or skin changes where the injection was given.

Common side effects may include:

• fever, chills, flu-like symptoms;
• feeling tired;
• nausea; or
• pain where the medicine was injected.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Talimogene laherparepvec is a prescription medication used to treat melanoma lesions on the skin and in the lymph nodes. 

It belongs to a group of drugs called oncolytic viruses. These work by replicating inside the cancer cells, causing the cancer cells to burst and die.

This medication is available as an injection and is directly injected into the melanoma lesions. 

Common side effects of talimogene laherparepvec include fatigue, chills, and fever. 

Talimogene Laherparepvec may be found in some form under the following brand names:

• Imlygic

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• anti-herpes viral agents such as acyclovir, famciclovir, or valacyclovir
• steroids or other medications that suppress the immune system

This is not a complete list of talimogene laherparepvec drug interactions. Ask your doctor or pharmacist for more information.

Avoid touching or scratching the areas where this medicine was injected.

The virus contained in talimogene laherparepvec can pass into body fluids (urine, feces, vomit, semen). Avoid allowing your body fluids to come into contact with your hands or other surfaces that cannot be cleaned. Always use a latex condom while having sex. Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Follow your doctor's instructions about how long you should keep using these precautions after your treatment ends.

Antineoplastic agent; a live, attenuated herpes simplex virus type 1 (HSV-1)-derived oncolytic virus encoding granulocyte-macrophage colony-stimulating factor (GM-CSF).1 2 5 8 9 10 11 12

No formal drug interaction studies to date.1

Specific Drugs

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Feeling tired or weak.
• Fever or chills.
• Flu-like signs.
• Headache.
• Dizziness.
• Upset stomach or throwing up.
• Loose stools (diarrhea).
• Hard stools (constipation).
• Belly pain.
• Pain in arms or legs.
• Muscle or joint pain.
• Pain where the shot was given.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• If you need to store talimogene laherparepvec at home, talk with your doctor, nurse, or pharmacist about how to store it.

Dosage adjustment for hepatic impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Concerns related to adverse effects:

• 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; disseminated herpetic infection may occur 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.

• 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. Monitor wounds carefully; infection precautions are recommended, 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. Monitor closely. 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.

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Dose strength: Talimogene laherparepvec is available in two different dose strengths: 106 (1 million) plaque-forming units (PFU) per mL (initial dose only), and 108 (100 million) PFU per mL (all subsequent doses). Verify appropriate dose and vial prior to preparation and administration.

Special handling:

• Hazardous agent: Health care providers who are immunocompromised or pregnant should not prepare or administer talimogene laherparepvec. Accidental talimogene laherparepvec exposure may lead to herpetic infection. Health care providers, close contacts (eg, 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 patients treated with talimogene laherparepvec. Protective gloves should be worn when assisting patients with dressing changes; safely dispose of used dressings, gloves, and cleaning materials. Needle stick and/or splashback to the eyes have been reported during talimogene laherparepvec preparation and administration. If accidently exposed to talimogene laherparepvec, clean the affected area thoroughly with soap and water and/or a disinfectant. Contact a health care provider if signs/symptoms of herpetic infection develop. 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).

Administration Advice:
-This drug should be injected into cutaneous, subcutaneous, and/or nodal lesions that are visible, palpable, or detectable by ultrasound guidance.
-Previously injected and/or uninjected lesion(s) may be injected at subsequent treatment visits.
-It may not be possible to inject all lesions at each treatment visit or over the full course of treatment.
-This drug should only be administered by intralesional injection; IV administration should not be used.
-The manufacturer product information should be consulted for administration technique instructions.

Storage Requirements:
-This drug should be stored and transported at -90 to -70 degrees Celsius (-130 to -94 Fahrenheit).
-Thawed drug should be protected from light and stored in its original vial and carton in a refrigerator at 2 to 8 degrees Celsius (36 to 46 Fahrenheit) for no longer than 12 hours for the 10(6) [1 million] PFU per mL vial, and no longer than 48 hours for the 10(8) [100 million] PFU per mL vial.
-Vials left in the refrigerator longer than the specified times should be discarded.

Preparation/Handling Techniques:
-This drug should be thawed immediately prior to administration; the manufacturer product information should be consulted for thawing instructions.
-Healthcare providers who are immunocompromised or pregnant should not handle, prepare, or administer this drug, and should not come into direct contact with injection sites, dressings, or body fluids of treated patients.
-Personal protective equipment (gown or lab coat, safety glasses or face shield, gloves) should be worn while preparing or administering this drug.
-Accidental drug exposure (especially contact with skin, eyes, mucous membranes) should be avoided and exposed wounds should be covered before handling.
-If accidental occupational exposure occurs, the affected area should be flushed with clean water for at least 15 minutes.
-If exposure to broken skin or needle stick occurs, the affected area should be cleaned thoroughly with soap and water and/or a disinfectant.
-All drug spills should be treated with a virucidal agent (e.g., 1% sodium hypochlorite) and blotted with absorbent materials.
-All materials that come in contact with this drug should be disposed of in accordance with universal biohazard precautions.

General:
-Treatment with this drug should be reinitiated if new unresectable cutaneous, subcutaneous, or nodal lesions appear after a complete response.
-This drug has not been shown to improve overall survival or have an effect on visceral metastases.
-There is no clinical overdose experience with this drug; suspected overdoses should be treated symptomatically with supportive measures instituted as required.
-This drug is provided as a sterile frozen suspension in 1 mL single-use vials in 2 different dose strengths: 10(6) [1 million] PFU per mL (light green cap) for initial dose only, and 10(8) [100 million] PFU per mL (royal blue cap) for all subsequent doses.
-Each drug vial may contain residual components of VERO cells including DNA, protein, and trace quantities of fetal bovine serum.

Patient Advice:
Following are some recommendations on how to prevent spreading this drug to other areas of your body and to your close contacts; talk to your healthcare provider about other ways to prevent accidental drug exposure.
-Avoid direct contact between your treatment sites/dressings/bodily fluids and your close contacts (for example, do not kiss a close contact if either person has an open mouth sore);
-Wear gloves while putting on or changing your dressings;
-Keep treatment sites covered with airtight and watertight dressings for at least 1 week after each treatment (or longer if the treatment site is weeping or oozing);
-Replace dressings right away if they come loose or fall off;
-Place all used dressings and cleaning materials in a sealed plastic bag before throwing them away in the garbage;
-Avoid touching or scratching your treatment sites.