Lyovac Cosmegen

A compound composed of a two cyclic peptides attached to a phenoxazine that is derived from streptomyces parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after Lyovac Cosmegen therapy. (From AMA Drug Evaluations Annual, 1993, p2015)

Lyovac Cosmegen, as part of a combination chemotherapy and/or multi-modality treatment regimen, is indicated for the treatment of Wilms’ tumor, childhood rhabdomyosarcoma, Ewing’s sarcoma and metastatic, nonseminomatous testicular cancer.

Lyovac Cosmegen is indicated as a single agent, or as part of a combination chemotherapy regimen, for the treatment of gestational trophoblastic neoplasia.

Lyovac Cosmegen, as a component of regional perfusion, is indicated for the palliative and/or adjunctive treatment of locally recurrent or locoregional solid malignancies.

Lyovac Cosmegen injection is used to treat certain types of cancer. This includes cancer of the bones and soft tissue (including muscles and tendons), Wilms' tumor (a cancer of the kidney found primarily in children), tumors in the uterus or womb, and cancer of the testicles.

Lyovac Cosmegen interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by Lyovac Cosmegen, other effects will also occur. Some of these may be serious and must be reported to your doctor. Other effects, like hair loss, may not be serious but may cause concern. Some effects may not occur for months or years after the medicine is used.

Before you begin treatment with Lyovac Cosmegen, you and your doctor should talk about the benefits Lyovac Cosmegen will do as well as the risks of using it.

Lyovac Cosmegen is to be administered only by or under the immediate supervision of your doctor.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, Lyovac Cosmegen is used in certain patients with the following medical conditions:

• Kaposi's sarcoma (a type of cancer of the skin and mucous membranes).
• Osteosarcoma (a type of bone cancer found primarily in children).

Not for oral administration: Toxic reactions due to Lyovac Cosmegen are frequent and may be severe, thus limiting in many instances the amount that may be administered. However, the severity of toxicity varies markedly and is only partly dependent on the dose employed.

Careful calculation of the dosage should be performed prior to administration of each dose.

Intravenous Use: The dosage of Lyovac Cosmegen varies depending on the tolerance of the patient, the size and location of the neoplasm, and the use of other forms of therapy. It may be necessary to decrease the usual dosages suggested below when additional chemotherapy or radiation therapy is used concomitantly or has been used previously.

The dosage for Lyovac Cosmegen is calculated in micrograms (mcg). The dose intensity per 2-week cycle for adults or children should not exceed 15 mcg/kg/day or 400-600 mcg/m2/day intravenously for five days. Calculation of the dosage for obese or edematous patients should be performed on the basis of surface area in an effort to more closely relate dosage to lean body mass.

A wide variety of single agent and combination chemotherapy regimens with Lyovac Cosmegen may be employed. Because chemotherapeutic regimens are constantly changing, dosing and administration should be performed under the direct supervision of physicians familiar with current oncologic practices and new advances in therapy. The following suggested regimens are based upon a review of current literature concerning therapy with Lyovac Cosmegen and are on a per cycle basis.

Wilms’ Tumor, Childhood Rhabdomyosarcoma and Ewing’s Sarcoma: Regimens of 15 mcg/kg intravenously daily for five days administered in various combinations and schedules with other chemotherapeutic agents have been utilized in the treatment of Wilms’ tumor, rhabdomyosarcoma and Ewing’s sarcoma.

Metastatic Nonseminomatous Testicular Cancer: 1000 mcg/m2 intravenously on Day 1 as part of a combination regimen with cyclophosphamide, bleomycin, vinblastine, and cisplatin.

Gestational Trophoblastic Neoplasia: 12 mcg/kg intravenously daily for five days as a single agent.

500 mcg intravenously on Days 1 and 2 as part of a combination regimen with etoposide, methotrexate, folinic acid, vincristine, cyclophosphamide and cisplatin.

Regional Perfusion in Locally Recurrent and Locoregional Solid Malignancies: The dosage schedules and the technique itself vary from one investigator to another; the published literature, therefore, should be consulted for details. In general, the following doses are suggested:

50 mcg (0.05 mg) per kilogram of body weight for lower extremity or pelvis.

35 mcg (0.035 mg) per kilogram of body weight for upper extremity.

It may be advisable to use lower doses in obese patients, or when previous chemotherapy or radiation therapy has been employed.

Preparation of Solution for

Intravenous Administration: This drug is HIGHLY TOXIC and both powder and solution must be handled and administered with care. Since Lyovac Cosmegen is extremely corrosive to soft tissues, it is intended for intravenous use. Inhalation of dust or vapors and contact with skin or mucous membranes, especially those of the eyes, must be avoided. Appropriate protective equipment should be worn when handling Lyovac Cosmegen. Should accidental eye contact occur, copious irrigation for at least 15 minutes with water, normal saline or a balanced salt ophthalmic irrigating solution should be instituted immediately, followed by prompt ophthalmologic consultation. Should accidental skin contact occur, the affected part must be irrigated immediately with copious amounts of water for at least 15 minutes while removing contaminated clothing and shoes. Medical attention should be sought immediately. Contaminated clothing should be destroyed and shoes cleaned thoroughly before reuse.

Reconstitute Lyovac Cosmegen by adding 1.1 mL of Sterile Water for Injection (without preservative) using aseptic precautions. The resulting solution of Lyovac Cosmegen will contain approximately 500 mcg (0.5 mg) per mL.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. When reconstituted, Lyovac Cosmegen is a clear, gold-colored solution.

Once reconstituted, the solution of Lyovac Cosmegen can be added to infusion solutions of Dextrose Injection 5 percent or Sodium Chloride Injection either directly or to the tubing of a running intravenous infusion.

Although reconstituted Lyovac Cosmegen is chemically stable, the product does not contain a preservative and accidental microbial contamination might result. Any unused portion should be discarded. Use of water containing preservatives (benzyl alcohol or parabens) to reconstitute Lyovac Cosmegen for Injection, results in the formation of a precipitate.

Studies conducted on Lyovac Cosmegen lyophilized powder for injection demonstrate that drug product diluted at concentrations of 10 mcg/mL or higher in WFI, 0.9% saline and 5% dextrose in glass or PVC infusion containers are chemically stable for up to 10 hours when stored at ambient room temperature. Drug product diluted to concentrations lower than 10 mcg/mL and stored at ambient room temperature showed significantly lower recoveries. Therefore, only drug product diluted at concentrations greater than 10 mcg/mL are recommended for administration. Since the product contains no preservatives, the final prepared product (which has undergone reconstitution and dilution) must be used within 4 hours of initial reconstitution when stored at ambient room temperature.

Partial removal of Lyovac Cosmegen from intravenous solutions by cellulose ester membrane filters used in some intravenous in-line filters has been reported.

Since Lyovac Cosmegen is extremely corrosive to soft tissue, precautions for materials of this nature should be observed.

If the drug is given directly into the vein without the use of an infusion, the “two-needle technique” should be used. Reconstitute and withdraw the calculated dose from the vial with one sterile needle. Use another sterile needle for direct injection into the vein.

Discard any unused portion of the Lyovac Cosmegen solution.

Management of Extravasation: Care in the administration of Lyovac Cosmegen will reduce the chance of perivenous infiltration. It may also decrease the chance of local reactions such as urticaria and erythematous streaking. On intravenous administration of Lyovac Cosmegen, extravasation may occur with or without an accompanying burning or stinging sensation, even if blood returns well on aspiration of the infusion needle. If any signs or symptoms of extravasation have occurred, the injection or infusion should be immediately terminated and restarted in another vein. If extravasation is suspected, intermittent application of ice to the site for 15 minutes 4 times daily for 3 days may be useful. The benefit of local administration of drugs has not been clearly established. Because of the progressive nature of extravasation reactions, close observation and plastic surgery consultation is recommended. Blistering, ulceration and/or persistent pain are indications for wide excision surgery, followed by split-thickness skin grafting.

See also:
What is the most important information I should know about Lyovac Cosmegen?

Do not use Lyovac Cosmegen if you are pregnant. It could harm the unborn baby.

Do not receive a "live" vaccine while using Lyovac Cosmegen, and avoid coming into contact with anyone who has recently received a live vaccine. There is a chance that the virus could be passed on to you. Live vaccines include measles, mumps, rubella (MMR), Bacillus Calmette-Guérin (BCG), oral polio, rotavirus, smallpox, typhoid, yellow fever, varicella (chickenpox), H1N1 influenza, and nasal flu vaccine.

You should not receive Lyovac Cosmegen if you are allergic to it, or if you have recently had chickenpox or herpes zoster (shingles).

To make sure you can safely use Lyovac Cosmegen, tell your doctor if you have recently received radiation treatment for Wilms' tumor.

Tell your caregivers if you feel any burning, pain, or swelling around the IV needle when Lyovac Cosmegen is injected.

Lyovac Cosmegen can lower blood cells that help your body fight infections. Your blood may need to be tested often. Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Use Lyovac Cosmegen as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Lyovac Cosmegen is usually given as an injection at your doctor's office, hospital, or clinic. Ask your doctor or pharmacist any questions you may have about Lyovac Cosmegen.
• If you get Lyovac Cosmegen in your eyes or on your skin, rinse the area with water for 15 minutes. Remove any contaminated clothing and do not reuse. Contaminated shoes must be cleaned completely before reuse.
• When mixed, Lyovac Cosmegen is a clear, gold-colored solution. Do not use it if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.
• Keep this product, as well as syringes and needles, out of the reach of children and pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.
• If you miss a dose of Lyovac Cosmegen, contact your doctor right away.

Ask your health care provider any questions you may have about how to use Lyovac Cosmegen.

Lyovac Cosmegen is used alone or with other anti-cancer drugs to treat cancer. It works by slowing or stopping the growth of cancer cells.

How to use Lyovac Cosmegen intravenous

This medication is given by injection into a vein over a few minutes by a health care professional, usually once daily for 1 to 5 days or as directed by your doctor. Do not give into a muscle or under the skin. Tell your doctor or nurse right away if you experience pain, burning, or redness at the injection site.

Dosage is based on your medical condition, body size, and response to treatment. Your doctor will order lab tests to make sure you can receive your next dose. Keep all medical/lab appointments.

See also:
What other drugs will affect Lyovac Cosmegen?

Drug/LaboratoryTest Interactions

Lyovac Cosmegen D may interfere with bioassay procedures for the determination of antibacterial drug levels.

See also:
What are the possible side effects of Lyovac Cosmegen?

Applies to Lyovac Cosmegen: intravenous powder for solution

In addition to its needed effects, some unwanted effects may be caused by Lyovac Cosmegen (the active ingredient contained in Lyovac Cosmegen). In the event that any of these side effects do occur, they may require medical attention.

If any of the following side effects occur while taking Lyovac Cosmegen, check with your doctor or nurse immediately:

More common:

• Black, tarry stools
• blood in the urine or stools
• cough or hoarseness accompanied by fever or chills
• diarrhea (continuing)
• difficulty with swallowing
• fever or chills
• heartburn
• lower back or side pain accompanied by fever or chills
• painful or difficult urination accompanied by fever or chills
• pinpoint red spots on the skin
• sores in the mouth and on the lips
• stomach pain (continuing)
• unusual bleeding or bruising
• unusual tiredness or weakness

• Joint pain
• pain at the injection site
• swelling of the feet or lower legs
• wheezing
• yellow eyes or skin

• Abdominal or stomach cramps
• blisters
• body aches or pain
• chapped, red, or swollen lips
• confusion
• congestion
• convulsions
• cough
• difficulty with breathing
• difficulty with moving
• difficulty with swallowing
• dryness or soreness of the throat
• flushing or redness of the skin
• growth retardation
• irregular heartbeats
• muscle aching or cramping
• muscle cramps in the hands, arms, feet, legs, or face
• muscle pains or stiffness
• numbness and tingling around the mouth, fingertips, or feet
• runny nose
• scaling, redness, burning, pain, or other signs of inflammation of the lips
• shortness of breath
• swollen joints
• tender, swollen glands in the neck
• tremor
• unusually warm skin
• voice changes

Minor Side Effects

Some of the side effects that can occur with Lyovac Cosmegen may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common:

• Darkening of the skin
• general feeling of discomfort or weakness
• nausea and vomiting
• skin rash or acne
• unusual feeling of dullness or sluggishness