Dactinomycin

What is Dactinomycin?

• Dactinomycin, (Cosmegen) also known as actinomycin D, is an actinomycin used to treat Ewing sarcoma, gestational trophoblastic tumor, Wilms tumor, and certain types of testicular cancer.
• It is also used to treat rhabdomyosarcoma in children.
• It is being studied in the treatment of other types of cancer.
• Dactinomycin comes from the bacterium Streptomyces parvulus.

Dactinomycin structure

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Dactinomycin mechanism

What are the uses of this medicine?

Dactinomycin (Cosmegen) is used alone or with other drugs to treat:

• Ewing sarcoma in adults and children.
• Gestational trophoblastic disease in adults and children.
• Rhabdomyosarcoma in adults and children.
• Solid tumors that are locally recurrent. It is used as palliative and/or adjuvant therapy in adults.
• Testicular cancer. It is used in adults and children whose nonseminomas have metastasized (spread to other parts of the body).
• Wilms tumor in adults and children.

How does this medicine work?

• Dactinomycin (dak” tin oh mye’ sin) is one of the actinomycins, anticancer antibiotics that were discovered by Selman Waksman and colleagues in the 1940s using fermentation exacts from bacteria (Streptomyces).
• The actinomycins are chromopeptides which bind to double-helical DNA and interrupt RNA transcription, causing cell arrest and inhibition of cell division.
• Actinomycin D, later named dactinomycin, was isolated from Streptococcus parvulus and was identified as a promising antineoplastic agent.
• Subsequently, dactinomycin was shown to have antitumor effect against a broad array of solid tumors.

Who Should Not Use this medicine ?

• This medicine have no usage limitations.

What drug interactions can this medicine cause?

• No formal drug interaction studies have been conducted with Dactinomycin.

Is this medicine FDA approved?

• Dactinomycin was formally approved for use in the United States in 1964 and continues to be a valuable agent in the therapy of solid tumors of childhood (Wilms tumor, rhabdomyosarcoma) and in choriocarcinoma in adult women.

How should this medicine be used?

Recommended dosage: Wilms Tumor:

• The recommended dose is 45 mcg/kg intravenously once every 3 to 6 weeks for up to 26 weeks, as part of a multi-agent combination chemotherapy regimen.

Rhabdomyosarcoma:

• The recommended dose is 15 mcg/kg intravenously once daily for 5 days every 3 to 9 weeks for up to 112 weeks, as part of a multi-agent combination chemotherapy regimen.

Ewing Sarcoma:

• The recommended dose is 1250 mcg/m 2 intravenously once every 3 weeks for 51 weeks, as part of a multi-agent combination chemotherapy regimen.

Metastatic Nonseminomatous Testicular Cancer:

• The recommended dose is 1000 mcg/m 2 intravenously every 3 weeks, as part of cisplatin-based, multi-drug chemotherapy regimen.

Gestational Trophoblastic Neoplasia:

• Non-metastatic and Low-risk Metastatic Disease: The recommended dose is 12 mcg/kg intravenously daily for 5 days, as a single agent.
• High-risk Metastatic Disease: The recommended dose is 500 mcg intravenously on Days 1 and 2 every 2 weeks for up to 8 weeks, as part of a multi-agent combination chemotherapy regimen.

Regional Perfusion in Locally Recurrent and Locoregional Solid Malignancies:

• Lower Extremity or Pelvis: The recommend dose is 50 mcg/kg once with melphalan.
• Upper Extremity: The recommended dose is 35 mcg/kg once with melphalan.

Administration:

• Administer the diluted reconstituted product intravenously over 10 to 15 minutes.
• Do not use in-line filters with a cellulose ester membrane.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form: As injection: 500 mcg as a lyophilized powder in a single-dose vial.

This medicine is available in fallowing brand namesː

• Cosmegen

What side effects can this medication cause?

The most common side effects of this medicine include:

• infection
• alopecia
• rash
• dysphagia
• fatigue
• fever
• nausea
• vomiting
• anemia
• neutropenia
• thrombocytopenia
• mucositis
• hepatotoxicity

What special precautions should I follow?

• The risk of developing secondary malignancies, including leukemia, is increased following treatment with Cosmegen.
• Severe and fatal hepatic veno-occlusive disease (VOD) can occur with Cosmegen. Monitor for elevations in AST, ALT, total bilirubin, hepatomegaly, weight gain, or ascites. Consider delaying next dose.
• Extravasation of Cosmegen can result in severe local tissue injury manifesting as blistering, ulcerations and persistent pain requiring wide excision surgery followed by split-thickness skin grafting. Immediately interrupt the injection or infusion and apply ice.
• Severe and fatal myelosuppression, which may include neutropenia, thrombocytopenia and anemia, can occur with Cosmegen. Monitor blood cell counts before each cycle. Delay next dose if severe myelosuppression has not improved.
• The safety with live viral vaccines following Cosmegen has not been studied and vaccination with live virus vaccines is not recommended before or during treatment.
• Severe mucocutaneous reactions, such as Steven-Johnson syndrome and Toxic Epidermal Necrolysis (TEN), can occur with Cosmegen. Permanently discontinue Cosmegen in patients who experience a severe mucocutaneous reaction.
• Abnormalities of renal function can occur with Cosmegen. Monitor creatinine and electrolytes frequently during Cosmegen therapy.
• Hepatotoxicity can occur with Cosmegen. Monitor AST, ALT, alkaline phosphatase, and bilirubin prior to and during Cosmegen therapy.
• Cosmegen can increase radiation-induced gastrointestinal toxicity, myelosuppression, or erythema and vesiculation of the skin or buccal and pharyngeal mucosa. Reduce dose by 50% during concomitant radiation. Use caution when administering within two months of radiation.
• Based on findings from animal studies and its mechanism of action, Cosmegen can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus and to use effective contraception.

What to do in case of emergency/overdose?

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.

Can this medicine be used in pregnancy?

• Based on findings from animal studies and its mechanism of action, Cosmegen can cause fetal harm when administered to a pregnant woman.

Can this medicine be used in children?

• The safety and effectiveness of dactinomycin have been established in pediatric patients with Wilms tumor, rhabdomyosarcoma, Ewing sarcoma, and metastatic nonseminomatous testicular cancer .
• The safety and effectiveness of dactinomycin have been established in post-menarchal pediatric patients with gestational trophoblastic neoplasia.
• The safety and effectiveness of Cosmegen have not been established in pediatric patients undergoing regional perfusion for locally recurrent or locoregional solid malignancies.

What are the active and inactive ingredients in this medicine?

Active ingredients:

• DACTINOMYCIN

Inactive ingredients:

• MANNITOL

Who manufactures and distributes this medicine?

• Manufactured by: Baxter Oncology GmbH, 33790 Halle/Westfalen, Germany
• Manufactured for: Recordati Rare Diseases Inc., Lebanon, NJ, U.S.A.
• Cosmegen is a registered trademark of Recordati Rare Diseases Inc.

What should I know about storage and disposal of this medication?

• Store at 20 to 25ºC (68 to 77ºF); excursions permitted between 15 to 30ºC (59 to 86ºF).
• Protect Cosmegen from light and humidity.
• Store the reconstituted Cosmegen at room temperature for no more than 4 hours from reconstitution to completion of administration.
• Cosmegen is a cytotoxic drug.
• Follow applicable special handling and disposal procedures.

• Dailymed label info on Dactinomycin
• FDA Dactinomycin

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