dactinomycin

Action and Spectrum

Actions and spectrum: 

dactinomycin is an antineoplastic agent that works by inhibiting DNA and RNA synthesis. It is a cytotoxic antibiotic produced by the bacterium Streptomyces parvulus.

It is a broad spectrum of activity against various tumor types and is used in the treatment of various types of cancer, including Wilms’ tumor, rhabdomyosarcoma, Ewing’s sarcoma, testicular cancer, gestational trophoblastic neoplasia, and childhood tumors.

It is used as a component of multi-agent chemotherapy regimens for the treatment of osteosarcoma and other malignancies. dactinomycin can be used alone or in combination with other anticancer drugs

Drug Interaction

Adverse Reaction

Frequency not defined 

Alopecia 

Dysphagia 

Fever 

Vomiting 

Neutropenia 

Mucositis 

Infection 

Rash 

Fatigue 

Nausea 

Anemia 

Thrombocytopenia 

Hepatotoxicity 

Veno-occlusive disease 

Myelosuppression 

Renal toxicity 

radiation toxicity  

malignancy and leukemia 

Extravasation 

mucocutaneous reactions 

Hepatotoxicity  

Post marketing Reports 

Infections: sepsis with fatal outcome 

Immune system: Hypersensitivity 

Nervous system: Peripheral neuropathy 

Vascular: hemorrhage, Thrombophlebitis 

Gastrointestinal: vomiting, diarrhea, gastrointestinal ulceration, dysphagia, ulcerative stomatitis, proctitis, Nausea, abdominal pain, constipation, cheilitis, esophagitis, ascites, mucositis 

Dermatologic: rash, acne, Stevens-Johnson Syndrome, toxic epidermal necrolysis, Alopecia, dermatitis, erythema multiforme, radiation recall 

Renal and urinary: renal failure, renal impairment 

Hematologic:  leukopenia, pancytopenia, neutropenia, Anemia, thrombocytopenia, reticulocytopenia, febrile neutropenia    

Metabolism and nutrition: hypocalcemia, Anorexia, tumor lysis syndrome 

Ocular: Optic neuropathy 

Respiratory, mediastinal, and thoracic: pneumothorax, Pneumonitis 

Hepatobiliary: hepatomegaly, hepatic failure, hepatitis 

connective and musculoskeletal tissue: growth retardation, Myalgia 

General: fever, Fatigue, malaise

Black Box Warning

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

dactinomycin is contraindicated in patients with a history of hypersensitivity to the drug or any component of the formulation. It is also contraindicated in patients with severe bone marrow depression or suppression.

dactinomycin should not be used in patients with pre-existing renal impairment or hepatic impairment, as it can exacerbate these conditions.

Additionally, it should not be used in pregnant women or in patients who are breastfeeding, as it can cause fetal harm or adverse reactions in nursing infants.  

Caution: 

• Impaired bone marrow function: dactinomycin can cause bone marrow suppression, leading to decreased production of white blood cells, red blood cells, and platelets. Therefore, it should be used cautiously in individuals with bone marrow dysfunction. 
• Renal and hepatic impairment: dactinomycin is mainly metabolized in the liver, and its metabolites are excreted through the kidneys. Therefore, individuals with impaired liver or kidney function should be monitored closely while using dactinomycin. 
• Infections: dactinomycin can suppress the immune system, increasing the risk of infections. Therefore, it should be used cautiously in individuals with current or recent infections. 
• Pregnancy and lactation: dactinomycin can cause harm to the developing fetus and is excreted in breast milk. Therefore, it should not be used in pregnant or breastfeeding individuals unless the benefits outweigh the risks. 
• Previous exposure to anthracyclines or radiation therapy: Previous exposure to anthracyclines or radiation therapy can increase the risk of cardiotoxicity and pulmonary toxicity with dactinomycin use. Therefore, the drug should be used with caution in individuals with previous exposure to these agents.

Comorbidities: 

dactinomycin is used to treat cancer and as such, caution should be taken in patients with comorbidities that may increase the risk of adverse reactions.

These comorbidities may include pre-existing bone marrow depression, liver or kidney impairment, history of heart disease or other cardiac disorders, history of lung disease, and any active infections.

Close monitoring and adjustment of the dosage may be necessary in these patients. Additionally, dactinomycin may cause fetal harm when administered during pregnancy, so caution is also necessary in pregnant patients. 

Pregnancy / Lactation

Pregnancy consideration: pregnancy category D 

Lactation: safety and efficacy not established  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women. 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

dactinomycin is an antineoplastic antibiotic that inhibits DNA-dependent RNA polymerase, thereby inhibiting RNA synthesis and cell growth. It is a member of the actinomycin group of antibiotics, which are produced by the bacterium Streptomyces parvullus. 

dactinomycin binds to the DNA molecule, specifically to the guanine-cytosine base pairs, and intercalates between the base pairs, resulting in the inhibition of RNA transcription. It also causes DNA damage by generating free radicals and reactive oxygen species that can cause DNA strand breaks and other types of damage. 

dactinomycin has a broad spectrum of activity against various types of cancer, including Wilms’ tumor, rhabdomyosarcoma, Ewing’s sarcoma, and other solid tumors, as well as leukemia and other blood cancers.  

Pharmacodynamics: 

dactinomycin is an anti-cancer chemotherapy drug that belongs to the class of medications called anthracyclines. It works by inhibiting the activity of DNA-dependent RNA polymerase, an enzyme that is involved in the transcription of DNA to RNA, thereby inhibiting DNA and RNA synthesis.  

The pharmacodynamics of dactinomycin involve dose-dependent cytotoxicity against rapidly dividing cancer cells. dactinomycin has broad spectrum of activity against a variety of cancers, including Wilms’ tumor, rhabdomyosarcoma, Ewing sarcoma, gestational trophoblastic neoplasms, and certain types of testicular cancer.  

Pharmacokinetics: 

Absorption 

dactinomycin is administered through IV infusion and thus has complete bioavailability. 

Distribution 

dactinomycin is highly protein-bound (94%-97%) and distributes into the tissues rapidly. It has a large volume of distribution (Vd) of approximately 10 L/kg, indicating extensive tissue distribution. 

Metabolism 

dactinomycin undergoes hepatic metabolism and is primarily metabolized by CYP3A4. The major metabolite is an amino acid conjugate, which is excreted in the urine. 

Elimination and excretion 

dactinomycin is primarily eliminated by the liver and excreted in the feces. The elimination half-life of dactinomycin ranges from 20 to 30 hours, indicating a prolonged elimination phase. A small amount of the drug is excreted unchanged in the urine, but most of it is excreted in the feces. 

Adminstartion

Administration: 

dactinomycin is administered intravenously (IV) as an injection or infusion. The dosage and treatment schedule may vary depending on the condition being treated and other factors, such as the patient’s age, weight, and overall health. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: dactinomycin 

Pronounced: [ DAK-tin-oh-MYE-sin ]  

Why do we use dactinomycin? 

dactinomycin is an anti-cancer medication used to treat several types of cancer, including: 

• Wilms’ tumor: a type of kidney cancer that primarily affects children. 
• Rhabdomyosarcoma: a type of cancer that develops from skeletal muscle cells. 
• Ewing sarcoma: a type of cancer that usually affects bones or soft tissue. 
• Testicular cancer: a type of cancer that starts in the testicles. 
• Gestational trophoblastic neoplasia: a type of cancer that develops from the cells that form the placenta during pregnancy. 
• Metastatic non-seminomatous germ cell tumor: a type of cancer that begins in the germ cells, which produce sperm or eggs.