Daktinomycin - instructions for use, doses, side effects, contraindications

Clinical and pharmacological group: & nbsp

Antineoplastic antibiotics

Included in the formulation

Aknomid®

solution in / in d / perfusion

Adikom, Open Company Russia

Dactinomycin

lyophilizate in / in d / perfusion

OMUTNINSK SCIENTIFIC EXPERIMENTAL-INDUSTRIAL BASE, OJSC Russia

Cosmogen®

lyophilizate for injections

Orphan Europe France

АТХ:

L.01.D.A.01 Dactinomycin

L.01.D.A Actinomycins

Pharmacodynamics:

This drug is an actinomycin antibiotic.

The drug is inserted into a double helix of DNA between guanine and cytisine, forming a stable complex of dactinomycin-DNA. This complex inhibits the activity of DNA-dependent RNA polymerase, which disrupts the synthesis of RNA and as a result, transcription, at high doses dactinomycin can also violate DNA synthesis. In addition, the drug is able to damage the structure of the DNA chain, affecting the enzyme topoisomerase II, and also releasing free radicals.

The drug also exhibits immunosuppressive, antibacterial and antifungal activity.

Pharmacokinetics:

It is not practically metabolized, does not penetrate the blood-brain barrier, penetrates the placenta, accumulates in nuclear cells. Half-life is 36 hours. It is excreted slowly from the body, mostly through the gastrointestinal tract (30%), partially with urine (10%). Excreted unchanged.

Indications:

Rhabdomyosarcoma, Wilms tumor, choriocarcinoma, uterine body cancer, Gram-negative sarcoma, Ewing's tumor, melanoma, Kaposi's sarcoma, metastatic nonsemic carcinoma of the testicles.

ICD-10

II.C40-C41.C40 Malignant neoplasm of bones and articular cartilages of extremities

II.C40-C41.C41 Malignant neoplasm of bones and articular cartilages of other and unspecified sites

II.C40-C41.C41.9 Malignant neoplasm of bones and articular cartilage, unspecified

II.C43-C44.C43.9 Malignant melanoma of skin, unspecified

II.C43-C44 Melanoma and other malignant neoplasms of the skin

II.C45-C49.C46 Kaposi's Sarcoma

II.C45-C49.C49 Malignant neoplasm of other types of connective and soft tissue

II.C51-C58.C54 Malignant neoplasm of uterine body

II.C51-C58.C56 Malignant neoplasm of ovary

II.C51-C58.C58 Malignant neoplasm of placenta

II.C60-C63.C62 Malignant neoplasm of testis

II.C64-C68.C64 Malignant neoplasm of kidney, except for renal pelvis

II.D37-D48.D39.2 Neoplasm of the placenta

XV.O00-O08.O01 Bumpy drift

Contraindications:

Herpes zoster, hypersensitivity to the drug, age less than 12 months, chicken pox, oppression of bone marrow function,marked cytopenic reaction in drug or radiation therapy (history), liver disease, liver failure, hyperuricemia, pregnancy, breastfeeding.

Carefully:

In patients older than 65 years (increased risk of myelosuppression), gout, hyperuricemia, nephrolithiasis (including urate), with previous cytotoxic or radiotherapy, simultaneous administration with live viral vaccines.

Pregnancy and lactation:

Category FDA - D. In view of the potential threat to the fetus (side effects, mutagenicity, carcinogenicity and teratogenicity), it is recommended that women of childbearing age during treatment with dactinomycin use contraceptives. Penetrates through the placental barrier. Possible development of fetal side effects observed in adults. In the presence of indications, it is necessary to relate the risk and benefit and take into account the mutagenic, carcinogenic and teratogenic potentials of this drug. There is no information on the penetration into breast milk. In view of the excretion of other antitumor drugs by milk and the potential risk of unwanted effects on the child (side effects, mutagenicity,carcinogenicity) during treatment with dactinomycin, breast-feeding should be discontinued.

Dosing and Administration:

Intravenously.

Intravenous infusion administration of the drug should be carried out only in a hospital.

Doses are calculated individually depending on the age, the patient's condition, the plan of therapeutic measures, as well as the personal characteristics of the patient.

The daily dose for both adults and children should not exceed 15 mcg / kg or 400-600 mcg / m² for 5-7 days. Usually, the adult dose is 500 μg per day intravenously for a maximum of 5-7 days.

Side effects:

From the skin: skin rash, alopecia, acne.

From the gastrointestinal tract: abdominal pain, vomiting, nausea, esophagitis, cheilitis, anorexia, ulcerative stomatitis, diarrhea, dysphagia, proctitis, erosive-ulcerative lesions of the gastrointestinal tract.

On the part of the reproductive system: amenorrhea, azoospermia.

From the side of the circulatory system: leukopenia, pancytopenia, thrombocytopenia, agranulocytosis, reticulocytopenia.

Local reactions: necrosis of tissues.

Other: hyperuricemia, nephropathy, general malaise, muscle pain, fever, lethargy, hypocalcemia.

Overdose:

Symptoms: nausea, vomiting, diarrhea, stomatitis, gastrointestinal ulcers, severe hematopoietic suppression, acute renal failure, possible fatal outcome. Treatment is symptomatic.

Interaction:

With simultaneous administration with drugs that have a myelotoxic effect, the drug increases their toxic effect.

With the simultaneous administration of dactinomycin with uricosuric drugs, there is a risk of developing nephropathy.

With the simultaneous administration of the drug with doxorubicin, its cardiotoxic effect may be intensified.

Dactinomycin weakens the immune response to the introduction of inactivated viral vaccines; against the background of therapy with the use of this drug should refrain from vaccination with live viral vaccines. In addition, the use of dactinomycin weakens the effect of vitamin K.

Special instructions:

Treatment is carried out under the strict supervision of a doctor who has experience working with antitumour agents.

When treating this drug, it is necessary to monitor the activity of hepatic transaminases, bilirubin, uric acid, kidney function, platelets, hematocrit, hemoglobin, and the state of the oral cavity.

To avoid deferred side effects, which can occur 2-4 days after taking the drug, it is prescribed by short courses.

On the background of therapy, it is not recommended to vaccinate the patient and his family members.

Influence on the ability to drive vehicles and mechanisms.

Since the drug is able to influence the central nervous system (feeling tired, dizzy), during the period of treatment it is necessary to refrain from driving vehicles and from practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Instructions

Dactinomycin (Dactinomycinum)