Trepar

Trepar

dactinomycin

Manufacturer:

Korea United Pharma

Distributor:

Qualimed
Full Prescribing Info
Contents
Dactinomycin.
Description
Each 1 mL reconstituted solution contains: Dactinomycin, USP 500 mcg.
Action
Pharmacology: Pharmacodynamics: Mode of Action: 'Cosmegen' inhibits the proliferation of cells by forming a stable complex with DNA and interfering with DNA-dependent RNA synthesis.
Generally, the actinomycins exert an inhibitory effect on Gram-positive and Gram-negative bacteria and on some fungi. However, the toxic properties of the actinomycins (including dactinomycin) in relation to antibacterial activity are such as to preclude their use as antibiotics in the treatment of infectious diseases.
Because the actinomycins are cytotoxic, they have an antineoplastic effect which has been demonstrated in experimental animals with various types of tumour implant. This cytotoxic action is the basis for their use in the palliative treatment of certain types of cancer.
Pharmacokinetics: Dactinomycin is poorly absorbed from GIT; thus, it should be IV administered. It is rapidly distributed into tissues, with high concentrations in bone marrow and nucleated cells, including granulocytes and lymphocytes. Dactinomycin also crosses the placenta but crosses the blood-brain barrier poorly. Metabolism of the drug is minimal. Excretion of the drug is mainly in bile and urine.
Indications/Uses
Dactinomycin is indicated in the treatment of the following conditions: Wilms' tumor; Rhabdomyosarcoma; Carcinoma of testis and uterus; Other neoplasms.
Dosage/Direction for Use
Dactinomycin is toxic and the severity of toxicity is dependent on the dosage employed. Therefore, the drug must be given in short courses.
Intravenous Use: The dosage of Dactinomycin 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 other chemotherapy or x-ray therapy is used concomitantly or has been used previously.
The dosage for adults or children should not exceed 15 μg (potency)/kg or 0.4-0.6 mg (potency)/m2 of body surface daily intravenously for five days. Calculation of the dosage for obese or edematous patients should be on the basis of surface area in an effect to relate dosage to lean body mass.
Adults: The usual adult dosage is 0.5 mg (potency) daily intravenously for a maximum of five days.
Children: In children 15 μg (potency) per kg of body weight is given intravenously daily for five days. An alternative schedule is a total dosage of 2.5 mg (potency) per m2 of body surface given intravenously over a one-week period.
In both adults and children, a second course may be given after at least three weeks have lapsed, provided all signs of toxicity have disappeared.
Reconstitution: Reconstitute Dactinomycin by adding 1.1 mL of Sterile Water for Injection (without preservative) under aseptic conditions. The resulting solution of Dactinomycin will contain approximately 0.5 mg/mL.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit (When reconstituted, Dactinomycin is a clear, gold-colored solution).
Once reconstituted, the solution of Dactinomycin can be added to infusion solutions of 5% Dextrose Injection or Sodium Chloride Injection either directly or to the tubing of a running intravenous infusion.
Although reconstituted, Dactinomycin is chemically stable. The product does not contain a preservative, and thus, care must be taken to assure the sterility of prepared solutions. Any unused portion should be discarded. Use of water which contains any preservative (benzyl alcohol or parabens) to reconstitute Dactinomycin for Injection results in the formation of a precipitate.
Partial removal of Dactinomycin from intravenous solutions by cellulose ester membrane filters used in some intravenous in-line filters has been reported.
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 Dactinomycin solution.
The reconstituted solution is stable at room temperature; however, this solution contains no preservative so it has been suggested that unused portions of the injection be discarded.
Isolation-Perfusion Technique: The dosage schedules and the technique itself are as follows: 50 μg (potency) per kg of body weight for lower extremity or pelvis.
35 μg (potency) per kg 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.
Complications of the perfusion technique are related mainly to the amount of drug that escapes into the systemic circulation and may consist of hemopoietic depression, absorption of toxic products from massive destruction of neoplastic tissue, increased susceptibility to infection, impaired wound healing, and superficial ulceration of the gastric mucosa. Other side effects may include edema of the extremity involved, damage to soft tissues of the perfused area, and (potentially) venous thrombosis.
Overdosage
In the event of overdosage, dactinomycin therapy should be withdrawn immediately. Limited information is available on overdosage in humans. Manifestations of overdose have included nausea, vomiting, diarrhoea, mucositis including stomatitis, gastrointestinal ulceration, severe skin disorders including skin exfoliation, exanthema, desquamation and epidermolysis, severe haemopoietic depression, veno-occlusive disease, acute renal failure, sepsis (including neutropenic sepsis) with fatal outcome and death. Treatment should be symptomatic and supportive. There is no known antidote. It is advisable to check skin and mucous membrane integrity as well as renal, hepatic and bone-marrow functions frequently.
Contraindications
Hypersensitivity to Dactinomycin. Patients with chicken pox; herpes zoster; severe generalized disease (fatal systemic impairment may occur).
Pregnancy.
Special Precautions
Dactinomycin should be used with caution in the following: Patients with hepatic impairment; renal impairment; bone marrow suppression; complicated infections.
Dactinomycin should not be administered subcutaneously or intramuscularly.
When this drug is administered intravenously, care should be taken to avoid extravasation.
Dactinomycin should be administered only under the supervision of a physician who is experienced in the use of cancer chemotherapeutic agents.
This drug is highly toxic and both powder and solution must be handled and administered with care. Inhalation of dust or vapors and contact with skin or mucous membranes, especially those of the eyes, must be avoided. Should accidental eye contact occur, copious irrigation with water should be instituted immediately, followed by prompt ophthalmologist consultation. Should accidental skin contact occur, the affected part must be irrigated immediately with copious amounts of water for at least 15 minutes.
As with all antineoplastic agents, Dactinomycin is a toxic drug; therefore, frequent observations of the patient for adverse reactions are necessary. These reactions may involve any tissue of the body. The possibility of an anaphylactoid reaction should be borne in mind.
Particular caution is necessary when administering Dactinomycin within two months of irradiation for the treatment of right-sided Wilms' tumor, since hepatomegaly and elevated SGOT levels have been noted.
Nausea and vomiting due to Dactinomycin make it necessary to give this drug intermittently. It is extremely important to observe the patient daily for toxic side effects when multiple chemotherapy is employed, since a full course of therapy occasionally, is not tolerated.
If stomatitis, diarrhea or severe hemopoietic depression appear during therapy, Dactinomycin should be discontinued until the patient has recovered.
Recent reports indicate an increased incidence of second primary tumors following treatment with radiation and antineoplastic agents, such as Dactinomycin. Multi-modal therapy creates the need for careful, long-term observation of cancer survivors.
Many abnormalities of renal, hepatic, and bone marrow function have been reported in patients with neoplastic disease receiving Dactinomycin. It is advisable to check renal, hepatic and bone marrow functions frequently.
It has been reported that Dactinomycin may interfere with bioassay procedures for the determination of antibacterial drug levels.
Bleeding may be indicative of the presence of an infection.
Carcinogenicity, Mutagenicity or Impairment of Fertility: It has been proven that Dactinomycin is a positive carcinogen in animals. Local sarcomas were produced in mice and rats after repeated subcutaneous or intraperitoneal injection. Studies have demonstrated that mesenchymal tumor has developed when Dactinomycin is administered to a rabbit intraperitoneally. Dactinomycin has been shown to be mutagenic in a number of test systems in vitro and in vivo including human fibroblasts, leucocytes and HELA cells. DNA damage and cytogenetic effects have been observed in mice and rats. Studies in animals (rat, intraperitoneal administration) have reported the occurrence of spermatogenic depression.
Use in Pregnancy & Lactation: Pregnancy Category C.
Dactinomycin has been shown to cause malformations and embryotoxicity in rats, rabbits and hamsters when given in doses of 50-100 μg/kg intravenously (3-7 times the maximum recommended human dose).
There are no adequate and well-controlled studies in pregnant women. Dactinomycin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
It is not known whether Dactinomycin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Dactinomycin, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Use in Children: The greater frequency of toxic effects of Dactinomycin in infants suggests that this drug should be given to infants only over the age of 12 months.
Use in children or patients of childbearing potential should be considered because of the possible effect on the gonads.
Use In Pregnancy & Lactation
Pregnancy Category C.
Dactinomycin has been shown to cause malformations and embryotoxicity in rats, rabbits and hamsters when given in doses of 50-100 μg/kg intravenously (3-7 times the maximum recommended human dose).
There are no adequate and well-controlled studies in pregnant women. Dactinomycin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
It is not known whether Dactinomycin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Dactinomycin, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Adverse Reactions
Dermatological Problems: Alopecia, skin eruptions, acne and flare-up of erythema or increased pigmentation of previously irradiated skin.
Gastrointestinal disturbances: Anorexia, nausea & vomiting, abdominal pain, diarrhea, stomatitis, proctitis, gastrointestinal ulceration, liver toxicity including ascites, hepatomegaly, hepatitis and liver function test abnormalities. Nausea and vomiting, which occur during the first few hours after administration may be alleviated by giving antiemetics.
Toxic effects (except nausea and vomiting) usually do not become apparent until two to four days after a course of therapy is stopped.
Renal Problems:
Renal abnormalities and rarely, increase of BUN may occur.
Hematological Problems: Anemia, even to the point of aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia, pancytopenia and reticulopenia may occur. Platelet and white cell counts should be done daily to detect severe hemopoietic depression. If either count markedly decreases, the drug should be withheld to allow marrow recovery. This often takes up to three weeks.
Hepatic Abnormalities: Hepatotoxicity including ascites, hepatomegaly, hepatitis, liver function test abnormalities and occasionally, jaundice may occur.
Hypersensitivity Reactions: Occasionally, dyspnea and anaphylaxis may occur.
Neurotoxicity: Hypernoia, headache, heaviness in head, malaise, fatigue, debility, occasionally, numbness of extremities, convulsion, dizziness, apprehension and rarely, lethargy may occur.
Local: Phlebitis at IV site.
Others: Nasal hemorrhage, fever, occasionally malaise, myalgia, flush, sputum cruentum, hematochezia, compression of pectus, blepharedema, pharyngitis, proctitis and hypocalcemia may occur.
Dactinomycin is extremely corrosive. If extravasation occurs during intravenous use, severe damage to soft tissues will occur. In at least one instance, this has led to contracture of the arms.
Drug Interactions
Concomitant administration with radiation therapy or other antineoplastic agents may increase the effect of Dactinomycin. Increased incidence of gastrointestinal toxicity and bone marrow suppression has been reported when Dactinomycin was given with x-ray therapy.
Storage
Store at temperatures between 8°C-15°C. Refrigerate, do not freeze.
ATC Classification
L01DA01 - dactinomycin ; Belongs to the class of cytotoxic antibiotics, actinomycines. Used in the treatment of cancer.
Presentation/Packing
Inj (vial) 500 mcg (yellow to light red, crystalline powder) x 1's.
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