Aknomid D

General characteristics. Structure:

Active ingredient: 0,5 mg of Dactinomycinum.

Excipients: реополиглюкин, solution for infusions (10% dextran solution, with a molecular weight from 3000 to 4000, in isotonic solution of sodium of chloride).

Antineoplastic drug.

Pharmacological properties:

Pharmacodynamics. Pharmacological action of Dactinomycinum preferential antineoplastic, however, besides, drug has antibacterial, antifungal effect.

Formation of a complex about DNA and disturbance of its matrix activity is the cornerstone of the mechanism of antineoplastic effect of drug. At the same time Dactinomycinum is interkalirut between base pairs by DNA guanine-tsitozin and obstructs the traffic of a RNA polymerase, breaking, thus, a transcription. There are data on the inhibiting influence on topoisomerase II. The antineoplastic effect does not depend on a phase of a cellular cycle.

Drug has antibacterial effect concerning gram-positive and gram-negative bacteria and antifungal action, however, owing to high toxicity (LD 50 - 0.791) as antimicrobic means is not applied. Besides, Dactinomycinum has immunodepressive activity.

Pharmacokinetics. At intravenous administration drug collects in nuclear cells, in insignificant degree gets through a blood-brain barrier (<10%); gets through a placenta. Substantially contacts proteins of fabrics. It is metabolized poorly. The elimination half-life makes 36 h. It is removed with bile – 50% in not changed look, kidneys – 10% in not changed look. At bolyusny intravenous infusions of Dactinomycinum at adults in doses from 0,7 to 1,5 mg/m ² - the maximum concentration of drug in number of 25,1 ng/ml is noted in 15 minutes after introduction. The average size of concentration of Dactinomycinum in 6 hours makes 2,67 mg/l.....

Indications to use:

- Nefroblastoma (Vilms's Tumour);

- Rhabdomyosarcoma;

- Ewing's sarcoma;

- Neseminomny malignant tumors of a small egg;

- Trophoblastic tumors;

- Local and recurrent or locally-spread solid tumors;

- In combination with radiotheraphy;

- In the preoperative and postoperative periods.

Route of administration and doses:

Intravenously. Intravenous infusional administration of drug Aknomid Д® has to be carried out only in the conditions of a hospital.

The drug dose Aknomid Д® is selected individually, depending on portability of drug the patient, and also from the chosen program of antineoplastic therapy. The daily dose both for adults, and for children should not exceed 15 mkg/kg or 400-600 mkg/m ² during 5-7dny. Usually the dose for adults makes 500 mkg a day in/in a maximum within 5-7 days.

When calculating a dose at patients with obesity or hypostases it is necessary to consider the body surface area that the dose corresponded to Sukhoi body weight. To children appoint 15 mkg/kg in days in/in within 5 days. There is an alternative course - the general dose of 2500 mkg/m ² in/in in a week. Both for adults, and for children, the repeated course of treatment can be carried out by drug not earlier than in 3 weeks (on condition of disappearance of all signs of toxic effects).

At a nefroblastoma (Vilms's tumor) the recommended dose makes 15 mkg/kg a day within 5 days intravenously in combination with other chemotherapeutic means in various schemes of treatment, also drug is appointed in a dose of 45 mkg/kg intravenously at Vilms's tumor; in a dose of 1.25 mg/sq.m intravenously struyno within 3-5 minutes in the first day each 42 days drug is appointed at Ewing's sarcoma; at neseminomny malignant tumors of an ovary the recommended dose makes 1000 mkg/sq.m intravenously in the first day of treatment in combination with cyclophosphamide, bleomycin, vinblastine and Cisplatinum; at trophoblastic tumors the recommended dose makes 12 mkg/kg a day within 5 days as monotherapy and in a dose of 500 mkg intravenously in 1,2 days as a component of the combined mode with etopozidy, a methotrexate, calcium folinaty, Vincristinum, cyclophosphamide and Cisplatinum. Use of a combination therapy Dactinomycinum and Vincristinum together with surgical treatment and radiotheraphy is possible, at the same time Dactinomycinum and Vincristinum apply during 7 cycles, thus, duration of a maintenance therapy makes about 15 months.

At a rhabdomyosarcoma use the following combinations: Vincristinum and Dactinomycinum; Vincristinum, Dactinomycinum and cyclophosphamide (VAC - therapy), and also all four drugs consistently.

At local and recurrent or locally-spread solid tumors in combination with radiotheraphy, the usual course dose of Dactinomycinum for adults makes 500 mkg a day in/in a maximum within 5-7 days, for children - 15 mkg/kg or 400 mkg/m ² / days respectively.

- the drug Aknomid Д® is administered intravenously in the form of 0,05% of solution of a reopoliglyukin. It can be added to infusion solutions: 5% solution of a dextrose or – 0,9% chloride sodium solution

- drug Aknomid Д® can also be used by method of the isolated perfusion. Advantage of a method is the minimum hit of drug to other regions through a system blood stream and the prolonged impact on a tumor.

The dose of drug can be significantly higher than the dose used at a system way of introduction, at the same time danger of emergence of toxic effects usually is less.

Average doses: 50 mkg/kg for the lower extremities and bodies of a basin;
35 mkg/kg for upper extremities. To patients with obesity, and also in cases of preliminary treatment chemotherapeutic drugs and radiation recommend to appoint smaller doses of drug.

Features of use:

Drug Aknomid Д® has to be used only under careful observation of the doctor having experience of use of antineoplastic chemotherapeutic drugs; the symptoms of nausea and vomiting developing within the first hours after administration of medicine can be stopped antiemetic medicines; distorts results of the bioasseys used for definition of efficiency of antibacterial medicines; when performing joint radiation therapy the risk of development of toxic reactions from digestive tract increases and oppression of marrow; with extra care drug is appointed during two-month therapy of a right-hand tumor of Vilms, at the same time the hepatomegalia and increase in activity of "hepatic" transaminases are noted; strengthens action of radiation therapy. Solution preparation, owing to high toxicity, is recommended to be carried out in a case with biological protection of a class 2 with a laminar flow; the personnel which are carrying out its preparation have to put on surgical gloves and closed (surgical type) a dressing gown with the tied cuffs.

At accidental hit of drug in eyes it is necessary to wash out immediately a large amount of water, and then to address for consultation the ophthalmologist; at hit on skin it is necessary to wash out the contaminated surface a large amount of water within 15 minutes.

At development of the expressed miyelosupressiya therapy by drug Aknomid Д®, especially when it is applied in a combination with other antineoplastic drugs, has to be stopped before recovery of function of marrow, usually it takes about three weeks.

Complications after use of a technique of perfusion are generally connected with amount of the medicine which came to a system blood stream and can be characterized by oppression of the hemopoietic function, absorption of toxic decomposition products from the site of massive destruction of the tumoral fabric raised by a susceptibility to infections, deterioration in healing of wounds and a superficial ulceration mucous a stomach; other undesirable effects can include hypostasis of the involved extremity, damage of soft tissues to a zone of perfusion and (perhaps) venous fibrinferments; there are messages testimonial of increase of cases of emergence of secondary malignant new growths, including leukemia, after use of the schemes of treatment including Dactinomycinum irrespective of co-administration of radiation therapy; women and men during treatment and within 3 months after the end of therapy by drug Aknomid Д® should use reliable ways of contraception.

In the course of treatment Aknomid Д® it is necessary to carry out by drug daily determination of content of thrombocytes and leukocytes. At essential reduction of quantity of thrombocytes or leukocytes it is necessary to stop administration of drug before recovery of function of marrow (usually it takes about 3 weeks).

Also systematic definition of activity of "hepatic" enzymes, bilirubin, carrying out the general analysis of urine is shown.

The nausea and vomiting caused by drug use Aknomid Д® result in need of purpose of drug discontinuous courses.

At hit of drug under skin and in fabric it is necessary to interrupt infusion, but to leave a needle on site. To try to extract the streamed drug through a needle; if necessary to enter an antidote (1,6 ml of 25% of solution of sodium thiosulphate from 3 ml of water for injections; or 4 ml of 10% of solution of sodium thiosulphate from 6 ml of water for injections + 1 ml/50 mg / ascorbic acid). After introduction of an antidote the needle should be removed. The extremity should give sublime situation and to impose a cold compress for 45 min.

Unused drug should be thrown out, having preposted neutralization of 5% trisodiums phosphate within 30 min.

Influence on ability to manage vehicles and mechanisms. As drug Aknomid Д® is capable to exert impact on the central nervous system (feeling of fatigue, dizziness), - during treatment it is necessary to abstain from driving of vehicles and from occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Toxic reactions to Dactinomycinum are frequent and can be heavy. Excepting nausea and vomiting, they usually are not found before 2-4 days after the termination of a course of therapy and can not be most expressed within 1-2 weeks.

General frustration: indisposition, increased fatigue, slackness, drowsiness, fever, muscular pains, hypocalcemia.

Disturbances from system of blood and lymphatic system: anemia (up to aplastic anemia), an agranulocytosis, a leukopenia, thrombocytopenia, a pancytopenia, a reticulocytopenia.

Gastrointestinal frustration: cheilitis, esophagitis, stomacace, pharyngitis, anorexia, nausea, vomiting, dysphagy, abdominal pains, diarrhea, gastrointestinal ulcers, proctitis.

Frustration of gepatobiliarny system: toxic damage of a liver (with possible development of hepatitis), jaundice, a cholestasia, increase in level of liver enzymes (most often associated with a cholestasia), a liver failure.

Changes from skin and hypodermic cellulose: an alopecia, rash, an acne, a recurrence of an erythema or strengthening of pigmentation of sites of skin which were exposed to radiation earlier; Stephens's syndrome — Johnson, a toxic epidermal necrolysis, a mnogoformny erythema. There are messages on an epidermolysis, an erythema and hypostasis, sometimes, enough expressed, arisen at partial perfusion of an extremity.

Disturbances from respiratory system, bodies of a thorax and a mediastinum: a pneumonitis, an intersticial disease of lungs, especially at long-term treatment.

Vascular frustration: primary thrombosis of hepatic veins obliterating an endophlebitis of hepatic veins.

Disbolism, metabolism, growth inhibition.

Disturbances from immune system: the increased risk of development of secondary infectious diseases, sepsis (including neytropenichesky sepsis).

Interaction with other medicines:

Other antineoplastic drugs and radiation therapy exponentiate effect of Dactinomycinum.

At simultaneous use of Dactinomycinum with the drugs having myelotoxic effect strengthening of toxic effect is possible.

At simultaneous use of Dactinomycinum with uricosuric means the risk of emergence of a nephropathy increases.

At the combined use with doxorubicine strengthening of cardiotoxic action is possible.

Dactinomycinum weakens an immune response on introduction of the inactivated virus vaccines; against the background of therapy with use of this drug it is necessary to refrain from vaccination by live virus vaccines.

Besides, use of Dactinomycinum weakens effect of vitamin K.

Contraindications:

- individual intolerance (including hypersensitivity in the anamnesis) Dactinomycinum or components of drug Aknomid Д®;

- chicken pox, the shingles (surrounding herpes, Herpes zoster): the serious generalized illness which can end with death can develop;

- oppression of function of marrow, the expressed tsitopenichesky reaction at medicinal or radiation therapy (in the anamnesis);

- the expressed abnormal liver functions, a liver failure;

- hyperuricemia;

- pregnancy, breastfeeding;

- children's age up to 6 months.

With care: at patients 65 years (the increased risk of a miyelosupressiya) are more senior; at gout or renal concrements (an uratny nephrolithiasis) in the anamnesis (risk of a hyperuricemia); at the previous cytotoxic or radiation therapy; after carrying out chemotherapy or radiation therapy, a concomitant use with live virus vaccines.

Overdose:

Symptoms are: nausea, vomiting, diarrhea, stomatitis, GIT ulcers, the expressed oppression of a hemogenesis, an acute renal failure, the lethal outcome is possible.

Treatment: symptomatic and supporting. Frequent control of function of kidneys, a liver and marrow is recommended.

Storage conditions:

To store at a temperature not above 10 °C. To store in the place, unavailable to children. A period of validity - 3 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Solution for intravenous administration and perfusion of 0,5 mg/ml, on 1 ml of solution in ampoules of dark glass, on 5 ampoules in a plastic case, on 1 case together with the instruction on a medical use in a cardboard pack.