Alkeran pills 2 mg №25

Active ingredient and dosage form

Alkeran coated tablets:
1 tab. contains melphalan hydrochloride 2 mg
Excipients: MCC; crospovidone; colloidal silicon dioxide; Magnesium stearate; opadry white (hypromellose, titanium dioxide, macrogol);
in dark glass bottles 25 pcs.; in the box 1 bottle.

Mechanism of action

Antitumor (cytostatic).

Covalently binds (alkylates) carbon intermediates formed from two bis-2-chloroethyl groups with 7-nitrogen guanine in DNA. Due to the formation of cross-links in the DNA molecule causes a violation of cell division, leading to their death.

Indications and usage

Multiple myeloma, ovarian adenocarcinoma, breast carcinoma, polycythemia vera, localized malignant melanoma and soft tissue sarcoma of the extremities, neuroblastoma (in children).

Contraindications

Pregnancy. Alkeran is not recommended for use in the first trimester of pregnancy. When applied in the II and III trimesters, the expected benefit for the mother should be correlated with the potential risk to the fetus. If necessary, the appointment of the drug during lactation should decide on the termination of breastfeeding.
As with the use of any cytotoxic drugs, when treating children of childbearing age with Alkeran, reliable methods of contraception should be used.
The possible teratogenic effect of Alkeran has not been studied. Due to the mutagenic properties of the drug and its structural similarity with known teratogenic substances, it is suggested that melphalan can cause birth defects in children born to patients who have been treated with this drug.

Dosage and administration

It is used as an alternative to surgical treatment in the early stages of the process and as a palliative treatment for advanced but localized forms of cancer.
Multiple myeloma: by mouth, 0.15 mg / kg / day in divided doses for 4 days, the interval between courses is 6 weeks; w / w - from 8 mg / m ^ 2 to 30 mg / m ^ 2 with intervals of 4-6 weeks (when combined with cytotoxic drugs) or 0.4 mg / kg (16 mg / m ^ 2) once every 4 weeks with monotherapy, or once in / with the introduction of from 100 to 200 mg / m ^ 2 (2.5-5.0 mg / kg).
Ovarian adenocarcinoma: inside - 0.2 mg / kg / day for 5 days, the course is repeated every 4-8 weeks. In / in, with monotherapy - 1 mg / kg (40 mg / m ^ 2) at intervals of 4 weeks. When combined with cytostatics - 0.3-0.4 mg / kg (12-16 mg / m ^ 2) at intervals of 4-6 weeks.
Breast carcinoma: inside - 0.15 mg / kg / day or 6 mg / m ^ 2 for 5 days at intervals of 6 weeks.
Polycythemia true: 6-10 mg / day for 5-7 days (induction of remission), then 2-4 mg / day. Maintenance therapy - 2-6 mg once a week.
Neuroblastoma in children: 100-240 mg / m ^ 2 (sometimes within 3 days).
Malignant melanoma and soft tissue sarcoma: hyperthermic regional perfusion.

Adverse reactions

Myelodepression (leukopenia, thrombocytopenia, anemia), dyspepsia (nausea, vomiting, diarrhea), stomatitis, allergic rash, itching, baldness, hyperuricemia; rarely: pneumofibrosis, hemolytic anemia, in women (during menopause) - suppression of ovarian function.

Overdosage

Symptoms: nausea, vomiting, diarrhea (sometimes hemorrhagic type). The main toxic effect of melphalan is to suppress the function of the bone marrow with the development of leukopenia, thrombocytopenia and anemia.
Treatment: If necessary, conduct general supportive therapy in conjunction with the transfusion of blood components and platelet mass; the issue of hospitalization of the patient, the appointment of antibiotic therapy and the use of hematopoietic growth factors should be resolved. There is no specific antidote. It is necessary to carefully monitor hematological parameters for at least 4 weeks until signs of their normalization are noted.

Special notes

Alkeran is a cytotoxic agent and is intended for use only under the supervision of physicians with experience in the use of such drugs.
Considering the well-known risk arising from drug treatment and the need for adjuvant therapy, the use of Alkeran solution in high doses should be carried out in specialized centers with appropriate conditions, and only by experienced specialists.In patients receiving high doses of Alkeran, it is necessary to resolve the issue of the prophylactic administration of antibacterial agents, the use of blood components if necessary, and the maintenance of abundant diuresis immediately after the administration of Alkeran (by using hydration and forced diuresis).
Before the introduction of high doses of Alkeran should ensure the adequacy of the general condition of the patient and the function of internal organs. When using Alkeran, the recommendations on the use of cytotoxic drugs should be followed.
The solution of Alkeran in the case of contact with the tissue surrounding the vessel can lead to local tissue damage.
Alkeran should be used with caution in patients who have recently undergone radiation therapy or Chemotherapy, in connection with the possibility of increasing the toxic effect on the bone marrow.
In patients with renal insufficiency, blood formation can be suppressed in the presence of uremia.
In patients with myeloma and impaired renal function in the early stages of treatment with melphalan, a temporary marked increase in the blood urea level was observed.
Melphalan inhibits ovarian function in premenopausal women, leading to amenorrhea in a significant number of patients. According to animal studies, melphalan may have an adverse effect on spermatogenesis. Therefore, it is assumed that melphalan can cause temporary or permanent sterility in male patients.
In patients treated with melphalan, chromosomal aberrations were noted.
Melphalan, like other alkylating agents, can have a leukemic effect in humans. There are reports of the development of acute leukemia after long-term treatment of such diseases as amyloidosis, malignant melanoma, multiple myeloma, macroglobulinemia, cold hemagglutination syndrome and ovarian cancer with melphalan. In patients with ovarian cancer, it has been shown that the use of alkylating agents, including melphalan, significantly increased the incidence of acute leukemia compared with patients who were not treated with alkylating agents. When deciding on the appointment of melphalan, one should compare the risk of a leuke-carrying effect and the potential therapeutic effect of the drug.
Control of laboratory parameters
It is necessary to regularly monitor hematological parameters in order to avoid the possible development of severe myelosuppression and the risk of irreversible aplasia of the bone marrow. The number of blood cells may continue to decrease even after drug withdrawal, therefore, at the first signs of an excessive decrease in the number of white blood cells or platelets, treatment should be temporarily stopped.
Use in pediatrics
Alkeran's solution for injection in high doses under the protection of autologous bone marrow is used in children with neuroblastoma.
Alkeran in standard doses is indicated for children only in rare cases, therefore data on recommended doses cannot be given.
Influence on ability to drive motor transport and control mechanisms
There is no data on the effect of Alkeran on the ability to engage in potentially hazardous activities requiring increased attention.

Drug Interactions

Increases the likelihood of impaired renal function in patients with bone marrow transplants receiving cyclosporine for the prevention of graft versus host disease. Concurrent use with nalidixic acid and cyclosporin should be avoided. In children, it is incompatible (w / w) with nalidixic acid - death is possible as a result of hemorrhagic enterocolitis.

Caution is prescribed to patients who have recently undergone radiotherapy and chemotherapy, with impaired renal function. Nursing mothers should stop breastfeeding. The treatment is carried out under the control of a picture of peripheral blood and should be temporarily stopped if there is a threat of excessive myelosuppression and irreversible aplasia of the bone marrow. As a rule, after it is canceled, the number of leukocytes and platelets continues to decrease for a while. In patients with severe and moderately impaired renal function, the initial dose for intravenous administration should be reduced by 50%, subsequent doses are determined based on the response of peripheral blood.In connection with the variable absorption after oral administration, the dosage must be increased carefully, before the onset of myelosuppression, which will indicate the achievement of potential therapeutic concentrations.

: List A. In the dark place at a temperature of 2-8 ° C

2 years.