Expiration date: 01/2025
Composition and form of issue:
Tablets, film-coated. 1 tablet contains:
melphalan 2 mg
other ingredients: microcrystalline crospovidone silicon dioxide colloidal magnesium stearate Opadry white (hypromellose, titanium dioxide, macrogol)
in the bottle dark glasses to 25 PCs. in carton of 1 vial.
Powder lyophilized for the preparation of solution for injection. 1 flask comtains:
melphalan hydrochloride 50 mg
excipients: povidone K12 hydrochloric acid
in a bottle of 10 ml complete with solvent (in a bottle of 10 ml) or in a bottle of 10 ml in a plastic case 1 bottle.
Pharmacokinetics:
In applying the drug inside the initial appearance of melphalan in plasma varies from 0 to 336 min Cmax ranges from 70 to 630 ng/ml. Final T1/2 of plasma — 90±57 min for 24 h in the urine detected 11% of the dose.
After a single, bolus, the introduction of Alkeran in doses of 0, 5-0, 6 mg/kg, combined initial and final T1/2 were, respectively, 7, 7±3, 3 min and 108±20, 8 min. After injection, plasma was detected monohydroxylation and dihydroxymorphinan their concentration reached a maximum after approximately 60 and 105 min, respectively.
Description of pharmacological action:
Covalent binding (alkiliruet) carbon intermediate compounds formed from two bis?2-chloroethyl groups, with 7-nitrogen guanine in DNA. Due to the formation of cross-linking in the DNA molecule causes a violation of cell division, leading to their death.
Indications:
Multiple myeloma, ovarian adenocarcinoma, breast carcinoma, true polycythemia, localized malignant melanoma and soft tissue sarcoma of the limbs, neuroblastoma (in children).
Contraindications:
Pregnancy.
Side effect:
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.
Drug interaction:
Increases the likelihood of renal dysfunction in bone marrow transplant patients receiving cyclosporine to prevent graft-versus-host disease. It is necessary to avoid simultaneous use with nalidixic acid and cyclosporine. Children inconsistent (V/V) of nalidixic acid may be fatal as a result of haemorrhagic enterocolitis.
Dosage and administration:
Dosage and administration. Inside, in/ in, in / a. Alkeran should be prescribed only by doctors who have experience in the treatment of malignant tumors with cytotoxic drugs. When taking the tablet should not be divided into parts. Absorption of melphalan after oral administration is variable. If necessary, the dose can be gradually increased until signs of myelosuppression in order to provide therapeutic concentrations of the drug. The solution of Alkeran for injection is administered in intermittent mode, as in monotherapy, and in combination with other cytotoxic agents. In some schemes of treatment in addition prednisone. More detailed treatment regimens are given in the literature.
Multiple myeloma: inside-0, 15 mg/kg/day in several doses for 4 days, the interval between courses — 6 weeks/in — from 8 to 30 mg/m2 with breaks 2-6 weeks (when combined with cytostatics) or 0, 4 mg/kg (16 mg / m2) 1 time in 4 weeks with monotherapy (repeated administration is made subject to recovery during this period of peripheral blood). High-dose therapy-a single I/V administration of 100 to 200 mg/m2 (2, 5-5, 0 mg / kg). After the use of the drug in doses exceeding 140 mg/m2, autologous bone marrow transplantation is necessary. In case of renal insufficiency, the dose should be reduced by 50%.
Ovarian adenocarcinoma: inside-0, 2 mg/kg / day for 5 days, the course is repeated every 4-8 weeks or as bone marrow function is restored. In / in, with monotherapy-1 mg/kg (about 40 mg / m2) at intervals of 4 weeks. When combined with cytostatics-0, 3-0, 4 mg/kg (12-16 mg / m2) at intervals of 4-6 weeks.
True polycythemia: inside-6-10 mg/day for 5-7 days (induction of remission), then — 2-4 mg / day. Maintenance therapy-2-6 mg once a week.
Progressive neuroblastoma in children: in/in — 100-240 mg / m2 (sometimes the dose is administered in 3 doses for 3 days) both in monotherapy and in combination with radiation therapy and/or other cytostatics, under the protection of autologous bone marrow.
Malignant melanoma: b / a, hyperthermal regional perfusion of Alkeran solution is used as adjuvant therapy of malignant melanoma at an early stage of the disease, as well as palliative treatment at later stages in a localized form. Detailed information on perfusion techniques and recommended doses can be found in the literature.
Soft tissue sarcoma: b/a, hyperthermal regional perfusion of Alkeran solution is used in localized form, usually in combination with surgical treatment, at all stages of the disease. It is also possible to use in combination with actinomycin D. Detailed information on the technique of perfusion and the recommended doses are given in the literature.
Application in children: alkeran solution in high doses under the protection of autologous bone marrow is used in children with neuroblastoma. The drug in standard doses is shown only in rare cases, so the data on the recommended doses can not be given.
Use in the elderly: before using the drug in high doses should ensure the adequacy of the General condition and functions of the internal organs.
Use in renal insufficiency: if the solution of Alkeran for injection is used in standard doses (8-40 mg / m2), in patients with moderate and severe renal insufficiency, it is recommended to reduce the initial dose by 50%, and subsequently select it depending on the degree of inhibition of bone marrow function. In high-dose therapy (100-240 mg / m2), the need to reduce the dose depends on the degree of renal dysfunction, medical purposes and whether the infusion of autologous bone marrow stem cells is carried out. As a rule, with moderate and severe renal failure (CL creatinine — 30-50 ml/min), the dose is reduced by 50%. It is also necessary to introduce a sufficient amount of liquid and conduct forced diuresis. Patients with more severe renal failure (Cl creatinine < 30 ml/min) to appoint a high dose of Alkeran is not recommended.
Rules of preparation of the solution of Alkeran for injection
The solution is prepared at room temperature immediately before use (has limited stability) by mixing the lyophilized powder with a solvent, which is attached to the bottle with Alkane. In a bottle with lyophilized powder should be added 10 ml of solvent (simultaneously) and vigorously shaken until completely dissolved. The resulting solution contains 5 mg of anhydrous melphalan in 1 ml and has a pH of about 6, 5. The prepared solution can not be stored in the refrigerator, because it causes the formation of sediment.
Rules of introduction of the solution of Alkeran for injection
The solution used for on/in the introduction, with the exception of cases when it is shown holding regional arterial perfusion. At/in the application of the solution of Alkeran advised to enter slowly with the rapid infusion of a different solution.. It is recommended to dilute only 0, 9% solution of sodium chloride for injection, it should not be mixed with solutions containing dextrose. The stability of the solution of Alkeran for injection is reduced by its further dilution in infusion solution and also with increasing ambient temperature. At room temperature (approximately 25 °C), the total time from the moment of preparation of the solution of Alkeran for injection to the completion of its infusion should not exceed 1, 5 hours.If in the prepared or diluted solution of Alkeran appears turbidity or crystallization, it should be destroyed. When administered, extravasation should be avoided. In case of difficult access to peripheral veins, the drug is injected into the Central veins. High doses of Alkeran advised to enter a Central vein. When using the drug for regional arterial perfusion is recommended to read the details of the technique in the literature.
Precautionary measures:
With caution is prescribed to patients who have recently undergone radiation and chemotherapy, with impaired renal function. Nursing mothers should stop breast-feeding. Treatment is carried out under the control of the peripheral blood picture and should be temporarily discontinued with the threat of excessive myelosuppression and irreversible bone marrow aplasia. As a rule, after its abolition, the number of leukocytes and platelets continues to decrease for some time. In patients with severe and moderate renal impairment, the initial dose for I / V administration should be reduced by 50%, subsequent doses are determined based on the reaction of peripheral blood. Due to variable absorption after oral administration, the dosage should be increased carefully, before the onset of myelosuppression, which will indicate the achievement of potential therapeutic concentrations.
