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medicalmeds.eu Medicines Antineoplastic drug. Alkeran

Alkeran

Препарат Алкеран. Glaxo Operetaions UK Limited (Глаксо Оперейшнс ЮК Лимитед) Великобритания


Producer: Glaxo Operetaions UK Limited (Glakso Opereyshns YuK Limited) Great Britain

Code of automatic telephone exchange: L01AA03

Release form: Firm dosage forms. Tablets.

Indications to use: Melanoma. Sarcoma of soft tissues. Ovarian cancer. Multiple myeloma. Neuroblastoma. Polycythemia. Breast cancer.


General characteristics. Structure:

Active ingredient: Melphalanum of 2 mg

Excipients: cellulose microcrystallic, кросповидон, silicon dioxide colloid, magnesium stearate.

Structure of a cover: Опадрай white YS-1-18097-A (gipromelloza, titanium dioxide, macrogoal).

25 - bottles of dark glass (1) - a pack cardboard.

The lyophilized powder for preparation of solution for injections of white or almost white color; the enclosed solvent transparent, colourless solution with a spirit smell; at dissolution in 10 ml of solvent practically does not contain visible particles.

 1 фл.
Active ingredient: Melphalanum (in the form of a hydrochloride) 50 mg

Excipients: K12 povidone, Acidum hydrochloricum.

Solvent: sodium citrate, propylene glycol, ethanol, water for and.

Bottles glass (1) complete with solvent (10 ml - фл.) - cases plastic (1) - packs cardboard.




Pharmacological properties:

Antineoplastic drug, the bifunctional alkylating connection. Process of alkylation consists in covalent binding formed of two encore - 2-chlorethyl groups of carbon intermediate compounds with 7 nitrogen of guanine in DNA and cross binding of two chains of DNA that leads to disturbance of replication of cells.

In/in Alkeran's introduction in the form of monotherapy or in a combination with other cytotoxic drugs also effectively at a multiple myeloma, as well as oral administration of Alkeran. In/in Alkeran's introduction in high doses (with transplantation of haematopoietic stem cells or without it) as the first line of therapy or for consolidation of remission after standard cytostatic chemotherapy leads to full remission at 50% of patients with a multiple myeloma.

Alkeran in high doses (with transplantation of stem hemopoietic cells or without it) was applied both in the form of monotherapy, and in a combination with radiation therapy and/or other cytotoxic drugs, to consolidation of remission after standard treatment at a widespread neuroblastoma at children.

In/in Alkeran's introduction in the form of monotherapy and in a combination with other cytotoxic drugs allows to reach objective effect approximately at 50% of patients with a widespread adenocarcinoma of an ovary.

Administration of drug in the form of monotherapy or in a combination with other drugs renders considerable therapeutic effect at a number of patients with a widespread carcinoma of a mammary gland; besides, Melphalanum was applied within adjuvant therapy after operation for a carcinoma of a mammary gland.

It is effective at treatment of patients with an Osler's disease.

Pharmacokinetics. Absorption

At 13 patients receiving Melphalanum orally in a dose of 0.6 mg/kg of body weight, absorption was characterized by big variability – as on time before the first emergence of drug in plasma (range from 0 to 336 min.), and on Cmax value in plasma (range from 70 to 63 ng/ml). At 5 patients to whom the equivalent dose of Melphalanum was entered in/in average absolute bioavailability made there were 56±27%.

Melphalanum pharmacokinetics at in introduction in standard and high doses corresponds to bi-exponential two-chamber model.

. At 18 patients receiving Melphalanum orally in doses from 0.2 to 0.25 mg/kg of body weight, Cmax in plasma (range from 87 to 350 ng/ml) it was reached within 0.5–2.0 h. At reception of tablets of Melphalanum at once after food time in plasma increased to achievement of Cmax, and AUC decreased by 39 – 45%.

Distribution

After administration of drug in the form of two-minute infusion in doses from 5 to 23 mg/sq.m of a body surface (about 0.1 - 0.6 mg/kg of body weight) to 10 patients with cancer of an ovary or a multiple myeloma average Vd in an equilibrium state and the central kompartment was made by 29.1±13.6 l and 12.2±6.5 l respectively. At 28 patients with various malignant new growths receiving drug in doses from 70 to 200 mg/sq.m of a body surface in the form of 2-20-minute infusions, average Vd in an equilibrium state and the central kompartment respectively 40.2±18.3 l and 18.2±11.7 l equaled.

At hyper thermal (39 °C) perfusions of the lower extremity Melphalanum in a dose of 1.75 mg/kg of body weight at 11 patients with a widespread melanoma average Vdv an equilibrium state and the central kompartment equaled respectively 2.87±0.8 l and 1.01±0.28 l.

Metabolism

The data obtained by in vivo and in vitro allow to assume that the main factor defining drug T1/2 at the person is spontaneous degradation, but not fermental.

Removal

At 13 patients after oral administration of Melphalanum in a dose of 0.6 mg/kg of body weight average T1/2 of a final phase equaled 90±57 min., at the same time for 24 h in urine 11% of drug were found.

At 8 patients after single bolyusny introduction of Alkeran in a dose of 0.5-0.6 mg/kg of T1/2 in an initial and terminal phase made respectively 7.7±3.3 and 108±20.8 min. After parenteral administration of Melphalanum in plasma its metabolites - monohydroxymelphalanum and dihydroxymelphalanum which concentration reached the maximum levels for 60 and 105 min. according to were defined. T1/2 at addition of Melphalanum to serum of patients of in vitro at 37 °C was similar to that in vivo and made 126±6 min. It allows to assume that the main factor determining duration of T1/2 in a human body is more likely its spontaneous degradation, but not fermental metabolism.

After administration of drug in the form of two-minute infusion in doses from 5 to 23 mg/sq.m of a body surface (about 0.1-0.6 mg/kg of body weight) to 10 patients with cancer of an ovary or a multiple myeloma of T1/2 in an initial and terminal phase made respectively 8.1±6.6 and 76.9±40.7 minutes, and average clearance – 342.7±96.8 ml/min.

At 15 children and 11 adults receiving high-dose (140 mg/sq.m of a body surface) in/in therapy by Melphalanum against the background of an artificial diuresis, average T1/2 in an initial and terminal phase was made by respectively 6.5±3.6 and 41.4±16.5 min. At 28 patients with various malignant new growths receiving drug in doses from 70 to 200 mg/sq.m of a body surface in the form of 2-20-min. infusions average T1/2 in an initial and terminal phase made respectively 8.8±.6 and 73.1±45.9 min., and average clearance – 564.6±159.1 ml/min.

At hyper thermal (39 ° C) perfusions of the lower extremity Melphalanum in a dose of 1.75 mg/kg of body weight at 11 patients with a widespread melanoma average T1/2 in an initial and terminal phase made respectively 3.6±1.5 and 465±17.2 min. according to, and average clearance – 55.0±9.4 ml/min.

At 18 patients receiving Melphalanum orally in a dose of 0.2-0.25 mg/kg of body weight, average T1/2 left 1.12±0.15 h.


Indications to use:

For parenteral use

Partial arterial perfusion is shown at:

— to the localized melanoma of extremities;

— to the localized sarcoma of soft tissues of extremities.

In/in introduction in standard doses it is applied at:

— to a multiple myeloma;

— widespread cancer of an ovary

In/in introduction in high doses it is applied to treatment:

multiple myeloma;

— a widespread neuroblastoma at children.

For intake

It is shown at:

— to a multiple myeloma;

— to a widespread adenocarcinoma of an ovary.

It can be applied at:

— to a carcinoma of a mammary gland;

— Osler's disease.


Route of administration and doses:

Alkeran has to be appointed only the doctors having experience of performing cytostatic therapy of malignant new growths.

The adult at a multiple myeloma for parenteral administration Alkeran's solution for injections is appointed in the intermittent mode both in the form of monotherapy, and in a combination with other cytotoxic means, in the range of doses from 8 to 30 mg/sq.m of a body surface, bucketed from 2 to 6 weeks. Some schemes of treatment in addition join Prednisolonum. More detailed schemes of treatment are provided in special literature. At in/in monotherapy the usual mode of dosing of Alkeran makes 0.4 mg/kg of body weight (16 mg/sq.m) with repeated introduction with the corresponding intervals (for example once each 4 weeks) on condition of recovery for this period of indicators of peripheral blood. At use in the mode of high-dose therapy Alkeran enter once in/in in a dose from 100 to 200 mg/sq.m (from about 2.5 to 5.0 mg/kg of body weight). At use of drug in doses more than 140 mg/sq.m of a body surface are very important to carry out transplantation of haematopoietic stem cells. At a renal failure the dose of drug should be reduced on 50. Taking into account the expressed myelosuppressive action at in high doses this therapy has to be carried out to therapies only in the specialized centers under observation of experienced specialists.

The adult at a multiple myeloma for intake usually appoint 0:15 mg/kg of body weight in stages for 4 days, repeating the bucketed cycles of 6 weeks. However also many other modes with which it is possible to get acquainted in detail in special literature were used. Reception of Melphalanum inside with co-administration of Prednisolonum can be more effective, than monotherapy by Melphalanum. The combination therapy is usually appointed according to the discontinuous scheme.

Therapy lasting more than 1 year at the patients answering therapy, apparently, is not followed by higher performance.

At a widespread adenocarcinoma of ovaries at in introduction in the monotherapy mode Alkeran are usually applied in a dose of 1 mg/kg of body weight (about 40 mg/sq.m) at an interval of 4 weeks. At use in a combination with other cytotoxic means the recommended Alkeran's doses makes from 0.3 to 0.4 mg/kg of body weight (from 12 to 16 mg/sq.m) at an interval of 4–6 weeks. At intake usually appoint 0.2 mg/kg of body weight a day for 5 days, repeating the cycles each 4 – 8 weeks or after recovery of a picture of peripheral blood.

At a melanoma hyper thermal partial perfusion is applied by Alkeran's solution as adjuvant therapy after removal of a melanoma at an early stage of a disease, and also as palliative treatment of a locally-spread stage. Detailed information on technology of perfusion and on the recommended doses is provided in special literature.

At sarcoma of soft tissues hyper thermal partial perfusion of solution of Alkeran is applied at all stages of the localized sarcoma of soft tissues, usually in a combination with surgical treatment. Alkeran is also appointed in combination with Actinomycinum of D. Detailed information on the recommended doses is provided in special literature.

At a carcinoma of a mammary gland Alkeran appoint inside in a dose 0.15 mg/kg of body weight or 6 mg/sq.m of a body surface a day for 5 days, repeating the cycles each 6 weeks. At toxic action on a marrowy hemopoiesis the dose is reduced.

At an Osler's disease for remission induction drug is appointed inside in doses from 6 to 10 mg a day within 5-7 days then pass to reception in a dose from 2 to 4 mg a day before achievement of sufficient control of a disease. For a maintenance therapy drug appoint in a dose from 2 to 6 mg once a week

Considering a possibility of a heavy miyelosupressiya at continuous reception of Melphalanum, it is regularly very important to investigate throughout all therapy a blood picture, if necessary adjusting a dose or doing breaks in treatment for maintenance of good control of a picture of blood.

At a widespread neuroblastoma at children Alkeran's solution for injections appoint in doses from 100 to 240 mg/sq.m (sometimes this dose is divided into several equal parts and enter within three days in a row) both in the monotherapy mode, and in a combination with radiation therapy and/or with other cytotoxic means, in combination with transplantation of haematopoietic stem cells.

Melphalanum in the traditional range of doses is appointed to children only in rare instances therefore it is not possible to make accurately certain recommendations about dosing.

Alkeran is often applied at patients of advanced and senile age in standard doses, there is no information on features of its use in this age subgroup.

Experience of use of Alkeran in high doses for patients of advanced and senile age is limited. Before high-dose in/in therapy by Melphalanum it is necessary to achieve an adequate general state from patients of this category.

At a renal failure the clearance of Melphalanum can decrease though strongly varies. At in administration of drug in standard doses (8–40 mg/sq.m) patients with a moderate or heavy renal failure are recommended to reduce an initial dose by 50%, and further to select a dose depending on extent of oppression of function of marrow.

At in administration of drug in high doses (100–240 mg/sq.m) need of a dose decline depends on degree of a renal failure, on whether transplantation of haematopoietic stem cells, and from therapeutic need is carried out. As a rule, when performing high-dose therapy by Melphalanum without transplantation of haematopoietic stem cells at patients with a moderate renal failure (KK of 30-50 ml/min.) the dose is reduced by 50%. At a heavy renal failure high-dose therapy by Melphalanum without transplantation of haematopoietic stem cells is not recommended.

High-dose therapy by Melphalanum in combination with transplantation of haematopoietic stem cells was successfully performed even at the patients with an end-stage of a renal failure who are on a hemodialysis.

The data on pharmacokinetics existing now do not allow to recommend with confidence Melphalanum dose decline for intake at patients with renal failures, however at the beginning of therapy can be reasonable to reduce a dose before clarification of portability of drug.

At purpose of drug inside it is necessary to consider that as absorption of drug after intake varies, for the guaranteed achievement of therapeutic concentration careful increase in a dose to development of a miyelosupressiya can be required.

Rules of preparation of solution for injections

Solution prepares at the room temperature by mixing of the lyophilized powder with solvent which is applied to a bottle with Alkeran.

With the lyophilized Alkeran's powder it is necessary to add 10 ml of solvent to a bottle (in one step) and to stir up vigorously before full dissolution. The received solution contains 5 mg of anhydrous Melphalanum in 1 ml and has pH about 6.5.

The prepared Alkeran's solution for injections is insufficiently stable and has to be prepared just before use. Unused solution should be destroyed. The prepared Alkeran's solution cannot be stored in the refrigerator as it causes formation of a deposit.

Alkeran's solution for injections is entered only in/in except for cases when partial arterial perfusion is shown.

At in use it is recommended to enter Alkeran's solution slowly through the special closed access in infusional system against the background of bystry infusion of other solution. If introduction directly to quickly entered other solution is impossible, then Alkeran's solution can be dissolved in capacity for infusions.

Alkeran's solution is recommended to part only 0.9% with sodium chloride solution for injections and not to mix with the infusion solutions containing dextrose (glucose).

At further cultivation of solution of Alkeran for injections in infusion solution its stability decreases, and the speed of its degradation quickly increases at temperature increase of the environment. At the room temperature (about 25 °C) the general time from the moment of preparation of solution of Alkeran for injections before completion of its infusion should not exceed 1.5 h.

If in the prepared or weak solution of Alkeran opacification or crystallization appears, it should be destroyed.

It is necessary to be careful in order to avoid possible introduction of Alkeran not in a vein, and in surrounding fabrics. In case of the complicated access to peripheral veins the drug is administered in the central veins. High doses of Alkeran (with transplantation of haematopoietic stem cells or without it) are recommended to be entered into the central veins.

When using drug for partial arterial perfusions it is recommended to get acquainted with technique details in special literature.


Features of use:

Immunization by a live vaccine can sometimes cause development of an infection in the patient with the weakened immunity. For this reason use of live vaccines against the background of therapy by Melphalanum is not recommended.

At an ekstravazation Alkeran's solution for injections can cause local damage of the fabrics surrounding a vessel therefore it should not be entered directly into a peripheral vein. It is recommended to enter Alkeran's solution slowly against the background of bystry infusion through the special closed access in infusional system or into the central vein.

Considering high risk and need for a difficult maintenance therapy at treatment by drug, it is necessary to carry out to high-dose therapy by Alkeran only in the specialized centers having the corresponding conditions under observation of experienced specialists. At the patients receiving high-dose in/in therapy by Alkeran it is necessary to resolve an issue of preventive purpose of antibacterial drugs and if it is required, blood components. Before performing high-dose therapy by Melphalanum it is necessary to provide an adequate general condition of an organism and function of bodies.

Alkeran it is necessary to use with care at the patients who recently completed a course of radiation therapy or chemotherapy in connection with a possibility of strengthening of toxic influence on marrow.

At Alkeran's use it is necessary to implement recommendations about use of cytotoxic drugs.

Removal of Melphalanum at patients with a renal failure can decrease. Besides, at a renal failure there can be an oppression of a kostnogomozgovy hemopoiesis of uraemic genesis. In such cases the drug dose decline can be required, and patients have to be under careful observation of the doctor.

Aberation chromosomes were found in the patients receiving Alkeran.

Melphalanum, as well as other alkylating drugs, can cause development of a leukosis in the person. There are messages on an acute leukosis after long therapy by Melphalanum concerning an amyloidosis, a melanoma, a multiple myeloma, a macroglobulinemia, a cold agglyutininovy syndrome and cancer of an ovary. Comparative analysis of the patients with cancer of an ovary who were receiving and not receiving the alkylating drugs including Melphalanum, revealed reliable increase of incidence of an acute leukosis in the first group. Before Alkeran's appointment it is necessary to compare risk of development of a leukosis with potential therapeutic effect of drug.

Control of laboratory indicators

As Alkeran is myelosuppressive means, during therapy it is regularly very important to define number of uniform elements of blood, if necessary adjusting a dose or temporarily postponing administration of drug in order to avoid possible development of an excessive miyelosupressiya and risk of an irreversible aplasia of marrow. The quantity of blood cells can continue to decrease also after drug phase-out therefore at the first signs of too sharp decrease in number of leukocytes or thrombocytes treatment has to be temporarily stopped.

Rules of safe handling of drug

At the address with Melphalanum it is necessary to adhere to indications for the address with cytostatics according to local recommendations and/or regulations.

Alkeran's solution has to prepare under observation of the experienced druggist owning rules of safe handling of drug and familiar with its properties. Solution of Melphalanum has to prepare in aseptic conditions on the special equipment (in a laboratory case with a vertical extract), or if there is no that, in specially allocated isolated room in a drugstore or clinic. The personnel which prepare solutions or do injections have to put on special protective clothes: one-time gloves from surgical latex or polyvinylchloride of high quality (rubber do not approach), a surgical mask of the corresponding quality, goggles which should be washed carefully with water after use, a one-time apron.

During the work in aseptic conditions other clothes will be required.

When spraying or spilling solution the personnel dressed in the corresponding protective clothes have to wipe immediately a surface with wet one-time paper towels which at once are folded then in a container for dangerous wastes, and then destroy according to the established procedure. The surface on which drug got needs to be washed up a large amount of water.

At Melphalanum solution hit on skin it is necessary to wash out immediately and carefully it a large amount of cold water with soap; in such cases it is reasonable to see a doctor.

At contact with a mucous membrane of eyes immediately to wash out solution of chloride sodium for eyes and to see immediately a doctor. In the absence of solution of chloride sodium it is possible to use a large amount of water.

Rules of safe handling of Melphalanum tablets

At the address with dosage forms of Melphalanum it is necessary to observe the indications for the address with cytostatics which are available in local recommendations and/or the relevant regulations.

If the outside cover of a tablet is not damaged, then the address with tablets of Melphalanum is not accompanied by risk. Tablets of Melphalanum should not be broken.

Rules of destruction of drug

Alkeran's solution has to be destroyed according to the established requirements. In the absence of those it is subject to the same procedure of destruction, as well as other toxic chemicals, for example to high-temperature burning and deep burial.

Destruction of sharp objects (for example needles, syringes, infusional systems and ampoules) has to be carried out in rigid containers with a warning sign about danger. The personnel which are carrying out destruction have to be informed on respect for all precautions. Procedures of destruction have to conform to local normative requirements.

Tablets of Melphalanum destroy according to local normative requirements to destruction of tsitostatik.


Side effects:

Modern clinical data on the frequency of undesirable reactions when using this drug are absent. Frequency of undesirable reactions varies depending on the indication and the entered doses, and also from use of drug in a combination with other means.

For classification of frequency of undesirable reactions the following principles were used: very often - ≥0.1, it is frequent - ≥0.01, but <0.1, sometimes - ≥0.001, but <0.01, is rare - ≥0.0001, but <0.001, is very rare - <0.00001

From system of a hemopoiesis and lymphatic system: very often - oppression of a marrowy hemopoiesis with development of a leukopenia and thrombocytopenia; seldom – hemolitic anemia.

From immune system: seldom – allergic reactions (urticaria, hypostasis, skin rash, an itch and an acute anaphylaxis at the first and the subsequent introductions were noted infrequently, mainly at in/in therapy by Alkeran). There are messages on exceptional cases of a cardiac standstill at allergic reactions to Alkeran.

From respiratory system: seldom - intersticial pneumonia and pulmonary fibrosis (including with a lethal outcome).

From the alimentary system: very often - nausea, vomiting and diarrhea; when using the high-dose mode – stomatitis; seldom - damages of a liver, beginning from change of activity of functional hepatic trials to clinically manifest hepatitis and jaundice, a veno-occlusal disease after high-dose therapy, stomatitis at use of standard doses. At parenteral administration: diarrhea, nausea, vomiting are dozolimitiruyushchy factors of toxicity at the patients receiving in/in high-dose therapy by Alkeran together with transplantation of haematopoietic stem cells. The previous therapy by cyclophosphamide, apparently, reduces expressiveness of the symptoms from a GIT caused by a high dose of Alkeran. At intake: according to the available data, to 30% of the patients receiving Melphalanum inside in standard doses note side effects from the alimentary system, such as nausea and vomiting.

Dermatological reactions: very often – an alopecia when performing high-dose therapy, it is frequent – an alopecia at purpose of standard doses; seldom - makulo-papular rash and a skin itch.

From an urinary system: often - tranzitorny reliable increase in level of urea in blood at patients with a multiple myeloma with a renal failure.

Others: at parenteral administration it is very frequent – subjective tranzitorny feeling of heat and/or a pricking.


Interaction with other medicines:

In/in introduction of Melphalanum in high doses along with Acidum nalidixicum led at children to a lethal outcome owing to development of a hemorrhagic coloenteritis.

At patients to whom before transplantation of haematopoietic stem cells in/in entered Melphalanum in high doses and in the subsequent appointed cyclosporine for prevention of reaction "a transplant against the owner", cases of a renal failure are described.

Pharmaceutical incompatibility

Solution of drug is incompatible with the infusion solutions containing dextrose (glucose). It is recommended to be entered only in solution of sodium chloride of 0.9% for in/in infusions.


Contraindications:

— hypersensitivity to Melphalanum.

Use of drug ALKERAN at pregnancy and feeding by a breast


It is necessary to avoid use of Melphalanum at pregnancy, especially in the I trimester. In each individual case the potential risk for a fruit has to correspond to the expected advantage for mother.

The women receiving Alkeran have to stop breastfeeding.

If any of partners Alkeran receives, it is necessary to use reliable methods of contraception.

Teratogenic potential of Alkeran was not studied. Taking into account its mutagen properties and structural similarity to the known teratogenic connections, it is not excluded that Alkeran can cause inborn malformations in the children who were born at the patients receiving this drug.

At considerable number of the women who did not reach a menopause, Alkeran suppresses function of ovaries that causes an amenorrhea. Some data indicate a possibility of adverse influence of Alkeran on a spermatogenesis, therefore, at its use development of passing or resistant sterility in men is not excluded.

Use at renal failures
At a renal failure the clearance of Melphalanum can decrease though strongly varies. At in administration of drug in standard doses (8–40 mg/sq.m) patients with a moderate or heavy renal failure are recommended to reduce an initial dose by 50%, and further to select a dose depending on extent of oppression of function of marrow.

At in administration of drug in high doses (100–240 mg/sq.m) need of a dose decline depends on degree of a renal failure, on whether transplantation of haematopoietic stem cells, and from therapeutic need is carried out. As a rule, when performing high-dose therapy by Melphalanum without transplantation of haematopoietic stem cells at patients with a moderate renal failure (KK of 30-50 ml/min.) the dose is reduced by 50%. At a heavy renal failure high-dose therapy by Melphalanum without transplantation of haematopoietic stem cells is not recommended.


Overdose:

Symptoms: the first manifestations of acute overdose of Alkeran at in introduction are nausea and vomiting, damage of a mucous membrane of a GIT with diarrhea, sometimes hemorrhagic can develop. At intake the most probable first symptoms of acute overdose are side reactions from a GIT, including nausea, vomiting and diarrhea. The main toxic action of Melphalanum (both at intake, and at parenteral administration) consists in suppression of a marrowy hemopoiesis with development of a leukopenia, thrombocytopenia and anemia.

Treatment: if necessary it is necessary to hold the general events of the supporting character, together with hemotransfusions and a platelet concentrate, and also to resolve an issue of hospitalization of patients for performing anti-infectious therapy and purpose of stimulators of a hemogenesis. The specific antidote does not exist. It is necessary to control carefully indicators of peripheral blood within not less than four weeks after overdose, signs of their normalization will not appear yet.


Storage conditions:

Packaging with drug in shape for parenteral administration should be stored in protected from light and the place, unavailable to children, at a temperature not above 30 °C. A period of validity of the lyophilized powder for solution preparation - 3 years.

Drug in the form of tablets should be stored in the place, unavailable to children, at a temperature from 2 to 8 °C. A period of validity of tablets – 2 years.

Drug should not be used after the termination of the period of validity specified on packaging.


Issue conditions:

According to the recipe


Packaging:

• tablets, film cover, 2 mg: 25 - П N015839/01, 21.07.08. Validity period рег. уд. it is not limited. VED. DLO.

• lyophilisate for пригот. solution for intravascular introduction of 50 mg: фл. 1 in set. with solvent - P N014836/01, 13.08.07. Validity period рег. уд. it is not limited. VED. DLO.



Similar drugs

Препарат Мелфалан. Glaxo Operetaions UK Limited (Глаксо Оперейшнс ЮК Лимитед) Великобритания

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The alkylating means.





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