Alkeran

Alkeran – antineoplastic drug.

Form of release and structure

• Tablets, film coated: almost white or white color, round, biconvex, on one party the text "GX EH3", is applied on another – "And"; a kernel of a tablet of almost white or white color (on 25 pieces in glass bottles of dark color, in a cardboard pack 1 bottle);
• The lyophilized powder for preparation of solution for injections: white or almost white weight without visible particles at dissolution; solvent – transparent colourless liquid with an alcohol smell (on 50 mg in glass bottles, in a cardboard pack 1 bottle complete with 1 bottle of solvent (10 ml) in a plastic case).

Contains in 1 tablet of Alkeran:

• Active ingredient: Melphalanum – 2 mg;
• Auxiliary components: silicon dioxide colloid, magnesium stearate, кросповидон, cellulose microcrystallic;
• Cover: Опадрай white YS-1-18097-A (titanium dioxide, gipromelloz, macrogoal).

With the lyophilized powder for preparation of solution for injections contains in 1 bottle:

• Active ingredient: Melphalanum (in the form of a hydrochloride) – 50 mg;
• Auxiliary components: Acidum hydrochloricum, K12 povidone.

Composition of solvent: ethanol, propylene glycol, sodium citrate, water for injections.

Indications to use

Tablets, film coated

• Multiple myeloma;
• Widespread adenocarcinoma of an ovary;
• Carcinoma of a mammary gland;
• Osler's disease.

The lyophilized powder for preparation of solution for injections

• Widespread cancer of an ovary;
• Multiple myeloma;
• The localized sarcoma of soft tissues of extremities;
• The localized melanoma of extremities;
• Widespread neuroblastoma at children.

Contraindications

• Breastfeeding period;
• Individual intolerance of Melphalanum.

During pregnancy, especially the I trimester, Alkeran's use should be avoided, except cases, life-threatening swear.

Route of administration and dosage

Alkeran's appointment has to be made by the oncologist with experience of treatment by cytotoxic drugs of malignant new growths.

Tablets, film coated
Pill is taken inside, swallowing entirely.

The dose and the period of treatment are appointed by the doctor on the basis of clinical indications.

As absorption of Melphalanum can change, for ensuring therapeutic concentration of drug the dose can be raised to emergence of signs of a miyelosupressiya gradually.

The recommended dosing:

• Multiple myeloma: the daily dose is appointed from calculation for 0,15 mg to 1 kg of weight of the patient, it should be divided into several receptions in day, a course – 4 days. The course of treatment is repeated with an interval of 6 weeks;
• Adenocarcinoma of ovaries: on 0,2 mg on 1 kg a day, duration of one course – 5 days, treatment alternate to a break in 4-8 weeks or proceeding from clinical indications of recovery of function of marrow;
• Carcinoma of a mammary gland: on 0,15 mg on 1 kg of weight or on 6 mg on 1 ^sq.m of a body surface of the patient a day, duration of one course – 5 days, courses repeat every 6 weeks. In need of decrease in toxic action by a marrowy hemopoiesis the dose is reduced;
• Osler's disease: remission induction – on 6-10 mg a day within 5-7 days, then the dose is reduced to 2-4 mg a day. The dosing mode for a maintenance therapy – on 2-6 mg once a week.

The lyophilized powder for preparation of solution for injections
Ready solution from the lyophilized powder is applied for intravenous (in/in) and, in exceptional cases, intra arterial (in / and) by introductions (by means of partial arterial perfusion).

Because of limited stability solution prepare before direct introduction at the room temperature by single-step addition in a bottle with the lyophilized powder 10 ml of solvent and vigorous stirring before full dissolution. The maintenance of anhydrous Melphalanum in 1 ml of the received solution makes 5 mg with level рН about 6,5.

For additional cultivation of solution it is recommended to use only 0,9% chloride sodium solution for injections. With the solutions containing a dextrose, Alkeran it is impossible to mix!

Stability of solution decreases: at a temperature above 25 °C; the subsequent cultivation in infusion solution; a pro-procession more than 1,5 hours from the moment of preparation of solution before completion of its introduction. In case of opacification or crystallization of solution – it should be destroyed.

Introduction can be made in peripheral and central veins, for high doses of drug it is recommended to use the central veins, the ekstravazation cannot allow.

It is required to enter into solution slowly against the background of bystry drop administration of other solution.

Use of solution of Alkeran is shown in the form of monotherapy and in a combination with other cytotoxic means, Prednisolonum in certain cases is in addition appointed.

The recommended dosing:

• Multiple myeloma: in a combination with cytostatics – on 8-30 mg on 1 ^sq.m of a body surface of the patient at an interval of 2-6 weeks; monotherapy – on 16 mg on 1 ^sq.m (0,4 mg on 1 kg of weight) 1 time in 4 weeks. Repeated introduction is shown only at recovery of indicators of peripheral blood for this period. High-dose therapy – once in a dose of 100-200 mg on 1 ^sq.m (2,5-5,0 mg on 1 kg). After introduction of the doses exceeding 140 mg on 1 ^sq.m sick change of autologous marrow is required. At a renal failure the dose is lowered by 50%;
• Adenocarcinoma of ovaries: monotherapy – 1 mg on 1 kg of weight (about 40 mg on 1 ^sq.m) 1 time in 4 weeks; in a combination with cytostatics – on 0,3-0,4 mg on 1 kg (12-16 mg on 1 ^sq.m) 1 time in 4-6 weeks;
• The progressing neuroblastoma at children: at monotherapy, a combination to cytostatics and/or radiation therapy (under protection of autologous marrow) – on 100-240 mg into 1 ^sq.m once or having divided it into 3 procedures of introduction within 3 days in a row.

At sarcoma of soft tissues and a malignant melanoma it is shown in / and Alkeran's introduction using hyper thermal partial perfusion.

It is possible to apply high doses of drug at patients of advanced age only at normal functioning of internals and a satisfactory general condition of the patient.

At the moderated and expressed renal failure the initial dose should be lowered by 50%, to select doses for repeated introduction taking into account extent of oppression of function of marrow. At therapy using high doses of drug need of dose adjustment depends on extent of functional disturbance of kidneys, the medical purpose and on whether infusion of autologous stem cells of marrow is carried out. Usually, at the clearance of creatinine (CC) of 30-50 ml/min. the dose is lowered by 50%, treatment is accompanied with introduction of enough liquid and carrying out an artificial diuresis. At KK high doses of Alkeran it is not recommended to appoint less than 30 ml/min.

Side effects

• System of a hemopoiesis and lymphatic system: very often – oppression of a marrowy hemopoiesis, thrombocytopenia, a leukopenia; seldom – hemolitic anemia;
• Immune system: seldom – allergic reactions (skin rash, an itch, a small tortoiseshell, hypostasis, an acute anaphylaxis, is more often at parenteral therapy), a cardiac standstill;
• Respiratory system: seldom – pulmonary fibrosis, intersticial pneumonia (up to a lethal outcome);
• Alimentary system: very often – nausea, vomiting, diarrhea; against the background of high-dose therapy – stomatitis; seldom – damages of a liver, increase in activity of functional hepatic trials, hepatitis, jaundice, against the background of standard doses – stomatitis, a veno-occlusal disease (after high-dose therapy);
• Dermatological reactions: very often – an alopecia against the background of high-dose therapy, it is frequent – an alopecia at standard doses; seldom – a skin itch, makulopapulezny rash;
• Urinary system: often – increase in level of urea in blood (at a renal failure at patients with a multiple myeloma);
• Other reactions: very often – feeling of a pricking and/or heat at parenteral administration.

Special instructions

Immunization by a live vaccine against the background of use of Melphalanum is not recommended as there is a risk of development of an infection in patients with the weakened immunity.

Alkeran's solution should be entered slowly into the central vein or through the special closed access in infusional system against the background of bystry infusion. Ekstravazation can cause local damage of fabrics and surrounding vessels therefore direct introduction to a peripheral vein is not desirable.

Carry out to introduction of high-dose therapy only in the specialized centers, under observation of experienced specialists, on condition of the general satisfactory condition of the patient and adequate function of his bodies. The difficult supporting and preventive treatment including antibacterial drugs and, if necessary, blood components is shown to patients.

Because of risk of strengthening of toxic impact on marrow, it is required to be careful at Alkeran's use for the patients who recently completed a course beam or chemotherapy.

As Melphalanum can cause development of a leukosis, at its appointment it is necessary to compare the expected effect of use of drug with risk of development of a leukosis.

The myelosuppressive effect of drug demands to accompany treatment with regular control of laboratory indicators of number of uniform elements of blood. On the basis of these data during therapy regular correction or transfer of introduction of the next dose of drug is made to reduce probability of an irreversible aplasia of marrow and development of an excessive miyelosupressiya.

The first signs of sharp decrease in number of thrombocytes or leukocytes are the basis for the temporary termination of treatment as process of decrease in quantity of blood cells can continue also after drug withdrawal.

During use of drug in the form of solution or tablets by one of partners, it is necessary to use reliable methods of contraception.

Alkeran's use demands observance of the rules provided for safe handling of cytostatics. Preparation of solution has to take place under observation of the experienced specialist, in the isolated room, in a special laboratory case with a vertical extract, in aseptic conditions. For holding a procedure the medical staff has to be dressed in sterile clothes and is equipped with a one-time apron, gloves (from qualitative polyvinylchloride or surgical latex, but not rubber), the surgical mask and goggles which are carefully washed up by water after each use.

At accidental spraying solution is immediately collected by wet paper towels which then send for utilization in a container for dangerous wastes. The surface is carefully washed out water.

If solution gets on skin, it needs to be washed away carefully cold water with soap and to see a doctor.

In case of hit of solution on a mucous membrane of eyes, they should be washed out solution of chloride sodium for eyes or a large amount of water at once and to see immediately a doctor.

Use of tablets demands from sick observance of rules according to the address with cytostatics. Danger is constituted by a tablet with the broken outside cover, tablets of Melphalanum is strictly forbidden to break.

The medical staff has to observe requirements for destruction of solution, tablets, ampoules and procedural tools (syringes, needles, infusional systems).

Medicinal interaction

Contraindicated simultaneous in/in introduction at children of high doses of Melphalanum with Acidum nalidixicum as it causes development of a hemorrhagic coloenteritis with a lethal outcome.

Purpose of cyclosporine after transplantation of haematopoietic stem cells and in/in introductions Melphalanum in high doses causes a renal failure.

Terms and storage conditions

To store in the place protected from light, at a temperature: tablets – 2-8 °C, the lyophilized powder – to 30 °C. To protect from children.

Period of validity: tablets – 2 years; the lyophilized powder – 3 years.