Vinblastine

General characteristics. Structure:

Composition of lyophilisate
Active ingredient: vinblastine sulfate of 5 mg
Excipients: no
Composition of solvent: sodium chloride, water for injections.

Pharmacological properties:

Pharmacodynamics. Vinblastine is the alkaloid emitted from a plant of the sort Vinca (periwinkle). Vinblastine blocks mitotic division of cells in metaphase of a cellular cycle. Has effect, contacting microtubules by means of braking of formation of mitotic spindles. In tumor cells synthesis of DNA and RNA by means of braking of a DNA-dependent RNA polymerase selectively oppresses.

Pharmacokinetics. After intravenous administration it is quickly distributed in fabrics. Does not get through a blood-brain barrier. Communication with proteins – 80%. It is metabolized in a liver. Respectively 3,7 minutes, 1,6 hours and 24,8 hours are brought out of an organism in three phases with elimination half-lives duration (average values), it is preferential with bile. A small amount of vinblastine in not changed look and in the form of metabolites is defined in urine.

Indications to use:

– Hodzhkin's disease
– Nekhodzhkinsky lymphoma
– Chronic lymphoid leukosis
– Germinogenny tumors of a small egg and ovaries
– Bladder cancer
– Kaposha's sarcoma
– Disease to Letterera-Siwa (histiocytosis of X)
– Fungoid mycosis (generalized stages).

Route of administration and doses:

Only for intravenous administration (it is necessary to avoid an ekstravazation).
It is forbidden to enter intratekalno!
The dose is selected taking into account specific features of the patient and the applied scheme of chemotherapy, being guided by data of special literature.
The usual dose makes:
– for adults: 5,5-7,4 mg/sq.m of a body surface
– for children: from 3,75 to 5 mg/sq.m of a body surface
The drug is administered once a week or 1 time in 2 weeks.
Also the modes of gradual increase in weekly doses can be used:
– for adults: the 1st dose – 3,7 mg/sq.m, each subsequent weekly dose, at quantity of leukocytes not less 4000/mkl blood, increases by 1,8-1,9 mg/sq.m of a body surface before achievement of the maximum single dose of 18,5 mg/sq.m
– for children: weekly increase in doses on 1,25 mg/sq.m is carried out by the same principle, as at adults, since an initial dose of 2,5 mg/m of a body surface and to the maximum dose of 12,5 mg/sq.m.

Doses raise until the quantity of leukocytes does not decrease to 3000/mkl, or the tumor size will not decrease, or the maximum single dose then pass to maintenance doses which there is less final value of the last dose for adults on 1,8-1,9 mg/sq.m and for children on 1,25 mg/sq.m of a body surface which are entered 1 time in 7-14 days will not be reached.

At bilirubin level in blood serum it is higher than 3 mg / 100 of ml (50 µmol/l) the dose decline for 50% is recommended.
Apply freshly cooked solution for what bottle contents with the lyophilized powder are dissolved in the enclosed solvent. Just before introduction drug if necessary can be divorced with 0,9% chloride sodium solution (other solutions are not recommended to be applied) to concentration of 1 mg / 1 in ml.

Features of use:

Treatment by Vinblastine can be carried out only under control of the doctor having experience of use of antineoplastic chemotherapy
Before to begin an injection, it is necessary to be convinced that the needle is in a vein. At an ekstravazation of vinblastine it is necessary to stop administration of drug at once; the remained solution with drug needs to be entered into other vein. It is recommended to enter hyaluronidase into the struck area.
During treatment regular control of number of leukocytes, thrombocytes and level of hemoglobin is necessary.
At decrease in number of leukocytes to 3000/mkl, treatment should be stopped.
In the course of treatment control of activity of liver enzymes and content of bilirubin in blood serum is also necessary.
At emergence of symptoms of neurointoxication treatment by Vinblastine should be stopped.
In order to avoid an acute urate nephropathy it is regularly necessary to control the level of uric acid in blood serum and to provide sufficient consumption by the patient of liquid. If necessary it is recommended to appoint Allopyrinolum.
Women of childbearing age during treatment by vinblastine need to apply non-hormonal reliable methods of contraception.
Performing vaccination is forbidden by a live virus vaccine of the patients who are on treatment by vinblastine.
At accidental hit of vinblastine in their eyes it is necessary to wash out immediately carefully water for prevention of strong irritation or a possible keratohelcosis.
Some side effects of drug (neurotoxicity) can negatively influence ability of driving and performance of potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions. In this regard at control of vehicles and mechanisms it is necessary to be careful.

Side effects:

From system of a hemopoiesis: most often a leukopenia, a granulocytopenia (the lowest level is noted in 5-10 days after the last introduction, the complete recovery usually occurs during the next 7-14 days); more rare thrombocytopenia, anemia.
From system of digestion: stomatitis, pharyngitis, a loss of appetite, nausea, vomiting, a lock, diarrhea, an abdominal cavity pain, paralytic impassability of intestines, a hemorrhagic coloenteritis, bleedings from earlier diagnosed digestive tract ulcers.
From a nervous system: paresthesias, decrease or loss of deep tendon jerks, peripheral neuritis, a depression, a headache, spasms, dizziness, a diplopia, weakness, pain in jaws, neuritis of the VIII pair of cherepnomozgovy nerves (partial or full deafness, dizziness, a nystagmus).
From cardiovascular system: increase in arterial pressure; myocardium ischemia, including stenocardia or a myocardial infarction (usually at simultaneous use with Bleomycinum and Cisplatinum); a mikroangiopatiya (Reynaud's syndrome at simultaneous use of Bleomycinum);
From respiratory system: a bronchospasm (usually, at simultaneous use with mitomitsiny) with acute respiratory insufficiency, cyanosis, an asthma and it is frequent with formation of pulmonary infiltrates and a pneumonitis.
From skin and skin appendages: alopecia, small tortoiseshell.
Local reactions: pain or reddening in the place of an injection, phlebitis; at hit of drug under skin – an inflammation of a hypodermic fatty tissue, and, perhaps a necrosis.
Others: hyperuricemia, urate nephropathy; weakness, increased fatigue, a mialgiya, an ossalgiya, pain in the field of tumoral nodes; azoospermism and amenorrhea (sometimes irreversible). At purpose of doses above recommended the syndrome of inadequate secretion of antidiuretic hormone is noted.

Interaction with other medicines:

Simultaneous use of neurotoxic drugs (isoniazid, L-asparaginase) is forbidden.
It is necessary to be careful at simultaneous use of ototoksichny drugs.
At simultaneous use with mitomitsiny it is necessary to be careful because of possible development of an acute bronchospasm.
At a concomitant use with vinblastine plasma concentration of Phenytoinum decreases that can lead to decrease in its anticonvulsant activity.
At simultaneous use with Bleomycinum development of a syndrome of Reynaud is possible. At use of vinblastine in a combination with Bleomycinum and Cisplatinum cases of a myocardial infarction, disturbance of cerebral circulation At use in a combination with the drugs containing platinum are noted the risk of defeat of the VIII couple of ChMN increases.

Antigouty medicines (Allopyrinolum, colchicine, пробеницид, сулфинпиразон) can cause increase in level of uric acid in blood; correction of their doses for the purpose of prevention of development of a hyperuricemia can be required; to prevention and treatment of the hyperuricemia caused by vinblastine it is more preferable to apply Allopyrinolum in order to avoid development of an acute urate nephropathy as a result of use of uricosuric antigouty drugs.
Thrombocytopenic and leykopenichesky effects of vinblastine strengthen drugs which, in turn, too capable to have similar effect if their use is carried out along with vinblastine or precedes it; correction of a dose of vinblastine taking into account a blood picture can be required. The interval between the treatment termination by vinblastine and vaccination by an attenuirovanny or live virus vaccine depends on type and degree of medicinal immunosuppression, a basic disease and other factors and 3-12 months last.

Contraindications:

- hypersensitivity to vinkaalkaloida or to any other component of drug,
- the expressed oppression of function of marrow,
- bacterial and viral infections,
- pregnancy and period of a lactation.

With care: recently carried out or at the same time carried out myelosuppressive chemotherapy or radiotheraphy, a leukopenia, thrombocytopenia, abnormal liver functions, a hyperuricemia, advanced age.

Overdose:

Symptoms: development of side effects in more expressed form.
Treatment: there is no antidote, carrying out a symptomatic and maintenance therapy. The following events are recommended: at development of a syndrome of inadequate secretion of antidiuretic hormone – restriction of consumption of liquid and purpose of diuretics; purpose of anticonvulsants; control of function of cardiovascular system; careful control of a picture of blood, if necessary – hemotransfusion; use of enemas and laxative drugs (prevention of impassability of intestines).
The hemodialysis is inefficient at Vinblastine overdose.

Storage conditions:

At a temperature of 2-8 °C, in the place protected from light. To store in the place, unavailable to children!

Period of validity
For lyophilisate: 2 years.
For solvent: 5 years
On a cardboard pack the lyophilisate period of validity is specified.
Not to use drug expired. 

Issue conditions:

According to the recipe

Packaging:

The lyophilisate for preparation of solution for intravenous administration containing 5 mg of vinblastine of sulfate in bottles of brown glass on 5 mg with the enclosed solvent (0,9% chloride sodium solution) in ampoules of colourless glass on 5 ml. On 1 bottle and 1 ampoule in the plastic pallet. 10 plastic pallets in a cardboard pack with the application instruction.