Cyclophosphan (powder for solution for injections preparation 0,2 g)
Cyсlophosphanum 0,2 pro injectionibus
International nonproprietary name
Cyclophosphamide.
Pharmacotherapeutic group
Cytostatic (antitumor) drug.
Pharmacological action
Pharmacodynamics
The preparation is referred to a group of alkylating substances that are derivatives of bis-(b-chloroethane)-amine. Cyclophosphan possesses selective antitumor activity. Cytostatic action of the preparation is realized directly in tumor cells. At penetration into tumor cells Cyclophosphan quickly breaks down under an action of phosphatases (phosphoamidases) containing in them in abundance with formation of the active component possessing alkylating action.
Cyclophosphan has also immunodepressive effect. Similarly to other cytostatic agents the preparation suppresses proliferation of lymphocytic clones participating in the immune answer. At that, Cyclophosphan acts mainly on B-lymphocytes.
Pharmakokinetics
Cyclophosphan passes through cell membrane by passive diffusion. In patients with malignant neoplasms after intravenous introduction in a dose of 0,006-0,008 g/kg the preparation quickly penetrates into tissues and fluids of an organism. The period of half-elimination from plasma is 6,5 h. Cyclophosphan is non-uniformly distributed in an organism: it accumulates mainly in spleen, lungs, marrow, liver and kidneys.
In patients with malignant neoplasms without functional liver and kidneys failure approximately 88 % of the preparation is exposed to metabolism with formation of alkylated derivatives. In liver at presence of triphosporpyridindinucleotide and molecular oxygen Cyclophosphan changes in 4-oxycyclophosphamide, and di-(2- chloroethane)-amide and acrolein are formed from itstautomeric form. Alongside with that there is an oxidation of 4-oxycyclophosphamide in less toxic 4-oxycyclophosphaneand carboxyphosphamide.
Cyclophosphan and its metabolites are eliminated with urine, thus, approximately 20 % of introduced preparation are eliminated in non-changed form, the rest - in a form of alkyl derivatives. 2/3 of introduced preparation are eliminated during the first 8 h. After single intravenous introduction the active metabolites can be determined during 26-30 h.
The preparation concentration toxic for baby marrow can be accumulated in milk of nursing mothers.
Indications
Preparation is administrated at small cell lung cancer, cancer of ovaries, cancer of mammary gland, reticulosarcoma, lymphosarcoma, chronic lymphoid leukosis, acute lymphoblastic leukosis, multiple myeloma, Wilms' tumor, bone reticulosarcoma, Ewing's tumor, angiosarcoma.
Dosage and method of administration
Preparation is introduced intravenously, intramusculary, and also into cavities.
The solutions for injections are prepared directly before use using sterile water for injections.
Regimen of dosage is individual.
Various schemes of treatment can be applied:1) per 200 mg (3 mg/kg) daily or per 400 mg (6 mg/kg) every other day (intravenously or intramusculary); 2) per 1 g(15 mg/kg) 1 time in 5 days intravenously; 3) per 2-3 g(30-45 mg/kg) 1 time in 2-3 weeks intravenously. The course dose at all regimens of treatment is 6-14 g. Other schemes of treatment can also be used.
At liquid accumulation as a result of cancer process in abdominal and pleural cavities in addition to intravenous injections 0,4-1,0 gCyclophosphan (at each puncture) can be introduced into cavities. At that quantity of the preparation introduced intravenously, should be accordingly reduced.
After the termination of the basic course of treatment by Cyclophosphan maintenance therapy can be applied: per 0,1-0,2 gof the preparation 2 times a week intravenously or intramusculary.
As an immunodepressive agent Cyclophosphan is used apply usually at the rate of 1,0-1,5 mg/kg (50-100 mg day), at good tolerance - up to 3-4 mg/kg.
The use of Cyclophosphan can cause suppression of leukopoiesis. It is impossible to begin treatment by the preparation at leucocytes’ number of less than3,5×109/Land thrombocytes’ number less than120×109/L. During treatment it is necessary to carry out blood test not less often than 2 times a week. At decrease of leucocytes number up to2,5×109/Land thrombocytes up to100×109/L the treatment by Cyclophosphanum should be withdrawn.
At sharply expressed leukopenia the transfusion of blood or leukocyte and thrombocyte mass, administration of vitamins and hemopoiesis stimulators should be carried out. The transfusion of stimulating blood amounts (100-125 ml once a week) is recommended during all course of treatment.
Side effects
Nausea and vomiting are often at application of the preparation (especially at overdosage). For these phenomena decrease the use of antiemetic agenst, and also introduction of pyridoxine (intramusculary per 0,05 g) is recommended. Often (up to 90 % of cases) in 18-20 days after the beginning of Cyclophosphan use the partial or full alopecia is observed; hair begins to grow after the termination of the preparation introduction. Sometimes there is giddiness, impairment of vision, dysuric phenomena, hematuria. The dysuric phenomena usually pass in 4-5 days. The patients often complain of ostealgia continuing to 2-3 weeks.
At intrapleural introduction of the preparation for 2-3 days the body temperature can raise, cough and pains in a thorax can appear.
Contraindications
The expressed cachexia, anemia, leukopenia, thrombocytopenia, serious diseases of heart, liver, kidneys, terminal of disease.
Safety measures
At occurrence of following signs: chill, fever, cough or hoarseness, pain in a bottom part of back or in a side, the painful or complicated urination, bleedings or hemorrhages, black stool, blood in urine or feces, it is necessary to immediately consult with the doctor.
Interactions with other medicinal preparations
The preparation increases cardiotoxicity of adriamycin. At preliminary reception of Allopyrinol the time of Cyclophosphan half-elimination from plasma is decreased, and the amount of alkyl metabolites is increased. Allopyrinol strengthens myelodepression, caused by Cyclophosphan.
Therapeutic effect of Cyclophosphan is increased by barbiturates, tricyclic antidepressants, Theophyllin, Chingamin, thyroid hormones; is reduced (including toxic effect) by glucocorticoids and Chloramfenicol.
The form of release
Powder per 0,2 gfor injections in vials.
Solution of 0,25 % Zinc sulfate and 2 % Boric acid (eye drops)
Solutio Zinci sulfatis 0,25 % et Aсidi borici 2 % (guttae ophthalmicae)
International nonproprietary name
Zinc sulfate. Boric acid.
Zinci sulfas. Aсidum boricum.
Pharmacotherapeutic group
Agents for of eyes diseases treatment. Antimicrobial preparations.
Composition
1 ml of sterile solution (eye drops) contains 2,5 mg of zinc sulfate, 20 mg of boric acid.
Pharmacological action
Pharmacodynamics
The preparation has astringent, drying, antiseptic effect.
Drying and astringent action develops depending on depth of albuminate penetration which are formed as a result of coagulation of proteins by zinc ions.
Antimicrobial activity is a consequence of microorganisms’ proteins coagulation.
Pharmakokinetics
Boric acid is adsorbed through the damaged skin, mucosa, passes into many organs and tissues and can collect in them. It is slowly extracted, and can cumulate. It is eliminated with urine.
Zinc sulfate at use in a form of eye drops is absorbed in microquantities.
Indications
Treatment of blepharites, conjunctivitises, prophylaxis of bacteria infection at foreign body penetration in conjunctival cavity.
Dosage and method of administration
Instill in conjunctival bag per 1-2 drops 2-4 times a day.
Special indications
It is necessary to avoid penetration of the preparation on mucosa (probably intensifying of an absorption of active components and displays of their toxic and irritating action).
Side effects
The irritation and pain in eyes are possible. If these phenomena last more than 3 days, it is necessary to consult with a doctor.
Contraindications
Hypersensitivity to the preparation components. The preparation should not be used at pregnancy, breast feeding and in children.
Interactions with other medicinal preparations
Zinc salts reduce effect of Penicillamine, form chelates with Tetracycline.
Overdosage
Signs of a chronic intoxication are possible at long use in doses substantially exceeding therapeutic doses. Nausea, fever, local edema of tissues can be observed, kidneys function failure, electrolytesdisbalance in plasma are possible.
In this case the use of the preparation should be withdrawn.
The form of release
Sterile 0,25 % zinc sulfate and 2 % boric acid solution (eye drops) in 1 ml tube-droppers.
