Before intravenous administration, the contents of the vial are diluted with 0.9% sodium chloride solution or 5% dextrose solution in a volume 10 times the volume of the vial to a final concentration of at least 0.5 mg / ml. To do this, the required amount of busulfan is taken with a syringe with a needle and a filter with a pore size of 5 microns (supplied with the drug), after which the needle is changed and the contents of the syringe are introduced into the container with a pre-prepared solution of 0.9% sodium chloride or 5% dextrose solution. In all cases, you should enter busulfan in the solvent, and not vice versa. The resulting solution is mixed by inverting.
It is not recommended fast infusions of busulfan. Use infusion pumps. Before and after each infusion, the catheter should be rinsed with 5 ml of 0.9% sodium chloride or 5% dextrose solution.
Patients with hyperuricemia and / or hyperuricosuria need correction of these conditions before treatment with busulfan.
With the possible development of delayed myelotoxicity, it is recommended to stop busulfan treatment or reduce its dose at the first sign of a sudden decrease in the number of leukocytes (in particular, granulocytes) in order to prevent irreversible myelosuppression.
Some patients may be more susceptible to busulfan and demonstrate rapid myelosuppression. Frequent and careful monitoring of peripheral blood parameters is necessary. Reducing the number of leukocytes has an exponential character and the construction of a semilogarithmic dependence of the weekly decrease in the number of leukocytes allows one to predict the time of reaching their number to 15 × 109/ l and cancellation of the drug.
Cytological studies of the lungs, bladder, breast, cervix, lymph nodes, pancreas and thyroid gland, adrenal glands,bone marrow - the dysplasia of cells, induced by busulfan, can be expressed and make it difficult to interpret cytological preparations.
Busulfan causes myelosuppression, which increases the incidence of microbial infections, slows the healing of wounds and increases bleeding gums. It is necessary, if possible, to complete all dental work before chemotherapy begins and to resume them only after the resolution of myelosuppression.
Dimethylacetamide (a solvent included in the formulation of busulfan) can cause an increase in the activity of transaminases and the appearance of neurologic symptoms.
The diluted busulfan solution is stable for less than 8 hours at room temperature (25 ° C) and less than 12 hours - when stored in a refrigerator. It is necessary to complete the infusion by this time.
The tablet form of the preparation is stored in a tightly-closed container at a temperature below 40 ° C (preferably 15-25 ° C) unless otherwise directed by the manufacturer.
The solution for intravenous administration is stored at a temperature of 2-8 ° C.
The application is possible only under the supervision of a physician with experience in chemotherapy.
Before and during the treatment (at short intervals) it is necessary to determine the level of hemoglobin or hematocrit, the number of leukocytes (total, differential), platelets, activity of alanine aminotransferase, alkaline phosphatase, bilirubin level, uric acid concentration, constant monitoring of kidney and lung function.
If the following symptoms occur: chills, fever, cough or hoarseness, pain in the lower back or in the side, painful or difficult urination, bleeding or hemorrhage, black stools, blood in the urine or feces, consult a doctor immediately.
Leukopenia develops from 10-15 days after the start of therapy (before a short-term increase in the number of leukocytes is observed), the lowest level is observed on the 11th-30th day of treatment (it may decrease within 1 month after drug discontinuation), the level of leukocytes is restored during the next 12- 20 weeks (with severe myelodepression, treatment should be discontinued until symptoms of hematotoxicity are eliminated). With mielodepression (pancytopenia) after busulfan withdrawal, the restoration of the number of uniform elements to the normal level occurs within 1 month - 2 years.
In case of nausea and vomiting, busulfan should be continued, at the first signs of interstitial pneumosclerosis, treatment should be discontinued. Bronchopulmonary dysplasia with the development of pneumosclerosis, accompanied by a decrease in the vital function of the lungs and elasticity of the lung tissue, can develop in 8 months - 10 years (on average 4 years) after the start of treatment, within 6 months after diagnosis is possible fatal outcome.
When thrombocytopenia occurs, extreme caution is recommended when performing invasive procedures, regular examination of the sites of intravenous injections, skin and mucous membranes (to detect signs of bleeding), limiting the frequency of venous punctures and refusing intramuscular injections, monitoring blood in urine, vomit, feces. Such patients need to shave with care, do a manicure, brush their teeth, use dental floss and toothpicks, and perform dental procedures; should prevent constipation, avoid falls and other injuries, as well as taking alcohol and acetylsalicylic acid, increasing the risk of gastrointestinal bleeding.
In order to prevent nephropathy due to increased uric acid formation (occurs most often in the initial stage of treatment), it is necessary to consume enough fluids, increase diuresis, prescribe allopurinol (in some cases), and use drugs that cause alkalinization of urine.
In patients with increased seizure activity, treatment should be performed under the cover of anticonvulsants (preferably benzodiazepines, since enzyme inducers, for example phenytoin, can increase the clearance of busulfan and reduce its effectiveness).
If the reception was missed, the dose is not replenished, and the subsequent dose is not doubled.
It is necessary to delay the vaccination schedule (not earlier than 3 months or even 1 year after the end of the last course of chemotherapy) to the patient and other family members living with him (oral immunization against poliomyelitis should be discarded). Avoid contact with infectious patients or use non-specific measures for prevention (protective mask, etc.).
It should be refrained from using in pediatric practice, since safety and effectiveness of its use in children are not defined.Adequate contraceptive measures should be used during treatment.
In case of contact with the skin or mucous membranes, thorough rinsing with water (mucous membranes) or with soap and water (skin) is necessary.