Purinethol
Purinethol
Purinethol (Mercaptopurine)Pharmacological action
The antitumoral agent, concerns group of antimetabolites, is sulfhydryl analogue of the purine basis of a hypoxanthine.
Mercaptopurinum - the inactive precursor gets cytotoxic properties only after capture by cells and an intracellular metabolism to nucleotides tioguanine.
Indications
- An acute leukosis (as a part of the program of an induction of remission acute leukoses, especially for a maintenance therapy);
- A myelosis.
Dosage regimen
For adults and children the standard dose makes 2.5 mg/kg/sut, or 50-75 mg/m2/days the Dose and duration of treatment define depending on what cytotoxic agents and in what doses are prescribed simultaneously with Purinethol.
Purinethol apply as a part of various schemes of chemotherapy of acute leukoses; more detailed information can be found in the corresponding literature.
At simultaneous application of Purinethol it is necessary to prescribe in a dose making 1/4 from standard.
Not used tablets should be destroyed according to rules of recycling dangerous and toxicants.
Side effect
From hemopoiesis system: oppression of a medullar hemopoiesis with development lejko - and thrombocytopenias.
From the alimentary system: hepatotoxic action; are possible - appetite depression, a nausea, vomiting, a canker of a mucosa of an oral cavity; seldom - an intestine canker.
Allergic reactions: seldom - a medicinal fever, a dermal eruption.
The other: at application of Mercaptopurinum for treatment of inflammatory disease of an intestine the pancreatitis case (the given indication to preparation application is not registered) is described.
Contraindications
- A hypersensibility to any component of a preparation.
Considering gravity of indications to Purinethol application, absolute contraindications to its appointment are not present.
Pregnancy and lactemia
It is necessary to avoid whenever possible Purinethol appointment at pregnancy, especially in I trimester. In each separate case it is necessary to estimate expected advantage of therapy for mother and potential risk for a foetus.
At the pregnant women accepting Mercaptopurinum, healthy children were born, at the same time cases of spontaneous abortions, premature birth and various disturbances at a foetus are described. At the patient with a leukosis, accepting Mercaptopurinum in a dose of 100 mg/sut during all pregnancy (in a combination to a lien irradiation), the normal not full-term child was born.
Purinethol influence on a fecundity at the person is studied insufficiently, but there are reports on a birth of children for men and the women accepting Mercaptopurinum in the childhood or in the teenage period. The transient expressed oligospermatism was observed at the young man accepting Mercaptopurinum in a dose of 150 mg/24h in a combination to Prednisolonum in a dose of 80 mg/24h concerning an acute leukosis.
As well as at treatment by any cytotoxic preparations, at reception Purinethol by any of partners it is necessary to take measures on a contraception.
To the women Purinethol accepting, is not recommended to nurse the child.
In experimental researches it is shown, that Purinethol is toxic an effect has on a foetus at rats at introduction in doses, not toxic for mother; causes destruction of a foetus at introduction in high doses in first half of pregnancy.
Special indicatings
Purinethol treatment should be spent only under the control of the doctor having experience of application of similar preparations.
After the termination of treatment the quantity of leucocytes and thrombocytes continues to decrease, therefore at first signs of too sharp reduction of their number it is necessary to stop preparation reception immediately.
Mercaptopurinum has hepatotoxic an effect at animals and the person. At histological research at the person taped a necrosis of a renal tissue and a bile stasis. It can be observed at preparation application in any dose, but more often at a dose exceeding recommended (2.5 mg/kg/24h, or 75 mg/m2/24h). The control of indicators of function of a liver allows to tap hepatotoxic signs in due time. Changes from a liver are usually reversible at timely cancellation of a preparation though the serious lesion of a liver with a lethal outcome was observed.
Patients should be warned about necessity of Purinethol cancellation at icterus occurrence.
During a remission induction when there is a fast destruction of cells and development of a hyperuricemia/hyperuricosuria and an urate nephropathy is possible, it is necessary to supervise level of urinary acid in blood and urine.
Mercaptopurinum dose decline can be demanded at its simultaneous appointment with the preparations oppressing function of an osteal brain.
The augmentation of number of chromosomal aberrations in lymphocytes of peripheric blood was observed at patients with a leukosis, at the patient with a hypernephroma, accepting Mercaptopurinum in not specified dose, and at patients with chronic diseases of the kidneys accepting a preparation in a dose of 0 mg/kg/days
It has been described two cases of development of an acute myeloleukemia at the patients accepting Mercaptopurinum in a combination with other preparations concerning not tumoral diseases.
The case of development in the patient of a myelosis in 12.5 years after therapy by Mercaptopurinum concerning a myasthenia is described.
Correction of a dose of Mercaptopurinum can be demanded from patients with renal or hepatic insufficiency.
The control of laboratory indicators
At application of a preparation for a remission induction it is necessary to carry out the daily analysis of blood, the regular control of level of urinary acid in blood and urine.
In treatment it is necessary to supervise indicators of function of a liver weekly. More frequent monitoring is recommended at patients with a pathology of a liver and the patients receiving other hepatotoxic preparations.
Overdosage
Symptoms: seldom - the nausea, a diarrhoeia, appetite depression, the basic toxic effect is suppression of a medullar hemopoiesis. Changes from blood are usually more expressed at a chronic overdosage of a preparation, than at unitary Purinethol reception. Disturbance of function of a liver and a gastroenteritis can become perceptible. The risk of an overdosage raises at simultaneous application of Allopyrinolum.
Treatment: active treatment it is not required. Antidotes are unknown, the careful control of analyses of blood, and if necessary - carrying out of symptomatic therapy (including transfusions of components of blood) therefore is recommended.
Conditions and periods of storage
The preparation should be stored in the place dry and protected from light at temperature not above 25 C. The Period of validity - 5 years.
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