Procarbazine
When ATH:
L01XB01
Characteristic.
White or pale yellow crystalline powder. Soluble in water. Aqueous solutions of unstable.
Pharmacological action.
Antitumor, alkylating, cytostatic, immunosuppressive.
Application.
Limfogranulematoz, malignant reticulosis, gistiotsitarnaya lymphoma, Waldenstrom's macroglobulinemia, limfotsitarnaya lymphoma, a disease Brill-Simmers, nehodzhkinskaya lymphoma, primary brain tumor, lung cancer, melanoma, multiple myeloma, polycythemia vera.
Contraindications.
Hypersensitivity, heart failure, renal failure, bone marrow hypoplasia, pheochromocytoma.
Restrictions apply.
Assessment of the risk-benefit ratio is needed in the appointment of the following cases: arrhythmia and other cardiovascular diseases, diabetes, hyperthyroidism, vascular diseases of the brain, severe and frequent headaches, paranoid schizophrenia and other conditions, accompanied by increased excitability, epilepsy, alcoholism, parkinsonizm, enable vetryanaya, herpes zoster and other systemic infections, chronic viral diseases, prior cytotoxic or radiation therapy, sympathectomy history, advanced age.
Pregnancy and breast-feeding.
Contraindicated in pregnancy.
Category actions result in FDA - D. (There is evidence of the risk of adverse effects of drugs on the human fetus, obtained in research or practice, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk, if the drug is needed in life-threatening situations or severe disease, when safer agents should not be used or are ineffective.)
At the time of treatment should stop breastfeeding.
Side effects.
From the digestive tract: anorexia, dysphagia, dry mouth, nausea, vomiting, diarrhea / constipation, abdominal pain, stomatitis, caries and other diseases periodontal tissue, oral candidiasis, liver, cholestatic jaundice, ileus, bleeding.
From the nervous system and sensory organs: headache, paraesthesia, peripheral neuropathy, ataxia (rarely), CNS excitation, hypomanic and manic states, convulsions, hallucinations, nightmares, fatiguability, asthenia, confusion, coma, weakness, fatigue; diplopia, nistagmo, photophobia, swelling of the optic nerve, intraocular hemorrhage, impaired hearing.
Cardio-vascular system and blood (hematopoiesis, hemostasis): hypertensive crisis, orthostatic hypotension, leukopenia, thrombocytopenia, eozinofilija, gemoliticheskaya anemia, bleeding and hemorrhage.
From the side of respiratory system: pneumonitis, pleurisy, cough (rarely).
With the genitourinary system: impairment of renal function, painful and difficult urination, hematuria, amenorrhea, azoospermia.
For the skin: allergic reactions (dermatitis, itch, rash, urticaria and other.), alopecia, giperpigmentatsiya, feeling of warmth or redness of the face, prurigo.
Other: pain syndrome (backache, in hand, muscles and joints), immunosuppression (the development of infections), temperature rise, gynecomastia, the risk of developing malignant tumors.
Cooperation.
To minimize the CNS depression and possible potentiation of caution when combined with barbiturates procarbazine, narkoznami, antihistamines, antihypertensives, fenotiazinami. Procarbazine incompatible with ethanol (possible reaction disulfiramopodobnyh).
Since procarbazine has a weak inhibitory effect on the activity of MAO, you must avoid the use of sympathomimetics (increases kardiostimuliruûŝee and sossoudossouerveshchee effect simpatomimetikov — should not appoint simultaneously and within 2 Weeks after the abolition procarbazine), tricyclic antidepressants (incl. with amitriptyline, imipramine).
Not recommended simultaneous application with carbamazepine, maprotilinom and MAO inhibitors, including furazolidone and pargyline (the interval between the discontinuation of the past and the beginning of the procarbazine therapy should be at least 2 Sun). NSAIDs increase the risk of bleeding.
With the simultaneous use of other drugs myelotoxicity, Radiotherapy possible additive inhibition of bone marrow function.
Weakens the effectiveness of immunization inactivated vaccines; using vaccines, containing live viruses, may enhance viral replication and side effects of vaccination.
Overdose.
Symptoms: minimal for 12 h after dosing, reaches its maximum after 24-48 h (persist for several days) - Nausea, vomiting, dizziness, hallucinations, depression, convulsions, hypotension, tachycardia, severe bone marrow depression, fever, bleeding.
Treatment: induction of vomiting or gastric lavage followed by administration of activated charcoal suspension (when the first symptoms), simptomaticheskaya therapy, monitoring vital functions, of mechanical ventilation, oxygen therapy, slow in / diazepam (if signs of CNS stimulation), in / in a dilute solution of vasoconstrictor drugs (with hypotension and circulatory collapse), relief of symptoms hypermetabolic state. The PNDS krizah-discontinuation of procarbazina, in/in the slow introduction fentolamina dose 5 mg (for immediate reduction of blood pressure), decrease in body temperature by external cooling. If necessary transfusion of blood, the appointment of broad-spectrum antibiotics.
Dosing and Administration.
Inside. Dose picked individually, is corrected on the basis of clinical effect, the severity of the toxic effect.
Adults: on 2-4 mg/kg/day one or divided into several events during the first week of. Later transferred to the dose at the rate of 4-6 mg/kg and conducting therapy before signs of saturation-the emergence of radiation (4In the treatment of severe infections in patients with a normal white blood cell count in adults - at a dose9/l) thrombocytopenia and (100In the treatment of severe infections in patients with a normal white blood cell count in adults - at a dose9/l ), then appoint supportive dose at the rate of 1-2 mg/kg/day.
Babies: by 50 mg a day for 1 Sun, further 100 mg / m2 before signs of saturation; maintenance dose 50 mg / day.
Precautions.
Use only under medical supervision, with experience chemotherapy. Prior to and during treatment (at short intervals) necessary to determine hemoglobin or hematocrit, the number of leukocytes (overall, differential), Platelet, IS aktivnosti, GOLD, LDH, creatinine, Glucose (patients with diabetes), bilirubin and urea nitrogen, and a study of bone marrow.
The dose should be reduced in combination or radiotherapy, old age.
If you experience an allergic reaction, diarrhea, severe leukopenia, thrombocytopenia (the lowest possible level is observed in 4 Sun, restored after about 6 Sun), stomatitis treatment should be discontinued.
Patients, previously treated with cytotoxic drugs, or treated with radiation therapy (in order to avoid the risk of increasing the toxic effect on bone marrow), procarbazine treatment may be no earlier than 1 Months. When the planned abolition of spinal anesthesia is recommended procarbazine at least 10 days prior to surgery.
In the event of thrombocytopenia advised extreme caution when performing invasive procedures, Regular inspection of places on / in the, skin and mucous membranes (for signs of bleeding), limit frequency troublesome and the rejection of the / m injection, control of blood in the urine, vomit, Kale. The patients must be carefully shave, manicure, brush your teeth, dentists use threads and toothpicks; should be the prevention of constipation, avoid falls and other injuries, as well as the intake of alcohol and acetylsalicylic acid, increase the risk of gastrointestinal bleeding.
In the case of expression gematotoksichnosti subsequent treatment possible, если количество лейкоцитов не менее 3·109/л и тромбоцитов более 80·109/l. Should defer vaccination schedule (carried out not earlier than 3 Months before 1 years after completion of the last cycle of chemotherapy) patient and other family members, residing with him (should abandon immunization oral polio vaccine). Avoid contact with infectious patients, or use non-event for the prevention of (face mask, etc.).
During treatment contraindicated alcohol, hypnotics (barbiturates, benzodiazepines) and other symptomatic drugs without a prescription. Be wary of during the drivers of vehicles and people, skills relate to the high concentration of attention. During treatment should use appropriate contraceptive measures. Excluded from the diet products, tyramine-rich or other amines with high vasoconstrictor activity (ripe cheese; beer, incl. low-alcohol or alcohol-free; wine-red and white, shyerri, liqueurs; yeast / protein extracts, yogurt, bananas, beans or green beans, meat and other products), caffeine (chocolate, coffee), car, tea and other tonics.
In case of contact with skin or mucous membranes must be thorough washing with water (mucosa) or soap and water (skin).
