Composition, form of production and packaging
Capsules hard gelatinous, oval, ivory; the contents of the capsules are finely granulated white or white powder with a yellowish hue.
1 caps.
procarbazine hydrochloride 58.3 mg,
in t.ch. procarbazine 50 mg
Auxiliary substances: starch, talc, magnesium stearate, mannitol.
The composition of the capsule shell: gelatin, titanium dioxide, iron oxide (E172).
50 pcs. - bottles of dark glass (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
An antineoplastic agent that alkylates a compound from the group of methylhydrazines. The mechanism of action of procarbazine has not been studied with accuracy.The drug inhibits the synthesis of proteins, DNA and RNA, disrupting the processes of transmethylation - the transfer of methyl radicals from methionine to transport RNA (tRNA). The lack of a normally functioning t-RNA causes disruption of the synthesis of DNA, RNA and proteins (refers to S-phase-specific drugs). An important component in the mechanism of action is the formation of hydrogen peroxide as a result of autooxygenation. Hydrogen peroxide, interacting with sulfhydryl groups of tissue proteins, promotes more dense spiralization of the DNA molecule and hinders transcription processes.
It blocks the activity of MAO, which causes accumulation of tyramine and, as a result, an increase in the content of noradrenaline in the endings of the sympathetic nervous system and an increase in blood pressure.
PHARMACOKINETICS
Suction and distribution
After ingestion, quickly and completely absorbed from the digestive tract. C max is reached within 30-60 minutes. Penetrates through the BBB.
Metabolism and excretion
Metabolised in the liver and kidneys with the formation of active metabolites. T 1/2 is 10 minutes.
It is excreted primarily by the kidneys (70% excreted in urine in 24 hours, mainly in the form of N-isopropyl terephthalic acid, less than 5% in unchanged form) and lungs in the form of methane and carbon dioxide.
INDICATIONS
- Hodgkin's disease (lymphogranulomatosis);
- non-Hodgkin's lymphomas;
- reticulosarcoma;
- chronic lymphocytic leukemia;
- Brill-Simmers disease;
- malignant brain tumors (neuroblastoma and medulloblastoma).
DOSING MODE
Assign inside, after eating. When choosing the dose and the scheme of application of the drug in each individual case, you should refer to the special literature.
In monotherapy, the initial dose of Natulan is 50 mg, followed by a daily increase of 50 mg to a daily dose of 250-300 mg. Frequency of admission - 1-3 times / day, daily for 15-20 days or until the development of leukopenia and thrombocytopenia. When the therapeutic effect develops, the dose is gradually reduced to a maintenance dose, usually to 150-50 mg / day. The total dose for the course of treatment, as a rule, is 4-7 g.
In combination with other antitumor drugs, Natulan is administered at a dose of 100 mg / m 2 daily for 10-14 days.
SIDE EFFECT
From the hemopoietic system: leukopenia, thrombocytopenia, eosinophilia, hemolytic anemia, bleeding and hemorrhage.
On the part of the digestive system: nausea, vomiting, anorexia, dysphagia, dry mouth, diarrhea, constipation, abdominal pain, stomatitis, impaired liver function, cholestatic jaundice.
From the side of the central nervous system and peripheral nervous system: headache, dizziness, paresthesia, peripheral neuropathy, increased excitability, hypomaniacal and manic conditions, convulsions, hallucinations, depression, nightmares, fatigue, confusion, coma, weakness; rarely - ataxia.
From the sense organs: diplopia, nystagmus, photophobia, edema of the optic nerve, intraocular hemorrhage, hearing loss.
From the cardiovascular system: lowering blood pressure, tachycardia, syncope.
On the part of the respiratory system: pneumonitis, pleurisy, cough.
From the side of the urinary system: a violation of kidney function, hematuria, amenorrhea, azoospermia.
Dermatological reactions: dermatitis, pruritus, rash, hives, alopecia, hyperpigmentation, hot flushes or reddening of the face.
From the musculoskeletal system: arthralgia, myalgia, tremor.
Other: immunosuppression (attachment of infections), fever, gynecomastia, risk of developing secondary malignant tumors, allergic reactions.
CONTRAINDICATIONS
- bone marrow hypoplasia;
- pronounced impairment of renal and / or liver function;
- pheochromocytoma;
- Pregnancy;
- lactation period;
- Hypersensitivity to the components of the drug.
With caution should be used in patients with arrhythmias and other cardiovascular diseases, diabetes, hyperthyroidism, cerebral vascular diseases, paranoid schizophrenia and other conditions, accompanied by increased excitability, epilepsy, alcoholism, parkinsonism, chicken pox, herpes zoster, other systemic infections, chronic viral diseases, previous cytotoxic or radiotherapy, sympathectomy in history, in elderly patients.
PREGNANCY AND LACTATION
The drug is contraindicated for use in pregnancy and lactation (breastfeeding).
Men and women of childbearing age should be treated with Natulan and at least 3 months after the treatment, reliable methods of contraception should be used.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated in the presence of severe impairment of kidney function.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in severe liver function disorders.
APPLICATION IN ELDERLY PATIENTS
With caution should be used in elderly patients.
SPECIAL INSTRUCTIONS
Natulan treatment is performed under the supervision of a doctor who has experience in the use of antitumor drugs.
During therapy with procarbazine, careful monitoring of hematologic parameters (before treatment, then once every 3-4 days) and biochemical (before treatment, then once a week) blood values ​​is necessary.
When there are disorders of the nervous system (paresthesia, peripheral neuropathy, confusion), leukopenia (<4000 / Ојl), thrombocytopenia (<100,000 / Ојl), allergic reactions, stomatitis, diarrhea, increased bleeding or bleeding, Natulan should be stopped immediately .
During the period of treatment, the use of alcohol, hypnotics (barbiturates, benzodiazepines) and sympathomimetic agents is contraindicated. From the diet should exclude foods with increased content of tyramine (aged cheeses, wine, beer, yeast / protein extracts, yogurt, bananas).
Impact on the ability to drive vehicles and manage mechanisms
During Natulan's treatment, care must be taken when driving a car and engaging in other potentially hazardous activities that require increased attention and speed of psychomotor reactions.
OVERDOSE
Symptoms: nausea, vomiting, enteritis, diarrhea, decreased blood pressure, tremor, convulsions, coma, severe oppression of bone marrow hematopoiesis, impaired liver function.
Treatment: Induction of vomiting or gastric lavage (the first hour after an overdose), symptomatic therapy, monitoring of vital functions (during signs of overdose and for at least 2 weeks after the patient's condition is normalized).
DRUG INTERACTION
With the simultaneous use of other myelotoxic drugs and radiotherapy, additive inhibition of bone marrow function is possible.
Natulan increases the activity of sympathomimetics, barbiturates, antihistamines, narcotic, hypotensive drugs, tricyclic antidepressants and phenothiazine.
With the simultaneous application Natulan potentiates the action of hypoglycemic agents and anticonvulsant drugs.
With the simultaneous use of NSAIDs increase the risk of bleeding.
Natulan is incompatible with ethyl alcohol (development of a disulfiram-like reaction is possible).
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List A. The drug should be stored out of reach of children, dry place at a temperature of no higher than 25 В° C. Shelf life - 3 years.
