NATULAN

Active material: Procarbazine
When ATH: L01XB01
CCF: Anticancer drug
ICD-10 codes (testimony): C71, C81, C82, C83, (C) 83.3, Q91.1
When CSF: 22.01.07
Manufacturer: SIGMA-TAU Industrie Pharmaceutical Riunite S.p.A.. (Italy)

Pharmaceutical form, composition and packaging

Capsules hard gelatin, Oval, ivory; contents of capsules – melkogranulirovanny powder white or white with a yellowish tint.

Excipients: starch, talc, magnesium stearate, mannyt.

Ingredients of the capsule shell: gelatin, Titanium dioxide, E172.

50 PC. – vials of dark glass (1) – packs cardboard.

Pharmacological action

Anticancer drug, alkylating a compound from the group of methylhydrazine. procarbazine mechanism of action has not been studied with precision. The drug inhibits protein synthesis, DNA and RNA, disrupting the processes of transmethylation – Transfer of the methyl radicals with methionine at transfer RNA (tRNA). Absence of a normally functioning tRNA causes a disturbance in DNA synthesis, RNA and proteins (It refers to S-fazospetsifichnym Drugs). An important component in the mechanism of action is the generation of hydrogen peroxide as a result autooksigenatsii. Hydrogen peroxide, interacting with sulfhydryl groups of tissue proteins, contributes to a more dense helix DNA molecules and difficulty of transcription.

Blocks the activity of MAO, which causes the accumulation of tyramine, Consequently, increase of noradrenaline in the endings of the sympathetic nervous system and increase blood pressure.

Pharmacokinetics

Absorption

Once inside, quickly and completely absorbed from the digestive tract. C_max It reached within 30-60 m.

Metabolism and excretion

It is metabolized in the liver and kidneys to form the active metabolite. T_1/2 is 10 m.

Report mostly kidneys (70% excreted in the urine for 24 no, mainly in the form of N -izopropiltereftalevoy acid, less 5% – in unchanged form) and light in the form of methane and carbon dioxide.

It penetrates through the BBB.

Testimony

- Hodgkin's disease (limfogranulematoz);

- non-Hodgkin's lymphoma;

- retikulosarkoma;

- Chronic Lymphocytic Leukemia;

- disease Brill-Simmersa;

- Malignant Brain Tumor (neuroblastoma and medulloblastoma).

Dosage regimen

Assign inside, postprandial. When selecting the dose and schemes of the drug in each individual case should be made to the literature.

At monotherapy initial dose is Natulan 50 mg daily, followed by an increase in 50 mg and the daily dose 250-300 mg. Reception frequency – 1-3 times / day, daily for 15-20 days or until the development of leukopenia and thrombocytopenia. With the development of the therapeutic effect of the dose is gradually reduced to a maintenance, typically up to 150-50 mg / day. The total dose per course of treatment, usually, is 4-7 g.

IN combinations with other anticancer drugs administered in a dose Natulan 100 mg / m² daily for 10-14 days.

Side effect

From the hematopoietic system: leukopenia, thrombocytopenia, eozinofilija, gemoliticheskaya anemia, bleeding and hemorrhage.

From the digestive system: nausea, vomiting, anorexia, dysphagia, dry mouth, diarrhea, constipation, abdominal pain, stomatitis, abnormal liver function, cholestatic jaundice.

From the central and peripheral nervous system: headache, dizziness, paraesthesia, perifericheskaya neuropathy, hypererethism, hypomanic and manic states, convulsions, hallucinations, depression, nightmares, fatigue, confusion, coma, weakness; are rarely - ataxia.

From the senses: diplopia, nistagmo, photophobia, swelling of the optic nerve, intraocular hemorrhage, impaired hearing.

Cardio-vascular system: decrease in blood pressure, tachycardia, syncope.

The respiratory system: pneumonitis, pleurisy, cough.

From the urinary system: impairment of renal function, hematuria, amenorrhea, azoospermia.

Dermatological reactions: dermatitis, itching, rash, hives, alopecia, giperpigmentatsiya, feeling hot flushes or redness of the face.

On the part of the musculoskeletal system: arthralgia, myalgia, tremor.

Other: immunosuppression (joining infections), temperature rise, gynecomastia, risk of secondary malignancies, allergic reactions.

Contraindications

- bone marrow hypoplasia;

- expressed human kidney and / or liver;

- Pheochromocytoma;

- Pregnancy;

- Lactation;

- Hypersensitivity to the drug.

FROM caution the drug should be used for arrhythmias and other cardiovascular diseases, diabetes, gipertireoze, vascular diseases of the brain, paranoid schizophrenia and other conditions, accompanied by increased excitability, epilepsy, alcoholism, parkinsonizme, varicella, herpes zoster, other systemic infections, chronic viral diseases, prior cytotoxic or radiation therapy, sympathectomy history, in elderly patients.

Pregnancy and lactation

The drug is contraindicated during pregnancy and lactation (breast-feeding).

The men and women of childbearing age Natulanom during treatment and for at least 3 months should use reliable methods of contraception.

Cautions

Natulanom treatment is carried out under the supervision of a physician, having experience with anticancer drugs.

During therapy, procarbazine careful monitoring of haematological (before treatment, then 1 once every 3-4 day) and biochemical (before treatment, then 1 once a week) blood parameters.

When the disturbances in the nervous system (paresthesia, perifericheskaya neuropathy, confusion), leukopenia (<4000/l), thrombocytopenia (<100 000/l), allergic reactions, stomatitis, diarrhea, increased bleeding or bleeding Natulanom treatment should be stopped immediately.

During treatment contraindicated alcohol, hypnotics (barbiturates, benzodiazepines) and sympathomimetic agents. From the diet should exclude products with a high content of tyramine (aged cheeses, wine, beer, yeast / protein extracts, yogurt, bananas).

Effects on ability to drive vehicles and management mechanisms

During treatment Natulanom must be careful when driving and busy with other potentially hazardous activities, require high concentration and speed of psychomotor reactions.

Overdose

Symptoms: nausea, vomiting, enteritis, diarrhea, decrease in blood pressure, tremor, convulsions, coma, pronounced suppression of bone marrow hematopoiesis, abnormal liver function.

Treatment: induction of vomiting or gastric lavage (in the first hour after overdosing), simptomaticheskaya therapy, monitoring vital functions (while signs of overdose, and for at least 2 weeks after normalization of the patient's condition).

Drug Interactions

With simultaneous use of other drugs and myelotoxicity of radiation therapy may additive inhibition of bone marrow function.

Natulan increases the activity of sympathomimetic, ʙarʙituratov, antihistamines, Narcotic, antihypertensive drugs, tricyclic antidepressants and phenothiazines.

With simultaneous application Natulan potentiates the effect of hypoglycemic drugs and anticonvulsant drugs.

With simultaneous use of NSAIDs increase the risk of bleeding.

Natulan incompatible with ethanol (development disulfiramopodobnyh reaction).

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

A List. The drug should be stored out of reach of children, dry place at temperatures no higher than 25 ° C. Shelf life – 3 year.