Natulan, 50 mg capsules, 50 pcs.

Pharmacodynamics

Antitumor drug, alkylating compound of methylhydrazine group. The mechanism of action of procarbazine is not accurately studied. The drug inhibits protein, DNA and RNA synthesis by disrupting the processes of transmethylation – transfer of methyl radicals from methionine to transport RNA (tRNA). Lack of normally functioning tRNA causes disruption of DNA, RNA and protein synthesis (refers to S-phase-specific agents). 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 denser spiralization of DNA molecule and hinders the processes of transcription.

Blocks MAO activity, which causes accumulation of tyramine and, as a consequence, increase of noradrenaline in the ends of the sympathetic nervous system and increase of BP.

Pharmacokinetics

Intake and distribution

After oral administration, it is quickly and completely absorbed from the gastrointestinal tract. Cmax is reached within 30-60 min. It penetrates through the HEB.

Metabolism and excretion

Metabolized in the liver and kidneys with the formation of active metabolites. T1/2 is 10 minutes.

Extracted mainly by kidneys (70% is excreted in 24 hours in the urine, mainly as N -isopropylterephthalic acid, less than 5% – unchanged) and lungs as methane and carbon dioxide.

Indications

Active ingredient

Composition

1 capsule contains:

Active ingredients: procarbazine hydrochloride 58.3 mg, including procarbazine 50 mg.

Excipients: starch, talc, magnesium stearate, mannitol.

Capsule shell composition: gelatin, titanium dioxide, iron oxide (E172).

In a bottle of dark glass 50 capsules. In a cardboard package of 1 vial.

How to take, the dosage

Prescribe orally, after meals. When choosing the dose and pattern of administration of the drug in each individual case, reference should be made to special literature.

In monotherapy the initial dose of Natulan is 50 mg with a subsequent daily increase of 50 mg to a daily dose of 250-300 mg. Frequency of administration is 1-3 times/day, daily for 15-20 days or until the development of leukopenia and thrombocytopenia. In case of development of therapeutic effect, the dose is gradually reduced to maintenance dose, usually to 150-50 mg/day. The total dose for a course of treatment is usually 4-7 g.

In combination with other antitumor drugs, Natulan is prescribed at a dose of 100 mg/m2 daily for 10-14 days.

Interaction

The simultaneous use of other myelotoxic drugs and radiation therapy may additive suppression of bone marrow function.

Natulan increases the activity of sympathomimetics, barbiturates, antihistamines, narcotic, hypotensive drugs, tricyclic antidepressants and phenothiazine.

When used concomitantly, Natulan potentiates the effect of hypoglycemic agents and anticonvulsant drugs.

Concomitant use of NSAIDs increases the risk of bleeding.

Natulan is incompatible with ethyl alcohol (possible development of disulfiram-like reaction).

Special Instructions

Treatment with Natulan is carried out under the supervision of a physician experienced in the use of antitumor drugs.

During therapy with procarbazine, close monitoring of hematological (before treatment, then once every 3-4 days) and biochemical (before treatment, then once a week) blood parameters is necessary.

In case of nervous system disorders (paresthesias, peripheral neuropathy, confusion), leukopenia ( < 4000/μl), thrombocytopenia ( < 100 000/μl), allergic reactions, stomatitis, diarrhea, increased bleeding or bleeding should be stopped immediately with Natulan.

The use of alcohol, hypnotics (barbiturates, benzodiazepines) and sympathomimetic agents is contraindicated during treatment. Foods with high tyramine content (aged cheeses, wine, beer, yeast/protein extracts, yogurt, bananas) should be excluded from the diet.

Impact on the ability to drive vehicles and other mechanisms requiring increased concentration

When treating with Natulan, caution should be exercised when driving and engaging in other potentially dangerous activities that require increased concentration and rapid psychomotor reactions.

Contraindications

With caution: the drug should be used in arrhythmias and other cardiovascular diseases, diabetes mellitus, hyperthyroidism, vascular diseases of the brain, paranoid schizophrenia and other conditions accompanied by hyperexcitability, epilepsy, alcoholism, parkinsonism, chicken pox, herpes zoster, other systemic infections, chronic viral diseases, prior cytotoxic or radiation therapy, history of sympathectomy, elderly patients.

Side effects

Hematopoietic system disorders: leukopenia, thrombocytopenia, eosinophilia, hemolytic anemia, bleeding and hemorrhage.

Digestive system disorders: nausea, vomiting, anorexia, dysphagia, dry mouth, diarrhea, constipation, abdominal pain, stomatitis, liver dysfunction, cholestatic jaundice.

CNS and peripheral nervous system disorders: headache, dizziness, paresthesia, peripheral neuropathy, increased excitability, hypomanic and manic states, seizures, hallucinations, depression, nightmares, increased fatigability, confusion, coma, weakness; rarely – ataxia.

Sensory organs: diplopia, nystagmus, photophobia, optic edema, intraocular hemorrhage, impaired hearing.

Cardiovascular system: decreased BP, tachycardia, syncope.

Respiratory system: pneumonitis, pleurisy, cough.

Urinary system disorders: impaired renal function, hematuria, amenorrhea, azoospermia.

Dermatological reactions: dermatitis, skin itching, rash, urticaria, alopecia, hyperpigmentation, feeling of hot flashes or facial redness.

Muscular system disorders: arthralgia, myalgia, tremor.

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

Overdose

Symptoms: nausea, vomiting, enteritis, diarrhea, decreased BP, tremors, seizures, coma, marked suppression of medullary hematopoiesis, liver function abnormality.

Treatment: induction of vomiting or gastric lavage (in the first hour after overdose), symptomatic therapy, monitoring of vital functions (during overdose signs and for at least 2 weeks after the patient’s condition normalizes).

Pregnancy use

The drug is contraindicated in pregnancy and during lactation (breastfeeding).

Men and women of childbearing age should use reliable contraceptive methods during treatment with Natulan and for at least 3 months after.