Natulan

Natulan is an antineoplastic drug from the methylhydrazine group.

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Indications Natulana

It is used in the treatment of lymphogranulomatosis, lymphosarcoma, reticulosarcoma, and also macrofollicular lymphoblastoma.

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Release form

The medicine is released in capsules, 50 pieces in a glass bottle. There is 1 such bottle in a box.

Pharmacodynamics

The exact pattern of medicinal action of procarbazine has not yet been studied. The drug slows down protein binding, as well as DNA and RNA synthesis, destroying transmethylation processes - the movement of propellant radicals that are transferred from methionine to the tRNA region. In the absence of normally functioning tRNA, the processes of binding proteins and DNA to RNA are disrupted.

An important element of the processes of medicinal action is the formation of the substance H2O2, which occurs as a result of autooxidation. This component interacts with sulfhydryl categories of proteins living in tissues. This contributes to the compaction of the DNA molecule spiralization, and in addition to this, the complication of transcription processes.

Pharmacokinetics

The element procarbazine is fully and quickly absorbed inside the gastrointestinal tract. When administered orally, the drug passes through the BBB, quickly reaching equilibrium values between the levels of liquid and plasma. Peak values after oral use are noted within 60 minutes.

The metabolism of the substance procarbazine occurs in the kidneys and liver; the process consists of 4 stages: oxidation, then isomerization and hydrolysis, after which oxidation occurs again, resulting in the formation of a metabolic product - N-isopropyl terephthalic acid.

The half-life of the component is about 10 minutes. Approximately 70% of the substance is excreted in the urine within 24 hours.

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Dosing and administration

The drug is taken orally, after meals.

Therapy begins with a small dosage, which is then gradually increased to the maximum value of 0.25-0.3 g/day:

• Day 1 – take 50 mg;
• 2nd day – use 0.1 g;
• Day 3 – take 0.15 mg;
• 4th day – use 0.2 g;
• Day 5 - use 0.25 g;
• 6th and subsequent days – take 0.25-0.3 g.

Continuation of therapy.

Therapy with a dose of 0.25-0.3 g/day should be continued until the most complete remission of the disease is achieved. Then, maintenance treatment with a daily dose of 50-150 mg of the drug is required.

Therapy should not be stopped until the total course dose of at least 6 g is reached, because it is difficult to assess the results of remission before this limit. If at the initial stage of treatment the white blood cell count decreases to 3000 units and the platelet count to 80000, the use of the drug should be temporarily stopped. Maintenance doses can be resumed when the counts of the above elements increase again. For this reason, it is extremely important to undergo regular examinations to determine the state of the blood.

Complex treatment.

For cytostatic regimens, 0.1 g/m2 of the drug is taken per day ^for 10-14 days. For adults, take 2-4 mg/kg/day once or divide the dose into several separate doses and take it for the first 7 days. After that, it is necessary to switch to a dose calculated according to the scheme of 4-6 mg/kg/day, and conduct treatment until the development of saturation symptoms (the occurrence of thrombocytopenia and leukopenia). Then the drug is taken in a maintenance dose, calculated according to the scheme of 1-2 mg/kg/day.

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Use Natulana during pregnancy

Prescribing Natulan to pregnant women is contraindicated. Women of reproductive age must use reliable contraception while taking this medication.

Patients being treated with the drug must refrain from breastfeeding.

Contraindications

Among the contraindications:

• the presence of high sensitivity to the drug and its components;
• severe leukopenia or thrombocytopenia;
• problems with liver or kidney function that are severe.

Side effects Natulana

During the first days of therapy, nausea and loss of appetite were often observed, but these symptoms always passed after some time.

The use of the drug also causes the development of the following side effects:

• disorders of blood and lymph functions: suppression of bone marrow function, thrombocyto-, pancyto- or leukopenia, eosinophilia and anemia (sometimes its hemolytic form);
• problems with the gastrointestinal tract: vomiting, constipation, abdominal pain, nausea, diarrhea, stomatitis and anorexia;
• dysfunction of the nervous system: neuropathy, headaches, paresthesia and convulsions;
• mental disorders: depression, psychosis, feeling sleepy or confused, and hallucinations;
• disorders of the hepatobiliary system: hepatitis, liver pathologies and jaundice;
• lesions affecting the respiratory system: interstitial pneumonia;
• vascular disorders: occurrence of bleeding;
• lesions of subcutaneous tissues and epidermis: alopecia, rashes, urticaria, TEN and Stevens-Johnson syndrome;
• immune disorders: signs of allergy, including Quincke's edema and anaphylaxis;
• metabolic disorders: development of anorexia;
• problems affecting reproductive function: prolonged azoospermia;
• neoplasia: non-lymphoid neoplasia of secondary origin, including bronchogenic cancer and acute myelocytic leukemia. Myelodysplasia also develops;
• visual impairment: problems with vision;
• lesions affecting tissues, muscles and skeleton: bone or ligament necrosis and myalgia;
• infectious disorders: sepsis or intercurrent infections;
• General disorders: asthenia or pyrexia.

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Overdose

Signs of intoxication include: diarrhea, dizziness, tachycardia, nausea, convulsions, tremors and vomiting, as well as hallucinations, increased blood pressure and depression.

To eliminate the disorders, it is necessary to induce vomiting or gastric lavage, and then perform intravenous rehydration procedures. The blood condition and liver function should be monitored for 14 days after the patient's condition has stabilized. In addition, antimicrobial prophylaxis is carried out.

Interactions with other drugs

During therapy, it is necessary to refrain from drinking alcoholic beverages (due to the possibility of developing disulfiram-like symptoms).

Procarbazine is a weak MAOI, so for the duration of its use, you should exclude from your diet foods that contain a large amount of tyramine (cheese is one of them), and in addition, you cannot take certain medications with it. You must refuse the combination of Natulan with decongestants and sympathomimetics.

Since the medicinal effect of Natulan may increase, it is necessary to take the following drugs with caution and in small doses: inhibitors with central action (for example, barbiturates and anesthetics, as well as opiates), drugs with anticholinergic properties (including tricyclics), phenothiazine and antihypertensive drugs.

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Storage conditions

Natulan must be kept in a dry place, out of reach of small children. Temperature indicators – no higher than 25°C.

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Shelf life

Natulan can be used for 3 years from the date of release of the drug.

Application for children

For children of any age, the drug is administered in a dosage of 0.1 g/ ^m2 (in 2-3 doses).

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Analogues

An analogue of the therapeutic agent is Procarbazine.