Natulan

Natulan is an antineoplastic medicine from the group of methylhydrazines.

[1], [2], [3], [4], [5], [6]

Indications of the natulana

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

[7],

Release form

Release of the medicine is made in capsules, 50 pieces inside a glass bottle. In the box there is one such bottle.

Pharmacodynamics

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

An important element in the processes of medicamental exposure is the formation of the H2O2 substance, which occurs as a result of self-oxidation. This component interacts with the sulfhydryl categories of proteins that live in tissues. This helps to tighten the spiral of the DNA molecule, and in addition to complicating the transcription processes.

Pharmacokinetics

Element procarbazin is fully and quickly absorbed inside the gastrointestinal tract. With oral administration of drugs, the substance passes through the BBB, quickly reaching equilibrium between levels of fluid and plasma. Peak values after oral use are noted for 60 minutes.

Metabolism of the substance procarbazine flows inside the kidneys with the liver; the process consists of 4 stages: oxidation, and then isomerization and hydrolysis, after which again there is an oxidation, as a result of which the product of metabolism - N-isopropylterephthalic acid is formed.

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

[8]

Dosing and administration

The drug is used orally after eating.

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

• The first day - the intake of 50 mg;
• 2nd day - consumption of 0.1 g;
• 3rd day - intake of 0.15 mg;
• 4th day - application of 0.2 g;
• 5th day - the use of 0.25 g;
• 6th and further days - intake of 0.25-0.3 g.

Continuation of therapy.

Therapy with taking a portion of 0.25-0.3 g / day should be continued until the maximum remission of the disease is achieved. Further it is required to carry out maintenance treatment with taking 50-150 mg of medicine per day.

Therapy can not be stopped until a common course dose of at least 6 g is reached, because before this limit it is difficult to assess the results of remission. If at the initial stage of treatment the white cell count decreases 3000 units, and the platelet counts to 80,000, the use of drugs should be temporarily stopped. Accepting maintenance portions can be resumed when the parameters of the above elements again increase. Because of this, it is extremely important to constantly undergo tests to determine the state of the blood.

Complex treatment.

In the case of cytostatic schemes, 0.1 g / m ² LS are taken per day for 10-14 days. For adults, use once-only 2-4 mg / kg / day or divide the portion into several separate doses and consume during the first 7 days. After this, it is required to switch to a dose, which is calculated according to the scheme of 4-6 mg / kg / day, and to treat until the symptoms of saturation develop (the occurrence of thrombocyto and leukopenia). Next, the drug is taken in a maintenance dose, calculated as 1-2 mg / kg / day.

[10], [11]

Use of the natulana during pregnancy

It is contraindicated to prescribe Natulan to pregnant women. Reproductive age women need to use reliable contraception during the application of this medication.

Patients treated with medication should refuse breastfeeding.

Contraindications

Among the contraindications:

• the presence of high sensitivity with respect to the drug and its constituent elements;
• leuko- or thrombocytopenia in severe degree;
• problems with hepatic or renal activity, having a pronounced character.

Side effects of the natulana

At the stage of the first days of therapy, nausea and loss of appetite were often noted, but these manifestations always passed after a while.

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

• violations of blood and lymph: suppression of bone marrow function, thrombocyto-, pancito- or leukopenia, eosinophilia and anemia (sometimes its hemolytic form);
• problems with the work of the digestive tract: vomiting, constipation, abdominal pain, nausea, diarrhea, stomatitis and anorexia;
• dysfunction of the NS: neuropathy, headaches, paresthesia and convulsions;
• mental disorders: a state of depression, psychosis, a feeling of drowsiness or confusion, as well as hallucinations;
• disorders of the hepatobiliary system: hepatitis, hepatic pathology and jaundice;
• lesions affecting the respiratory system: interstitial pneumonia;
• disorders of vascular activity: the appearance 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;
• disorders of metabolic processes: the development of anorexia;
• problems affecting the reproductive function: prolonged azoospermia;
• neoplasia: non-lymphoid secondary neoplasia, including bronchogenic carcinoma and acute myelocytic leukemia. Myelodysplasia also develops;
• visual disturbances: problems with vision;
• lesions affecting tissues, muscles and skeleton: bone or ligament necrosis and myalgia;
• infectious disorders: sepsis or infection of an intercurrent nature;
• general disorders: asthenia or pyrexia.

[9]

Overdose

Among the signs of intoxication: diarrhea, dizziness, tachycardia, nausea, convulsions, tremors and vomiting, and in addition to hallucinations, increased blood pressure and depression.

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

Interactions with other drugs

For the period of therapy it is required to refuse from the use of alcoholic beverages (in connection with the possibility of development of disulfiram-like symptoms).

Procarbazine is a weak MAOI, so for the time of its use it is necessary to exclude foods containing a large amount of tyramine (among them cheese) from its diet, and besides this it is impossible to take separate medications with it. It is required to abandon the combination of Natulan anti-edema drugs and sympathomimetics.

Since the medicinal effect of Natulan can increase, with it, together with caution and in small portions, it is necessary to take such drugs: inhibitors with a central effect (for example, barbiturates and anesthetics, and in addition opiates), drugs with anticholinergic properties (among them tricyclics), phenothiazine and hypotensive drugs.

[12], [13]

Storage conditions

Natulan should be kept in a dry place inaccessible to small children. Temperatures are not higher than 25 ° C.

[14]

Shelf life

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

Application for children

Children of any age the drug is administered in a dosage of 0.1 g / m ²  (for 2-3 uses).

[15]

Analogues

The analog of the therapeutic agent is Procarbazine.