Lomustine, which is a derivative of nitrosourea, is a crystalline powdered substance of light cream color. Being thermally unstable, it easily decomposes during melting.
Virtually unresolvable in water, lomustine is perfectly soluble in absolute( no impurities) ethyl alcohol and its 10% solution, as well as in dimethylformamide, acetone and dimethylsulfoxide.
Form release, composition and packaging
The preparation is available in the form of hard gelatin capsules of light blue color.
The capsule body is made from a composition of auxiliary substances: gelatin, lactose, titanium dioxide, starch, magnesium stearate and talc.
There are two packaging options:
- Some manufacturers pack capsules in vacuum blisters( ten or twenty pieces) of aluminum foil. Blisters( three to ten pieces) and instruction on the use of the drug are put in cardboard packs.
- Other manufacturers prefer to pack capsules in plastic bottles, accommodating twenty pieces. Each bottle( along with the instructions for use) is placed in an individual cardboard package.
- The German pharmaceutical company Medak GmbH is the owner of the registration certificate for lomustine drug. At its own enterprises, all stages of its production are established.
- Pharmaceutical companies of another German company - Haupt Pharma Amareg GmbH - are issuing the drug lomustine.
- In addition, Moldovan pharmaceutical company Balkan Pharmaceuticals is engaged in production of lomustine.
Indications for use
The drug lomustine is indicated for use in the presence of:
- multiple myeloma( diseases of the hematopoiesis);
- disseminated skin melanoma;
- primary or metastatic brain tumors( it is prescribed after radiotherapy and surgical treatment);
- lymphoid tumors( eg, lymphogranulomatosis - Hodgkin's disease) for second-line therapy;
- malignant tumors, localized in the organs of the digestive tract( colon, pharynx, stomach);
- malignant neoplasms of the respiratory system( bronchi, small cell lung cancer).
Lomustine is used for both monotherapy and in combination with other medicines( during combined treatment).
The drug is contraindicated for the treatment of pregnant women, nursing mothers and patients:
- having an increased sensitivity to the active ingredient and the individual components of its chemical composition;
- with severe cancerous cachexia( extreme stage of malnutrition);
- suffering significant impairment of liver and kidney function;
- with obvious myelosuppression( a sharp decrease in the number of platelets and leukocytes in the blood, mainly due to poor kidney function).
Special care should be taken with lomustine in relation to elderly people, patients who have a history of previous radiation therapy and treatment with cytostatic drugs, as well as patients suffering from:
- chicken pox( including recently transferred, dangerousalso contact with a sick person);
- herpes zoster;
- with acute infectious diseases of bacterial, viral or fungal origin;
- respiratory insufficiency.
Mechanism of action
Lomustine belongs to the category of antitumor drugs that have a so-called alkylating action.
Lomustine is able to slow down the course of key enzymatic processes, changing the functions and structure of a number of enzymes and proteins. Its antitumor effect is explained by cytostatic properties-the ability to suppress the division of cancer cells by interfering with the cell cycle process either in G1 stage or in the period of its successive stage.
After oral administration, the drug is absorbed very quickly and practically without residue from the organs of the gastrointestinal tract. The maximum concentration of the drug in the blood plasma is reached within one to four hours. The level of communication with blood proteins is 50%.
Having overcome the blood-brain barrier, the drug penetrates into breast milk and into the cerebrospinal fluid( in it, its concentration is more than half the value achieved in blood plasma).Metabolism( the conversion of the active substance into soluble forms) of lomustine occurs in the structures of the liver. In this case, active metabolites are formed - organic substances isocyanate and oxymethyldiazonium.
The half-life of these substances can last from sixteen hours to two days. The excretion of metabolites of lomustine is carried out mainly by the structures of the kidneys;Only 5% of the decay products leave the body of the patient along with the calves.
Instructions for use Lomustine
- The drug is intended for oral( through the mouth) reception. Take capsules should be either three hours after eating, or before going to night rest.
- Both for adult patients and for children( under condition of normal functioning of bone marrow) the recommended dosage is 130 mg per m2.Capsules are taken once, every six weeks. In some cases, this amount of the drug is divided into three parts and taken for three consecutive days.
- If the bone marrow function is reduced, the amount of the drug is reduced to 100 mg / m2.A six-week pause between medications is maintained.
- With respect to patients with severe cumulative myelosuppression, longer intervals between doses are sometimes tolerated.
- With combined chemotherapy, the dosage of lomustine is reduced to seventy to one hundred mg / m2.
- Another indication for reducing dosage is a low( less than 3000 μL) level of white blood cells and platelets( less than 75,000 per μL) in the blood.
- Since the effect of lomustine leads to a prolonged suppression of bone marrow function, the period required to restore normal platelets and white blood cells can take more than six weeks.
- If the level of leukocytes and platelets continues to be at a critically low level( less than 4000 / μL and 100,000 / μL, respectively), the appointment of repeated courses is prohibited.
- The total dose of the drug received by the patient during all therapeutic courses should be below 1,000 mg / m2.
- The further dosage of lomustine is individually selected depending on how the patient's organism responded to taking the previous dose of the drug. The indicator of this reaction is the characteristics of the hematologic response, which will be shown by blood tests.
Side effects of
Reception of lomustine can lead to a large number of adverse reactions.
- The hematopoiesis of respond to treatment with the development of thrombocytopenia( this happens four weeks after the start of the admission) and leukopenia( five to six weeks after the start of therapy).Thrombocytopenia, as a rule, proceeds more severely. The development of granulocytopenia and anemia is much less frequent.
- Digestive organs respond to chemotherapy with the appearance of nausea and vomiting( this reaction occurs a few hours after taking the drug and can continue for a day), anorexia. To alleviate the condition of the patient can be by prophylactic intake of anti-emetic drugs. Sometimes the reception of lomustine on an empty stomach helps. A small proportion of patients may develop stomatitis and diarrhea, and a high concentration of bilirubin and liver enzymes is found in the blood.
- In response to reception of lomustine, respiratory organs of may respond with the appearance of a cough, the development of respiratory failure, which can lead to pulmonary fibrosis or the appearance of an infiltrate in certain areas of the lung tissue.
- The nervous system of a patient receiving lomustine often reacts with the appearance of articulatory disorders, disorientation in space, increased fatigue, ataxia( coordination of movements) and lethargy( a state of sluggishness and lethargy).
- For the treatment with lomustine, the urinary system reacts with a delay in urine, strong swelling of the legs, a decrease in the volume of the kidneys, development of azotemia( an increase in the amount of nitrogenous metabolic products in the blood, usually excreted by the kidneys).
- The effect of lomustin on the reproductive system of the patient may result in the development of amenorrhea( a prolonged absence of menstruation) and azoospermia( lack of sperm cells ejaculate).Azoospermia can sometimes become irreversible.
- In rare cases, the reception of lomustine can lead to the appearance of alopecia and irreversible damage to the optic nerves of , fraught with the development of complete blindness.
Overdose of lomustine is fraught with a significant increase in the above-listed side effects. The patient can be observed:
- dysfunction of bone marrow hematopoiesis;
- all kinds of disruptions in the work of the digestive system;
- a number of neurological disorders;
- significant deterioration of the liver.
To correct the situation, resort to supportive and symptomatic therapy, take measures to compensate for lost blood components. To date, there is no specific antidote.
- The appointment of lomustine( as well as the control of the treatment process) should be handled only by an experienced specialist.
- A patient receiving lomustine needs weekly monitoring of peripheral blood condition: both during treatment and for six weeks after completion. The same control is necessary for laboratory indicators of liver and kidney function.
- Weakened patients with severe leukopenia and thrombocytopenia often experience bleeding and severe infections.
- Before starting chemotherapy, it is necessary to take into account the state of the lungs, since in the presence of a reduced function of this organ, there is a high risk that lomustine will provoke symptoms of pulmonary toxicity.
- You can not use lomustine more than once in a month and a half.
- Patients of childbearing age( both sexes) should be provided with proven contraceptive methods during the period of chemotherapy.
- Given the irritating effect of fine powder on skin and mucous membranes, it is unacceptable to open capsules with the drug.
- The use of lomustine in combined chemotherapy regimens along with the drug "Cimetidine" and cytostatic drugs( which can lead to the development of myelosuppression in the background of radiotherapy sessions) can significantly increase the occurrence of thrombocytopenia and leukopenia.
- The interaction of drugs lomustine and amphotericin can lead to a nephrotoxic effect( a toxic effect that can lead to severe kidney damage), lower blood pressure and bronchospasm.
- Undesirable simultaneous use of lomustine with the drug "Theophylline", because in medical practice cases of significant increase in their toxicity have been described.
- Metabolism of the drug lomustine can increase under the influence of phenobarbital, which can activate a number of microsomal enzymes.
- The impact of vaccines, which contain living viruses, can significantly weaken the immune system of patients receiving lomustine, resulting in antibodies to pathogens of dangerous diseases will be produced in insufficient quantities. This picture will be observed for a fairly long( from three months to a year) period after completion of chemotherapy. That is why vaccination of such patients with live vaccines must be abandoned.
Survey of patients who have ever taken lomustine, showed that in the overwhelming( more than 80%) of the majority of cases, treatment has yielded positive results.
The therapy with lomustine significantly eased my condition, feeling much better.
I was diagnosed with Hodgkin's disease. Chemotherapy of the first line did not give any result. After that, I was assigned a complex of two cytostatic drugs: lomustine and avastin. Growth of the tumor stopped, the state of health is quite satisfactory. The doctor said that this effect was largely due to lomustine. Very good drug.
I suffer from colon cancer. Chemotherapy with lomustine, although it produced a lot of side effects, showed a positive trend: it was possible to stop the growth of the tumor. Overall well-being is also gradually improving. The result of treatment is satisfied.
Price in Moscow
The cost of the drug in pharmacies in Moscow depends not only on the manufacturer, but on what pharmacy network it is sold in:
Similar drugs have medicines belonging to the same pharmacological subgroup:
In pharmacology, the drug lomustine is known by synonymous names:
- "Lomustin Medak";
Conditions for dispensing from pharmacies
Lomustine can be purchased at the pharmacy after the mandatory presentation of a prescription certified by the stamp of the attending physician.
Storage Conditions and Shelf Life
A drug belonging to List B is stored in a place that excludes free access of children. Storage temperature should not be above twenty-five degrees. Shelf life is 36 months. The drug with expired shelf life is prohibited to be consumed and must be disposed of.