TEMOZOLOMID (Temozolomide)

     Synonym : Temodal, Temodal

     Chemical name : 3,4-methyl Digidro-3- oksoimidazo [5,1-d] -1,2,3,5 - tetrazin-8- karboksamid

     Pharmacology : drugs, anticancer effect, alkiliruyuschee, immunodepressivnoe.

In systemic blood flow in the physiological pH values are rapidly becoming a chemical tsitotoksichny monometiltriazenoimidazolkarboksamid (MTIK). Cytotoxic effect MTIK due alkylation guanina in regulation G6 and N7 (more), followed by the launch of methyl aberrantnogo restore balance. Violate the structure and synthesis of DNA, the cell cycle.

When ingestion rapidly and completely absorbed from the digestive tract. Cmax achieved through 0,5-1,5 hour (the earliest-20 minutes), eating Cmax decreased by 33%, AUC by 9%. Weak links with the blood protein (10-20%). Passes through GEB, enters the spinal fluid. It is metabolized in the liver. T1 / 2 of plasma-1.8 hours Clearance, volume of distribution and T1 / 2 is not dependent on the dose. The plasma clearance is not dependent on age, kidney function, smoking. Write mainly kidneys, 5-10%, unchanged, the rest in the form of 4-amino? 5-imidazol- karboksamida hydrochloride and unidentified polar metabolites.

The children AUC greater than in adults. However, the maximum dose varied one cycle of treatment in children and adults the same, at 1000 mg / m 2. Against Violations of liver function light or medium gravity pharmacokinetic parameters are changed.

In pre-studies on rats and rabbits that received a dose of 150 mg / m 2, was toxic and teratogenic effects on the fetus.

     Application : Malignant glioma (multiformnaya glioblastoma, anaplasticheskaya astrotsitoma) with relapse or progression of the disease after standard therapy; Metastaziruyuschaya common malignant melanoma (1 line therapy).

     Contraindications : Giperchuvstvitelnost, incl. to dakarbazinu expressed mielosupressiya, pregnancy, breast-feeding.

     Restrictions apply to : Age 3 years multiformnoy glioblastome and up to 18 years in malignant melanoma (the effectiveness and safety of not identified).

     Application of pregnancy and breastfeeding : Protivopokazano of pregnancy (no clinical experience), as appropriate destination should warn patients of the possible risks to the foetus. At the time of treatment should stop breast-feeding (data on the penetration of breast milk is not available).

     Side Effects : From the nervous system and sensory organs : the increased fatigability (22%), headache (14%), drowsiness (6%), 2-5% - fatigue, nausea, dizziness, paresteziya breach of taste.

From the cardiovascular system and blood (blood, hemostasis) : thrombocytopenia (19%) and neutropenia (17%) 3 or 4 degrees in patients with gliomoy (with hospitalization and / or cancellation of therapy in 8% and 4% of cases) in patients with melanoma, 20% and 22%, respectively (with hospitalization and / or cancellation of therapy in 3% and 1.3% of cases), a reversible mielosupressiya (in the first cycle of treatment, with a maximum between 21 and 28 days).

For part of the digestive tract : nausea (43%) and vomiting (36%), medium or low degree of gravity (not more than five attacks per day vomiting), severe nausea and vomiting (4%), constipation (17%), anorexia (11 %), diarrhea (8%) 2-5% neuralgia.

Allergic reactions : rash (6%), 2-5% - itch.

Other : fever (6%), 2-5% - syndrome, including abdominal pain, dizziness, vomiting, Alopecia, the reduction of body weight.

     Networking : The simultaneous reception of oppressive bone marrow, increases the likelihood mielosupressii. Valproic acid lowers temozolomida clearance.

     Overdosing : Symptoms : neutropenia, thrombocytopenia (admission to the occasional dose of 1000 mg / m 2 and more).

Treatment : maintenance therapy.

     Dosing and Administration : inside, shock, not less than one hour before meals; Capsules swallow whole, squeezed glass of water. Adults and children older than 3 years old, had not previously been subjected to chemotherapy : initial dose of 200 mg / m 2 1 times a day for 5 consecutive days in the 28-day treatment cycle. For patients previously held chemotherapy, the initial dose of 150 mg / m 2, then increased in the second round to 200 mg / m 2 (if one day the next round of neutrophiles not less than 1.5 · 109 / l and the number of platelets higher than 100.109 / l). The course continues until progression of disease (maximum two years).

     Precautions : Use only by a physician with experience chemotherapy. Treatment started, if not less than 1.5 neutrophiles · 109 / L, platelets least 100.109 / l. Required clinical blood tests before and during therapy : a 22-day, ie a 21-day after the first dose (but not later than 48 hours after the day), and further one week, until the number reaches 1.5 neutrophiles · 109 / l and the number of platelets - 100.109 / l. At number neutrophiles less than 1.0 · 109 / l or platelets less than 50.109 / l in any cycle of treatment needed dose reduction for the next round (the minimum recommended dose of 100 mg / m 2).

Women of childbearing age and men during treatment and during the 6 months after the effective to use contraceptives. Men are encouraged to seek advice about preserving sperm before treatment because of the possible risk of irreversible infertility.

To apply caution in patients older than 70 years (increased risk of stoichiometric and thrombocytopenia), and in patients with the expressed as a violation of liver and kidney. If your powder from the damaged capsule on the skin or mucous membranes should be immediately and thoroughly washed with water. Experience in application gliome for children older than 3 years of age is limited.

To use caution during the drivers of vehicles and people, professions related to high concentration.

     Special instructions : Antiemetiki taken before or after receiving temozolomida. If there is vomiting (5 more attacks during the day 1) to a preliminary antiemeticheskoy therapy.

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