Temtsital

General characteristics. Structure:

Active ingredient: 20 mg, 100 mg, 140 mg, 180 mg or 250 mg of a temozolomid.

Excipients: Mannitolum, carboxymethylstarch of sodium, silicon dioxide colloid, tartaric acid, stearic acid.

Structure of a cover of the capsule: gelatin, titanium dioxide.

Pharmacological properties:

Pharmacodynamics. The antineoplastic, triazine, alkylating drug. Temozolomid at hit in a system blood stream, at physiological values рН is exposed to bystry chemical transformation with formation of active connection - a monometiltriazenoimidazolkarboksamid (MTIK). It is considered that cytotoxicity of MTIK is caused first of all by alkylation of guanine in situation O6 and additional alkylation in situation N7. Apparently, the cytotoxic damages arising thereof include (start) the mechanism of aberrant recovery of the methyl rest.

Pharmacokinetics. After intake темозоломид it is quickly soaked up and also quickly brought out of an organism with urine. Temozolomid quickly gets through a blood-brain barrier and gets to cerebrospinal fluid. Cmax in plasma is reached on average in 0.5-1.5 h (the earliest - in 20 min.) after administration of drug. T1/2 makes about 1.8 h of plasma. The clearance, Vd in plasma and T1/2 do not depend on a dose. Temozolomid poorly contacts proteins of a blood plasma (10-20%).

After oral administration average extent of removal with excrements within 7 days made 0.8% that demonstrates full absorption of drug. The main way of removal - through kidneys. By 24 h after oral administration about 5-10% of a dose is defined in not changed look in urine; other part is removed in a look a 4-amino-5-imidazole-karboksamida of a hydrochloride (AIK) or not identified polar metabolites. Reception of a temozolomid together with food causes decrease in Cmax by 33% and reduction of AUC by 9%.

The clearance of drug in plasma does not depend on age, function of kidneys or consumption of tobacco. A pharmacokinetic profile of drug at patients with an abnormal liver function of weak or moderate degree same, as at persons with normal function of a liver. At children the indicator of AUC is higher, than at adults. The Maximum Tolerable Dose (MTD) at children and adults was identical and made 1000 mg/sq.m on 1 cycle of treatment.

Indications to use:

- for the first time the revealed multiformny glioblastoma – the combined treatment with radiation therapy with the subsequent adjuvant monotherapy.
- a malignant glioma (a multiformny glioblastoma or an anaplastic astrocytoma), in the presence of a recurrence or progressing of a disease after standard therapy.
- the widespread metastasizing malignant melanoma – as therapeutic means of the first row.

Route of administration and doses:

Temtsital ® accept inside, on an empty stomach, not less than in one hour prior to meal. The appointed dose has to be accepted with use of minimum possible number of capsules. Capsules cannot be opened or chewed, and it is necessary to swallow entirely, washing down with a glass of water.

Features of use:

Before the combined treatment (with radiation therapy) performing preventive antiemetic therapy is recommended and it is strongly recommended during adjuvant therapy for the first time of the revealed multiformny glioblastoma. If against the background of treatment nausea arises the drug Temtsital® or vomiting at the subsequent receptions is recommended to carry out antiemetic therapy. Antiemetic drugs can be accepted both to, and after administration of drug of Temtsital®. Even if vomiting developed in the first 2 h after administration of drug of Temtsital®, it is not necessary to repeat administration of drug on the same day.

Due to the increased risk of development of the pneumonia caused by Pneumocystis carinii at the patients receiving the combined treatment with radiation therapy within 42 days (up to 49 days), performing preventive treatment against the Pneumocystis carinii activator is recommended to such patients. Though more frequent development of the pneumonia caused by Pneumocystis carinii is associated with more long terms of treatment by the drug Temtsital®, the increased vigilance concerning possible development of pneumocystic pneumonia should be shown concerning all patients receiving the drug Temtsital®, especially in combination with GKS.

Pharmacokinetic indicators of the drug Temtsital® at persons with normal function of a liver and at patients with an abnormal liver function of weak or moderate severity, are comparable. Data on use of the drug Temtsital® for patients with the expressed abnormal liver function (a class C on classification of Chaylda-Pyyu) or a renal failure are not available. On the basis of data of studying of pharmacokinetic properties of the drug Temtsital® it is represented improbable that even with the expressed abnormal liver function or kidneys the drug dose decline can be required by patients, nevertheless at purpose of the drug Temtsital® such patients should show care.

Men and women of childbearing age during treatment by the drug Temtsital® and at least within 6 months after the termination have to use reliable methods of contraception.

Because of risk of development of irreversible infertility, against the background of treatment by the drug Temtsital®, male patients before an initiation of treatment are in case of need recommended to discuss a possibility of a cryopreservation of sperm.

At hit of contents of the capsule (powder) on skin or mucous membranes they need to be washed out a large amount of water.

Influence on ability to driving of motor transport and to control of mechanisms. During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

The most often observed side effects: rash, itch, alopecia, petechias; nausea, vomiting, lock, anorexia; headache; thrombocytopenia, neutropenia, lymphopenia; increased fatigue; increased fatigue.

Other often observed undesirable phenomena: diarrhea, abdominal pain, dyspepsia, food faddism; drowsiness, dizziness, paresthesias, adynamy. decrease in body weight, asthma, fervescence, fever, febricula.

Seldom observed side effects: small tortoiseshell, dieback, erythrosis, multiformny erythema, toxic epidermal necrolysis, Stephens-Johnson's syndrome; opportunistic infections, including the pneumonia caused by Pneumocystis carinii; pancytopenia, leukopenia, anemia.

Development of a miyelodisplastichesky syndrome (MDS) and secondary malignant processes, including leukemia was very seldom noted, and also development of a long pancytopenia with risk of development of aplastic anemia was noted; allergic reactions, including an anaphylaxis were very seldom observed.

Interaction with other medicines:

Reception of a temozolomid together with ranitidine does not lead to clinically significant change of extent of absorption of a temozolomid.

Joint reception with dexamethasone, prochlorperazine, Phenytoinum, carbamazepine, ondansetrony, blockers of histamine H2 receptors or phenobarbital does not change clearance of a temozolomid.

Joint reception with valproic acid involves poorly expressed, but statistically significant decrease in clearance of a temozolomid.

The researches directed to clarification of impact of a temozolomid on metabolism and removal of other drugs were not conducted.

Because темозоломид it is not metabolized in a liver and poorly contacts proteins of plasma, its action on pharmacokinetics of other medicines is improbable.

Use of a temozolomid together with other substances oppressing marrow can increase probability of a miyelosupressiya.

Contraindications:

• hypersensitivity to a temozolomid or other components of drug, and also to a dakarbazin.
• the expressed miyelosupressiya.
• pregnancy.
• lactation period.
• children's age – up to 3 years (the recuring or progressing malignant glioma) or up to 18 years (for the first time the revealed multiformny glioblastoma or a malignant melanoma).
• Rare hereditary diseases, such as intolerance of a galactose, deficit of lactase or glyukozo-galaktozny malabsorption.

With care: advanced age (70 years are more senior) and the expressed renal or liver failure.

Overdose:

Symptoms: at use of drug in doses 500, 750, 1000 and 1250 mg/sq.m (the total dose received for a 5-day cycle of treatment) dozolimitiruyushchy toxicity was hematologic toxicity which was noted at reception of any dose, but is more expressed - at higher doses.

The overdose case (reception in a dose of 2000 mg/days within 5 days) is described as a result of which the pancytopenia, a pyrexia, multiorgan insufficiency and death developed. At administration of drug more than 5 days (up to 64 days), among other symptoms of overdose the hemopoiesis oppression complicated or not complicated by an infection, in certain cases long and expressed, with a fatal outcome was noted.

Treatment: the antidote to a temozolomid is not known. Hematologic control and if necessary - symptomatic therapy is recommended

Storage conditions:

To store drug in the unavailable to children, dry, protected from light place at a temperature from 2 °C to 25 °C. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

On 5 capsules in a strip packaging and a cardboard pack.