Drug capsules 180mg №5

Composition

1 capsule contains:

Active substances: temozolomide 180 mg.

Excipients: lactose, sodium carboxymethyl starch, colloidal silicon dioxide, tartaric acid, stearic acid.

The composition of the shell of the capsule: titanium dioxide, indigo carmine, sodium lauryl sulfate, gelatin.

The composition of the ink for printing on the capsule shell: black dye (shellac, ethanol, isopropanol, butanol, propylene glycol, purified water, ammonia water, potassium hydroxide, iron dye black oxide).

pharmachologic effect

Pharmacodynamics

The antitumor agent of the alkylating action has an imidazotetrazinovuyu structure.

In the systemic circulation, under physiological pH, it undergoes a rapid chemical transformation with the formation of the active compound, monomethyltriazenoimidazolecarboxamide (MTIK). It is believed that the cytotoxicity of MTIK is due primarily to the alkylation of guanine at the O6 position and the additional alkylation at the N7 position. Apparently, the cytotoxic damage resulting from this triggers the mechanism of aberrant reduction of the methyl residue.

Pharmacokinetics

After ingestion is rapidly absorbed from the gastrointestinal tract.

C_max plasma temozolomide is achieved on average in 0.5-1.5 hours (minimum - in 20 minutes) after taking a single dose. When taken with food, a decrease in C was observed._max by 33% and a decrease in AUC by 9%.

Temozolomid quickly penetrates the BBB and enters the cerebrospinal fluid.

Plasma protein binding is 10-20%.

T_1/2 from plasma is approximately 1.8 hours. Quickly excreted mainly by the kidneys.

24 hours after ingestion, about 5-10% of the dose is determined unchanged in the urine; the remainder is displayed as 4-amino-5-imidazole-carboxamide hydrochloride or unidentified polar metabolites.

Indications

• Malignant gliomas (including glioblastoma multiforme, anaplastic astrocytoma) in the presence of recurrence or progression of the disease after standard therapy;
• common metastatic malignant melanoma (as a first-line therapeutic agent).

Contraindications

• Severe myelopepression;
• pregnancy;
• lactation (breastfeeding);
• hypersensitivity to temozolomide or dacarbazine.

Use during pregnancy and lactation

Contraindicated in pregnancy and lactation (breastfeeding).

Men and women of childbearing age should use effective contraceptives during treatment and for at least 6 months after the end of treatment.

special instructions

Use with caution in patients with severely impaired liver or kidney function in elderly patients (as in those over 70, the risk of developing neutropenia and thrombocytopenia is higher than in younger patients).

Clinical experience with glioblastoma multiforme in children under 3 years of age and with malignant melanoma in children and adolescents under 18 is absent. Clinical experience with glioma in children older than 3 years is limited.

Influence on the ability to drive vehicles and other mechanisms that require high concentration of attention

Temozolomid can cause drowsiness and fatigue and therefore adversely affect the ability to drive vehicles and manage complex mechanisms.

Dosage and administration

Individual, depending on age and previous Chemotherapy.

Side effects

Gastrointestinal: nausea, vomiting, constipation, anorexia, diarrhea, abdominal pain, dyspepsia, taste disturbance.

From the side of the central nervous system: fatigue, headache, drowsiness, dizziness, paresthesias.

Dermatologic: skin rashes, alopecia, pruritus.

Respiratory: dyspnea.

Hemic and lymphatic: thrombocytopenia and grade 3 or 4 neutropenia, pancytopenia, leukopenia and anemia.

Other: fever, asthenia, weight loss, malaise, chills.

Drug interaction

With simultaneous use of temozolomide with valproic acid, a mild, but statistically significant decrease in temozolomide clearance is observed.

About the simultaneous use of temozolomide with other drugs that have a depressant effect on the bone marrow, you may increase the risk of developing myelosuppression.

Overdosage

When using the drug in doses of 500, 750, 1000 and 1250 mg / m² (the total dose received for the 5-day cycle of treatment) was hematologic dose-limiting toxicity, which was observed when taking any dose, but more pronounced with higher doses. A case of overdose has been described (receiving a dose of 2000 mg per day for 5 days), as a result of which pancytopenia, pyrexia, multiple organ dysfunction and death have developed.When taking the drug for more than 5 days (up to 64 days), among other side effects, hematopoiesis oppression was noted, complicated or not complicated by infection, in some cases - prolonged and severe, with fatal outcome.

Treatment: antidote to Temodal unknown. Hematological control and, if necessary, symptomatic therapy are recommended.

Storage conditions

Store at 2-30 ° C.