Temodal, lyophilizate 100 mg

Pharmacodynamics

The alkylating antitumor agent has an imidazotetrazine structure.

In the systemic bloodstream at physiological pH values, it undergoes rapid chemical conversion to form the active compound, monomethyltriazenoimidazolcarboxamide (MTIC). It is believed that the cytotoxicity of MTIC is primarily due to the alkylation of guanine at the O6 position and an 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 oral administration, it is rapidly absorbed from the GI tract.

The Cmax of temozolomide in plasma is reached on average in 0.5-1.5 h (minimum 20 min) after a single dose. When taken with food, a 33% decrease in Cmax and a 9% decrease in AUC were observed.

Temozolomide penetrates rapidly through the BBB and enters the cerebrospinal fluid.

The binding to plasma proteins is 10-20%.

The T1/2 from plasma is about 1.8 h. It is rapidly excreted from the body mainly by the kidneys.

24 hours after oral administration about 5-10% of the dose is detected unchanged in the urine; the rest is excreted as 4-amino-5-imidazole-carboxamide hydrochloride or unidentified polar metabolites.

Indications

Active ingredient

Composition

1 vial contains:

Active substances:

Temozolomide 100 mg.

Associates:

mannitol 600 mg,

threonine 160 mg,

polysorbate 80 120 mg,

sodium citrate dihydrate 235.2 mg,

hydrochloric acid concentrated 160 mg.

In a bottle of colorless glass 100 mg of lyophilizate.

There is 1 vial in the carton pack.

How to take, the dosage

Individual, depending on age and prior chemotherapy.

Interaction

In concomitant use of temozolomide with valproic acid there is a weak, but statistically significant decrease in clearance of temozolomide.

The simultaneous use of temozolomide with other drugs that have a depressing effect on the bone marrow may increase the risk of myelosuppression.

Special Instructions

Cautiously use in patients with severe hepatic or renal dysfunction, elderly patients (because those over 70 years of age have a higher risk of neutropenia and thrombocytopenia than younger patients).

There is no clinical experience with glioblastoma multiforme in children under 3 years of age and with malignant melanoma in children and adolescents under 18 years of age. Clinical experience with glioma in children over 3 years of age is limited.

Impact on ability to drive vehicles and other mechanisms requiring increased concentration

Temozolomide may cause drowsiness and fatigue and therefore adversely affect the ability to drive and operate complex machinery.

Contraindications

Side effects

Digestive system disorders: nausea, vomiting, constipation, anorexia, diarrhea, abdominal pain, dyspepsia, taste disorders.

CNS disorders: fatigue, headache, drowsiness, dizziness, paresthesias.

Dermatological reactions: skin rashes, alopecia, itching.

Respiratory system: shortness of breath.

Hematopoietic system: thrombocytopenia and neutropenia of degree 3 or 4, pancytopenia, leukopenia and anemia.

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

Overdose

When the drug was used at doses of 500, 750, 1000, and 1250 mg/m2 (the total dose received over a 5-day treatment cycle), the dose-limiting toxicity was hematologic, which was noted at any dose, but more pronounced at higher doses. A case of overdose (taking a dose of 2000 mg daily for 5 days) resulting in pancytopenia, pyrexia, multiple organ failure and death has been described. When taking the drug longer than 5 days (up to 64 days), other side effects included suppression of hematopoiesis, complicated or uncomplicated by infection, in some cases prolonged and severe, with fatal outcome.

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