Temodal, 140 mg capsules 5 pcs

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 C_max of temozolomide in plasma is reached on average 0.5-1.5 h (minimum 20 min) after a single dose. When taken with food, there was a 33% reduction in C_max and a 9% reduction in AUC.

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

The binding to plasma proteins is 10-20%.

The T_1/2 from plasma is approximately 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 remainder is excreted as 4-amino-5-imidazole-carboxamide hydrochloride or unidentified polar metabolites.

Indications

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

Pharmacological effect

Pharmacodynamics

Antitumor agent with alkylating action, has an imidazotetrazine structure.

In the systemic circulation at physiological pH values, it undergoes a rapid chemical transformation with the formation of the active compound – monomethyltriazenoimidazolecarboxamide (MTIC). It is believed that the cytotoxicity of MTIC is primarily due to alkylation of guanine at the O6 position and 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 quickly absorbed from the gastrointestinal tract.

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

Temozolomide quickly penetrates the BBB and enters the cerebrospinal fluid.

Plasma protein binding is 10-20%.

T1/2 from plasma is approximately 1.8 hours. It is quickly eliminated from the body mainly by the kidneys.

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

Special instructions

Use with caution in patients with severely impaired liver or kidney function, elderly patients (since people over 70 years of age have a higher risk of developing neutropenia and thrombocytopenia than younger people).

There is no clinical experience with glioblastoma multiforme in children under 3 years of age and 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 the ability to drive vehicles and other mechanisms that require increased concentration

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

Active ingredient

Temozolomide

Composition

1 capsule contains:

Active ingredients:

temozolomide 140 mg.

Excipients:

lactose,

sodium carboxymethyl starch,

colloidal silicon dioxide,

tartaric acid,

stearic acid.

Composition of the capsule shell:

titanium dioxide,

indigo carmine,

sodium lauryl sulfate,

gelatin.

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

There are 5 capsules in a dark glass bottle. There is 1 bottle in a cardboard package.

Pregnancy

Contraindicated during pregnancy and lactation (breastfeeding).

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

Contraindications

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

Side Effects

From the digestive system: nausea, vomiting, constipation, anorexia, diarrhea, abdominal pain, dyspepsia, taste disturbance.

From the central nervous system: fatigue, headache, drowsiness, dizziness, paresthesia.

Dermatological reactions: skin rashes, alopecia, itching.

From the respiratory system: shortness of breath.

From the hematopoietic system: thrombocytopenia and neutropenia of 3 or 4 degrees, pancytopenia, leukopenia and anemia.

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

Interaction

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

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

Overdose

When using the drug in doses of 500, 750, 1000 and 1250 mg/m2 (total dose received over a 5-day treatment cycle), the dose-limiting toxicity was hematological, which was observed at any dose, but more pronounced at higher doses.

A case of overdose (taking a dose of 2000 mg per day for 5 days) has been described, which resulted in pancytopenia, pyrexia, multiple organ failure and death.

When taking the drug for more than 5 days (up to 64 days), other side effects included suppression of hematopoiesis, complicated or uncomplicated by infection, in some cases long-term and severe, with a fatal outcome.

Treatment: There is no known antidote to Temodal. Hematological monitoring and, if necessary, symptomatic therapy are recommended.

Storage conditions

At 2–30 °C

Shelf life

2 years

Manufacturer

Orion Corporation Orion Pharma, Finland