Instruction for medical use of

TEMODEX

(information for healthcare professionals)

Trade name:

Temodex.

International non-proprietary name:

Temozolomide.

Description:

White to greenish-grey or brown powder.

Composition:

Active substance: temozolomide – 100 mg;

Excipient: dextran phosphate sodium salt – up to 1000 mg.

Presentation:

Powder for topical gel.

Pharmacotherapeutic group:

Antitumor alkylating agent.

ATC code:

L01AX03.

Pharmacological properties:

Pharmacodynamics

Temodex is an antitumor agent of prolonged action for topical use, which consists of temozolomide immobilized on a polymeric carrier – dextran phosphate sodium salt. Temozolomide is an imidazotetrazine agent with antitumor activity. When administered in the systemic circulation (in physiologic pH), it undergoes a rapid chemical transformation with the formation of an active compound – monomethyltriazenoimidazole carboxamide (MTIC). It is thought that the cytotoxicity of the latter is mainly due to alkylation of guanine at the O6 position and additional alkylation at the N7 position. The cytotoxic damage, which subsequently develops, is likely to trigger the mechanism of aberrant recovery of the methyl residue.

Pharmacokinetics

The pharmacokinetics of temozolomide immobilized on a polymeric carrier (dextran phosphate sodium salt) during the topical use of Temodex has not yet been studied. It is known that temozolomide is rapidly absorbed in the gastrointestinal tract following oral administration. The time to reach the peak concentration in blood (Сmax) is 0.5-1.5 h (the earliest time is 20 min). It penetrates the blood-brain barrier and gets into the cerebrospinal fluid. Half-life (T1/2) is 1.8 h. Plasma protein binding is 10-20%. Renal excretion: 5-10% in unchanged form and as 4-amino-5-imidazole-carboxamide hydrochloride or unidentified polar metabolites. The meal causes a decrease in Cmax by 33% and a reduction of the area under the pharmacokinetic curve (AUC) by 9%. In children, the AUC indicator is higher, but the maximum tolerated dose in children and in adults is the same (1 g/m2).

Therapeutic indications:

Intraoperative chemotherapy of malignant brain tumors, which are not subject to radical removal due to the characteristics of biological growth, with the view of local cytotoxic effect on residual tumor tissue, as well as prevention of recurrence and continued tumor growth. Therapeutic indications are: – newly diagnosed Glioblastoma multiforme (as a part of a combined treatment with X-ray therapy); – malignant glioma (glioblastoma multiforme or anaplastic astrocytoma).

Posology and route of administration:

The drug is administered intraoperatively. In the Temodex vial, 13-14 mL of water for injection is added and held for 20-30 min at an ambient temperature, regularly shaking up to swelling and gel formation. After removing as much of the brain tumor tissue as possible, an isolation of the porencephalic entry into the cerebral ventricle (if opened) is performed, careful hemostasis is ensured. After visualization of hemostasis, the prescribed gel mass is placed on the walls of the tumor bed, previously heated to a temperature of 37 °C.

Adverse effects:

The most common adverse effects are nausea, vomiting, increased fatigue, constipation, headache, decreased appetite, diarrhea, skin rash, fever, drowsiness, asthenia, abdominal pain, dizziness, weight loss, malaise, dyspnoea, dyspepsia, alopecia, chills, itching, taste perversion, paresthesia; marrow hematogenesis suppression (thrombocytopenia, neutropenia).

Contraindications:

Hypersensitivity (including to Dacarbazine), severe myelosuppression, pediatric use (by children up to 3 y.o. for the treatment of recurrent or progressive malignant glioma, and up to 18 y.o. for the treatment of newly diagnosed multiforme glioblastoma or malignant melanoma). Precautions for use patients with renal or hepatic impairment, elderly patients.

Pregnancy and breastfeeding:

Do not use during pregnancy and breastfeeding. The breastfeeding should be stopped during the treatment period.

Overdose:

With the local use of Temodex in recommended doses, overdose is unlikely.

Symptoms: neuro- and thrombocytopenia.

Treatment: there is no specific antidote, symptomatic therapy is carried out.

Interaction with other medicinal products:

Valproic acid inhibits the temozolomide clearance. Medicinal products that inhibit bone-marrow hematopoiesis and increase the risk of myelosuppression.

Special warnings and precautions:

Men and women should use effective contraception during the treatment and for 6 months after its completion. Requirements before use: absolute neutrophil count is not less than 1.5 thousand/μL, absolute PLT count is not less than 100 thousand/μL. For patients with severe vomiting (more than 5 episodes in 24 hours) – antiemetic therapy before and after treatment. During the treatment, hold back from driving and unsafe activities that require increased attention concentration and rapid psychomotor reactions. Cases of hepatic failure, including fatal hepatic impairment, have been reported in patients who have administered temozolomide orally. It is necessary to evaluate the indices of liver function before neurosurgical operation and intraoperative chemotherapy with Temodex. If laboratory parameters are abnormal, the benefit-risk ratio for intraoperative chemotherapy with Temodex, including the possibility of hepatic failure and death, should be carefully evaluated.

Storage conditions:

Keep in a dry place away from direct sunlight at a temperature below 25 °С. Keep out of reach of children.

Shelf life:

1.5 years. Do not use after the expiration date indicated on the package.

Prescription status:

Prescription only.

Packaging:

100 mg in glass vials No. 1 in cardboard packs with the Patient Information Leaflet.

Manufacturer:

UNITEHPROM BSU UE

1 Kurchatov Str., Minsk,

220045, Republic of Belarus

Tel./fax: +375 (17) 212-09-26 e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.