Tezalom^® (Capsules) Instructions for Use

ATC Code

L01AX03 (Temozolomide)

Active Substance

Temozolomide (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antineoplastic drug

Pharmacotherapeutic Group

Antineoplastic agent, alkylating compound

Pharmacological Action

An antineoplastic agent with alkylating action, it has an imidazotetrazine structure.

In the systemic circulation at physiological pH values, it undergoes rapid chemical conversion to form the active compound – monomethyltriazenoimidazolecarboxamide (MTIC). The cytotoxicity of MTIC is believed to be primarily due to the alkylation of guanine at the O⁶ position and additional alkylation at the N⁷ position. The cytotoxic damage resulting from this appears to trigger a mechanism of aberrant repair of the methyl residue.

Pharmacokinetics

After oral administration, it is rapidly absorbed from the gastrointestinal tract. The C_max of temozolomide in plasma is reached on average within 0.5-1.5 hours (minimum – after 20 minutes) after a single dose. When taken with food, a 33% decrease in C_max and a 9% decrease in AUC were observed.

Temozolomide rapidly crosses the blood-brain barrier and enters the cerebrospinal fluid. Plasma protein binding is 10-20%. The T_1/2 from plasma is approximately 1.8 hours. It is rapidly eliminated from the body mainly by the kidneys. Within 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.

Indications

Newly diagnosed glioblastoma multiforme (combined treatment with radiotherapy followed by adjuvant monotherapy); malignant glioma (glioblastoma multiforme or anaplastic astrocytoma) in case of relapse or disease progression after standard therapy; widespread metastatic melanoma (as a first-line therapeutic agent).

ICD codes

Dosage Regimen

Determine the dosage individually based on body surface area, clinical indication, and prior chemotherapy.

For newly diagnosed glioblastoma, administer two treatment phases: concomitant and adjuvant.

During the concomitant phase, administer 75 mg/m² once daily for 42 days concurrently with focal radiotherapy.

During the adjuvant phase, begin after a 4-week treatment break. Administer the drug for 5 days, followed by 23 days without treatment, constituting one 28-day cycle.

For the first adjuvant cycle, use a dose of 150 mg/m² once daily for 5 days.

For subsequent adjuvant cycles, increase the dose to 200 mg/m² once daily for 5 days if specific hematological criteria are met.

For refractory malignant glioma and metastatic melanoma, use an initial dose of 150 mg/m² once daily for 5 consecutive days per 28-day treatment cycle.

For subsequent cycles, increase the dose to 200 mg/m² once daily for 5 days if the nadir and day-of-dosing hematological parameters permit.

Adjust the dose or interrupt therapy based on the absolute neutrophil count and platelet count at the nadir and on the day of dosing.

For severe hematologic toxicity, reduce the dose or discontinue treatment as clinically indicated.

Administer capsules fasting, at least one hour before a meal, to ensure consistent absorption.

Do not open or chew the capsules; swallow them whole with a glass of water.

Handle the capsules with care to avoid exposure to the contents.

Adverse Reactions

Infections and infestations: oral candidiasis, Herpes simplex, Herpes zoster, pharyngitis, wound infection, reactivation of infections.

Benign, malignant and unspecified neoplasms: myelodysplastic syndrome, secondary malignant neoplasms, including myeloid leukemia.

Blood and lymphatic system disorders: leukopenia, lymphopenia, neutropenia, thrombocytopenia, anemia, febrile neutropenia, prolonged pancytopenia, aplastic anemia, petechiae.

Cardiac disorders: edema, hemorrhage, palpitations, increased blood pressure, cerebral hemorrhage, deep vein thrombosis, pulmonary embolism.

Respiratory, thoracic and mediastinal disorders: cough, dyspnea, bronchitis, pneumonia, upper respiratory tract infections, nasal congestion, interstitial pneumonitis, pulmonary fibrosis, respiratory failure.

Endocrine disorders: hypoglycemia, hyperglycemia, diabetes insipidus, Cushing’s syndrome.

Skin and subcutaneous tissue disorders: hyperhidrosis, alopecia, rash, dermatitis, dry skin, pruritus, facial edema, erythema, exanthema, photosensitivity reactions, pigmentation disorder, exfoliation, toxic epidermal necrolysis.

Nervous system disorders: headache, anxiety, emotional lability, insomnia, dizziness, balance disorder, impaired concentration, confusion and decreased consciousness, seizures, memory impairment, neuropathy, paresthesia, somnolence, speech disorders, tremor, agitation, apathy, behavioral disorders, depression, hallucinations, amnesia, perception disturbances, extrapyramidal disorders, dysphasia, ataxia, gait disturbance, hemiparesis, hyperesthesia, hypoesthesia, status epilepticus, peripheral neuropathies, parosmia, thirst.

Musculoskeletal and connective tissue disorders: arthralgia, muscle weakness, back pain, musculoskeletal pain, myalgia, myopathy.

Eye disorders: eye pain, hemianopia, visual disturbances, decreased visual acuity, visual field defects, diplopia.

Renal and urinary disorders: frequent urination, urinary incontinence, dysuria.

Reproductive system and breast disorders: impotence, vaginal bleeding, menorrhagia, amenorrhea, vaginitis, breast pain.

Ear and labyrinth disorders: hearing impairment, tinnitus, ear pain, hyperacusis, otitis media, deafness, vertigo.

Gastrointestinal disorders: anorexia, constipation, nausea, vomiting, abdominal distension, diarrhea, abdominal pain, dysphagia, stomatitis, taste disturbance, fecal incontinence, gastroenteritis, hemorrhoids, tongue discoloration.

Hepatobiliary disorders: increased ALT, AST, ALP activity, increased GGT activity, liver enzymes, hyperbilirubinemia, cholestasis, hepatitis, liver injury, hepatic failure.

Metabolism and nutrition disorders: hypokalemia, weight loss, weight gain.

General disorders and administration site conditions: increased fatigue, fever, flu-like syndrome, pain syndrome, allergic reactions (including anaphylaxis, angioedema), hot flashes, asthenia, general malaise, chills.

Contraindications

Hypersensitivity to temozolomide or to dacarbazine; severe myelosuppression; pregnancy, breastfeeding period; children under 3 years of age (recurrent or progressive malignant glioma) or under 18 years of age (newly diagnosed glioblastoma multiforme or malignant melanoma).

With caution elderly age (over 70 years); severe impairment of renal or liver function.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding). If use during lactation is necessary, the issue of discontinuing breastfeeding should be decided.

Use in Hepatic Impairment

Should be used with caution in patients with severe hepatic impairment.

Use in Renal Impairment

Should be used with caution in patients with severe renal impairment.

Pediatric Use

Contraindicated for use in children under 3 years of age (recurrent or progressive malignant glioma) or under 18 years of age (newly diagnosed glioblastoma multiforme or malignant melanoma).

Geriatric Use

Should be used with caution in elderly patients (since the risk of developing neutropenia and thrombocytopenia in persons over 70 years of age is higher than in younger individuals).

Special Precautions

Nausea and vomiting are often associated with the use of temozolomide, which is why prophylactic antiemetic therapy is recommended before starting combined treatment (with radiotherapy) and is strongly recommended during adjuvant therapy for newly diagnosed glioblastoma multiforme. Patients with recurrent or progressive glioma who experienced severe (grade 3 or 4) vomiting in previous treatment cycles may require antiemetic therapy.

Cases of hepatic failure, including fatal cases, have been reported during treatment with temozolomide. In this regard, liver function should be monitored before starting treatment. If indicators exceed the norm, the physician should assess the benefit/risk before starting therapy, including the risk of fatal hepatic failure. Liver function should be rechecked in the middle of the treatment cycle. Liver function should be monitored in all patients after each treatment cycle. In patients with significant deviations in liver function, the benefit/risk of continuing therapy should be assessed. Toxic liver damage can occur several weeks or more after the end of temozolomide use.

Men and women of childbearing potential during treatment with temozolomide and for at least 6 months after its completion should use reliable methods of contraception.

Due to the risk of irreversible infertility during treatment with temozolomide, male patients should be advised to discuss the possibility of sperm cryopreservation before starting treatment if necessary.

Effect on ability to drive vehicles and machinery

During the use of temozolomide, patients should exercise caution when driving vehicles and machinery, as well as when engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

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

With simultaneous use of temozolomide with other drugs that have a depressant effect on the bone marrow, an increased risk of myelosuppression is possible.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.