Index of drugs

Treatment of adult patients with newly-diagnosed glioblastoma multiforme in combination with radiotherapy and then monotherapy; children from 3 years, adolescents and adult patients with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy.

1 capsule contains 5 mg, 20 mg, 100 mg, 140 mg, 180 mg or 250 mg temozolomide; capsules contain lactose.

An anti-tumor drug with an alkylating activity, belonging to the triazene group. At physiological pH, it is rapidly converted to the active compound - MTIC, causing erroneous repair of methyl adducts. Temozolomide is rapidly absorbed from the gastrointestinal tract, reaching C_max within 20 minutes after administration. It is slightly bound to plasma proteins (10-20%). It quickly penetrates the blood-brain barrier and enters the cerebrospinal fluid. T_0,5 is 1.8 hours. It is mainly excreted by the kidneys.

Hypersensitivity to the active substance or any of the excipients. Hypersensitivity to dacarbazine. Severe myelosupression.

There is no clinical experience with the use of the drug in children under 3 years of age; in older children and adolescents these data are very limited. Use with caution in patients with impaired renal function. Due to the hepatotoxic effects of temozolomide, liver function tests should be performed before starting treatment. In the case of abnormal results, the decision to start treatment with temozolomide should be carefully considered, assessing the risks and benefits for the patient. Liver function tests should also be performed after each treatment cycle. In patients on a 42-day regimen, liver function tests should be repeated in the middle of the treatment cycle. In patients with significant hepatic impairment, the benefits and risks of continuing treatment should be carefully considered. Particularly cautiously use in the elderly, due to the increased risk of neutropenia and thrombocytopenia. All patients, especially those treated with steroids at the same time, should be monitored for the occurrence of pneumonia caused byPneumocystis carinii (pneumocystis carinii pneumonia - PCP). In all patients receiving temozolomide in combination with radiotherapy in a 42-day treatment regimen (up to a maximum of 49 days), regardless of the number of lymphocytes, it is necessary to use anti-PCP agents. If lymphopenia occurs, prophylaxis is applied until lymphopenia decreases to ≤ 1 degree. Antiemetic therapy can be implemented before or after administration of temozolomide. Patients with newly-diagnosed glioblastoma multiforme are advised to administer anti-emetic medication prior to the first dose of temozolomide; it is also advisable to administer antiemetics during monotherapy. Patients with malignant glioma showing recurrence or progression after standard therapy in whom severe vomiting (Grade 3 or 4) occurred during previous treatment cycles may require antiemetic treatment. Due to the lactose content, the drug should not be used in patients with rare congenital galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.

Do not use the preparation in pregnant women. If it is necessary to consider the use of the drug during pregnancy, the patient should be informed about the potential risk to the fetus (the risk of teratogenic and / or damaging the fetus). Women of childbearing age must use effective contraception and avoid getting pregnant while taking the product. Breast-feeding should be discontinued at the start of treatment with temozolomide. Due to the genotoxic effects of the drug, men treated with temozolomide should avoid conceiving a child during treatment and for not less than 6 months after the last dose of temozolomide.Treatment with temozolomide may cause irreversible infertility - the patient should be informed about the possibility of semen cryopreservation before starting treatment.

Newly diagnosed glioblastoma multiforme. In combination with radiotherapy. Very common: anorexia, headache, constipation, nausea, vomiting, rash, alopecia, fatigue. Common: infections, herpes simplex, wound infection, pharyngitis, oral candidiasis, neutropenia, thrombocytopenia, lymphopenia, leukopenia, hyperglycemia, weight loss, anxiety, emotional lability, insomnia, convulsions, decreased consciousness, drowsiness, aphasia, balance disorders, dizziness, confusion, memory problems, concentration disorders, neuropathy, parasthesia, speech disorders, tremors, blurred vision, hearing disorders, hemorrhage, edema, swelling of legs, shortness of breath, cough, stomatitis, diarrhea, abdominal pain, dyspepsia, dysphagia , dermatitis, dry skin, erythema, pruritus, muscle weakness, joint pain, increased urinary frequency, incontinence, allergic reactions, fever, radiation changes, facial edema, pain, dysgeusia, increased ALT. Uncommon: neutropenic fever, anemia, Cushing-like symptoms, hypokalemia, increased alkaline phosphatase, weight gain, agitation, apathy, behavioral disorders, depression, hallucinations, status epilepticus, extrapyramidal disorder, hemiparesis, ataxia, impaired cognitive ability, dysphasia, walking disorder, hypersensitivity to touch, reduced sensitivity to touch, neurological disorders (unspecified), peripheral neuropathy, hemiparesis, decreased visual acuity, visual disturbances, visual field defects, ocular pain, otitis media, tinnitus, hypersensitivity for sounds, earache, palpitations, cerebral hemorrhage, hypertension, pneumonia, upper respiratory tract infection, nasal congestion, exfoliation, photosensitivity reactions, pigmentation disorders, myopathy, back pain, osteo-muscular pain, muscle pain, impotence, asthenia, sudden redness, hot flushes, worsening of the general condition, chills, tongue discoloration, olfactory hallucinations, thirst, increase in AST, γ-GT.monotherapy. Very common: anorexia, convulsions, headache, constipation, nausea, vomiting, rash, alopecia, fatigue. Common: infections, oral candidiasis, neutropenic fever, thrombocytopenia, anemia, leukopenia, weight loss, anxiety, depression, emotional lability, insomnia, hemiparesis, aphasia, balance disorders, drowsiness, confusion, dizziness, impaired memory, impaired concentration , dysphasia, neurological disorders (undefined), neuropathy, peripheral neuropathy, paresthesias, speech disorders, tremors, visual field defects, blurred vision, double vision, hearing disorders, tinnitus, hemorrhage, deep vein thrombosis, leg edema, dyspnea, cough , stomatitis, diarrhea, dyspepsia, dysphagia, dry mouth, dry skin, pruritus, muscle weakness, joint pain, musculoskeletal pain, muscle pain, incontinence, allergic reactions, fever, radiation changes, pain, disorder taste, increase ALT activity. Uncommon: cold sores, shingles, flu-like symptoms, lymphopenia, ecchymosis, Cushing-like symptoms, hyperglycaemia, weight gain, hallucinations, amnesia, hemiplegia, ataxia, impaired coordination, walking disorder, sensitization, sensory disturbances, reduced focus sight, eye pain, dry eyeball, deafness, labyrinthine dizziness, earache, pulmonary embolism, edema, peripheral edema, pneumonia, sinusitis, upper respiratory tract infection, bronchitis, feeling of fullness in the abdomen, faecal incontinence , gastrointestinal disturbances (unspecified), gastritis, hemorrhoids, erythema, pigmentation disorders, exacerbation of sweating, myopathy, back pain, dysuria, vaginal bleeding, menorrhagia, amenorrhea, vaginitis, breast pain, asthenia, swelling of the face, pain, deterioration of the condition lnego, chills, dental disease, abnormal taste.Malignant glioma showing recurrence or progression. Very common: neutropenia or lymphopenia (grade 3-4), thrombocytopenia (grade 3-4), anorexia, headache, vomiting, nausea, constipation, tiredness. Common: weight loss, drowsiness, dizziness, paresthesia, shortness of breath, diarrhea, abdominal pain, dyspepsia, rash, pruritus, baldness, fever, weakness, muscle stiffness, malaise, pain, disorder of taste. Uncommon: pancytopenia, anemia (grade 3-4), leukopenia. Rarely: opportunistic infections, including pneumonia caused byPneumocystis carinii. Very rare: erythema multiforme, erythroderma, urticaria, exanthema, allergic reactions, including anaphylaxis, angioneurotic edema. In addition, the following side effects have very rarely been reported with post-marketing experience: cases of myelodysplastic syndrome and secondary tumors (including myeloid leukemia), toxic epidermal necrolysis, Stevens-Johnson syndrome, interstitial pneumonitis / pneumonitis, pulmonary fibrosis and failure fatal outcome (in particular in combination with Dexamethasone or other steroids). Long-term pancytopenia has been observed, which may lead to aplastic anemia, as well as cases of hepatotoxic effects, including increased liver enzymes, hyperbilirubinemia, cholestasis and hepatitis, including cases of fatal hepatic failure; toxic effects of temozolomide on the liver may occur a few weeks or more after the start of treatment or after discontinuation of temozolomide.

Orally.Adults with newly diagnosed glioblastoma multiforme: the drug is given in combination with radiotherapy (period of combination therapy), followed by up to 6 cycles as monotherapy.The period of combination therapy: 75 mg / m² pc. daily for 42 days in combination with targeted radiotherapy (60 Gy given in 30 doses). Combination therapy can be continued for 42 days (up to 49 days) if all of the following conditions are met: total neutrophil count ≥ 1.5 x 10⁹/ l, number of plates ≥100 x 10⁹/ l, non -hematologic toxicity according to CTC ≤1 degree (except for baldness, nausea and vomiting). During the treatment, blood tests should be performed once a week (morphology with a smear). Dose reduction is not recommended, but taking into account haematological and non-haematological toxicity, it may be delayed to administer the Next dose or stop administering temozolomide. Temozolomide should be temporarily interrupted during combination therapy if the total neutrophil count is ≥ 0.5 and <1.5 x 10⁹/ l or if the platelet count is ≥ 10 and <100 x 10⁹/ l or when there is non-haematological toxicity (except alopecia, nausea and vomiting) of the 2nd degree. Combination therapy with temozolomide can be continued if the parameters return to normal. Temozolomide should be completely discontinued during combination therapy if: total neutrophil counts <0.5 x 10⁹/ l or the number of plates <10 x 10⁹/ l or there is non-haematological toxicity (except alopecia, nausea and vomiting) of the 3rd or 4th degree.Monotherapy period: 4 weeks after the end of the combination treatment, monotherapy begins, using it for 6 cycles. In the first cycle of monotherapy, a dose of 150 mg / m is administered² pc. once a day for 5 days, followed by a 23-day break in drug administration. At the beginning of the 2nd cycle, the dose is increased to 200 mg / m² pc, if the non-hematologic toxicity during the first cycle was ≤ 2 degrees (except for baldness, nausea and vomiting), total neutrophil count ≥ 1.5 x 10⁹/ l and platelet count ≥100 x 10⁹/ L. If the dose is not increased in the second cycle, it should not be increased in subsequent cycles. Once increased to 200 mg / m² pc. daily dose is used on the first 5 consecutive days of each subsequent cycle, unless toxic effects occur. During the treatment, blood tests (morphology with a smear) should be performed on the 22nd day of the cycle (21 days after the first dose of temozolomide). You can adjust the dose by one level if toxicity occurs. Dosage levels include: 100 mg / m² pc. (level -1) - reduction due to previous toxicity; 150 mg / m² pc. (level 0) - dose during the first cycle; 200 mg / m² pc. (level 1) - dose in the period of 2.-6. cycle if there is no toxicity. The lowest recommended dose is 100 mg / m² pc.The dose should be reduced by one level if: the total neutrophil count is <1.0 x 10⁹/ l or number of plates <50 x 10⁹/ l or non-haematological toxicity (except alopecia, nausea and vomiting) grade 3 should occur. Drug discontinuation should be discontinued if dose level -1 (100 mg / m² p.) continues to cause high toxicity or if a non-haematological toxicity grade 4 occurs (except for baldness, nausea, vomiting) or if after the dose reduction the same third degree of toxicity occurs (except for baldness, nausea and vomiting).Adults and pediatric patients 3 years of age or older with malignant glioma showing recurrence or progression: the treatment cycle includes 28 days. Patients who have not received chemotherapy with temozolomide are given a dose of 200 mg / m² pc. once a day for the first 5 days, followed by a 23-day break in treatment (a total of 28 days). In patients undergoing previous chemotherapy, the initial dose is 150 mg / m² pc. once a day and can be increased in the second cycle to 200 mg / m² pc. once a day for 5 days, provided that there is no haematological toxicity.Special groups of patients. In patients with mild to moderate hepatic impairment, the pharmacokinetics of temozolomide are comparable to those with normal organ function. There are no data on the use of the drug in patients with severe hepatic impairment (Child-Pugh Class C) or with impaired renal function. Considering the pharmacokinetic properties of temozolomide, it is unlikely that a dose reduction would be required in patients with severe hepatic or renal impairment.
The drug should be administered on an empty stomach, with a glass of water. The capsules should be swallowed whole, they must not be opened or chewed. Anti-emetics may be given before or after administration. If vomiting occurs after taking the medicine, do not give your second dose on the same day.