Active substanceTemozolomideTemozolomide
Similar drugsTo uncover
  • Astroglyph®
    capsules inwards 
    VEROPHARM SA     Russia
  • Thezalom®
    capsules inwards 
    KRKA-RUS, LLC     Russia
  • Temodal®
    capsules inwards 
  • Temodal®
    lyophilizate d / infusion 
  • Temodal®
    capsules inwards 
  • Temozolomide
    capsules inwards 
    BIOCAD, CJSC     Russia
  • Temozolomide
    capsules inwards 
    ARS, LLC     Russia
  • Temozolomide
    capsules inwards 
    ARS, LLC     Russia
  • Temozolomide
    capsules inwards 
    PSI-PHARMA, LLC     Russia
  • Temozolomide
    capsules inwards 
    NewVac, Inc.     Russia
  • Temozolomide-Rus
    capsules inwards 
    MANAS MED, LTD     Russia
  • Temozolomide-Teva
    capsules inwards 
  • Temozolomide-Teva
    capsules inwards 
  • Temozolomide-TL
    capsules inwards 
  • Temomide
    capsules inwards 
  • Temomide
    capsules inwards 
  • Temcital®
    capsules inwards 
    ANSTAR, AG     Switzerland
  • Dosage form: & nbspcapsules
    Composition:

    for 1 capsule 5 mg

    Active substance: temozolomide, substance-mixture 25.4 mg / g 197.00 mg [The active substance of the substance-mixture: temozolomide 5.00 mg

    Additives of substance-mixture: lactose 168.00 mg, silicon colloidal dioxide 1.00 mg, sodium carboxymethyl starch (type A) 16.00 mg, tartaric acid 7.00 mg]

    Excipients: stearic acid 3.00 mg

    Composition of hard gelatin capsule1 5 mg (No. 3):

    Housing: titanium dioxide (E171) 0.576 mg, gelatin q.s. up to 28.224 mg

    Cap: titanium dioxide (E171) 0.192 mg, gelatin q.s. up to 18,91968 mg, indigocarmine (E132) 0,0384 mg, dye quinoline yellow (E104) 0.04992 mg.

    1 capsule 20 mg

    Active substance: temozolomide, substance-mixture 507.6 mg / g 39.40 mg [The active substance of the substance-mixture: temozolomide 20.00 mg

    Additives of substance-mixture: lactose 14,60 mg, silicon dioxide colloid 0.20 mg, sodium carboxymethyl starch (type A) 3.20 mg, tartaric acid 1.40 mg]

    Excipients: stearic acid 0.60 mg

    Composition of hard gelatin capsule1 20 mg (No. 5):

    Housing: titanium dioxide (E171) 0.336 mg, gelatin q.s. up to 16.464 mg

    Cap: titanium dioxide (E171) 0.224 mg, gelatin q.s. up to 10.948 mg, the iron coloring agent is yellow (E172) 0.028 mg.

    for 1 capsule 100 mg

    Active substance: temozolomide, substance-mixture 507.6 mg / g 197.00 mg [The active substance of the substance-mixture: temozolomide 100.00 mg

    Additives of substance-mixture: lactose 73.00 mg, silicon dioxide colloid 1.00 mg, sodium carboxymethyl starch (type A) 16.00 mg, tartaric acid 7.00 mg]

    Excipients: stearic acid 3.00 mg

    Composition of hard gelatin capsule1 100 mg (No. 3):

    Housing: titanium dioxide (E171) 0.576 mg, gelatin q.s. up to 28.224 mg

    Cap: titanium dioxide (E171) 0.576 mg, gelatin q.s. up to 18,60672 mg, the iron dye red oxide (E172) 0.01778 mg. for 1 capsule 140 mg

    Active substance: temozolomide, substance-mixture 507.6 mg / g 275.80 mg [The active substance of the substance-mixture: temozolomide 140.00 mg

    Additives of substance-mixture: lactose 102.20 mg, silicon dioxide colloid 1.40 mg, sodium carboxymethyl starch (type A) 22.40 mg, tartaric acid 9.80 mg]

    Excipients: stearic acid 4.20 mg

    Composition of hard gelatin capsule1 140 mg (No. 1):

    Housing: titanium dioxide (E171) 0.912 mg, gelatin q.s. up to 44.688 mg

    Cap: titanium dioxide (E171) 0.304 mg, gelatin q.s. up to 30,05648 mg, indigocarmine (E132) 0,03952 mg. for 1 capsule 180 mg

    Active substance: temozolomide, substance-mixture 507.6 mg / g 354.60 mg [The active substance of the substance-mixture: temozolomide 180.00 mg

    Additives of substance-mixture: lactose 131.40 mg, silicon colloidal dioxide 1.80 mg, sodium carboxymethyl starch (type A) 28.80 mg, tartaric acid 12.60 mg]

    Excipients: stearic acid 5.40 mg

    Composition of hard gelatin capsule1 180 mg (No. 1):

    Housing: titanium dioxide (E171) 0.912 mg, gelatin q.s. up to 44.688 mg

    Cap: titanium dioxide (E171) 0.2432 mg, gelatin q.s. up to 29.58832 mg, ferric iron oxide yellow (E172) 0.2432 mg, ferric iron oxide red (E172) 0.32528 mg.

    for 1 capsule 250 mg

    Active substance: temozolomide, substance-mixture 507.6 mg / g 492.50 mg [The active substance of the substance-mixture: temozolomide 250.00 mg

    Additives of substance-mixture: lactose 182,50 mg, silicon dioxide colloid 2,50 mg, sodium carboxymethyl starch (type A) 40.00 mg, tartaric acid 17.50 mg]

    Excipients: stearic acid 7.50 mg

    Composition of hard gelatin capsule1 250 mg (No. 0):

    Housing: titanium dioxide (E171) 1.152 mg, gelatin q.s. to 56.448 mg Cap: titanium dioxide (E171) 0.768 mg, gelatin q.s. up to 37.632 mg.

    1 "Capsules", Belgium.

    Description:

    Capsules 5 mg:

    Hard gelatin capsules No. 3, capsule body white, lid green. Contents of capsules: powder from white / almost white to light pink / light brown color.

    Capsules 20 mg:

    Hard gelatin capsules No. 5, white capsule body, yellow lid. Contents of capsules: powder from white / almost white to light pink / light brown.

    Capsules 100 mg:

    Hard gelatin capsules No. 3, white capsule body, pink cap.Contents of capsules: powder from white / almost white to light pink / svekogo-brown color.

    Capsules 140 mg:

    Hard gelatin capsules number 1, the capsule body is white, the lid is transparent, blue. Contents of the capsules: powder from white / almost white to light pink / light brown.

    Capsules 180 mg:

    Hard gelatin capsules № 1, white capsule body, cap

    brownish red color. Contents of the capsules: powder from white / almost white to light pink / light brown.

    Capsules 250 mg:

    Hard gelatin capsules No. 0, capsule body and cap white. Contents of capsules: powder from white / almost white to light pink / light brown.

    Pharmacotherapeutic group:antitumor agent - alkylating compound
    ATX: & nbsp

    L.01.A.X.03   Temozolomide

    Pharmacodynamics:

    Tezalom® is an ego imidazotetrazine alkylating drug with antitumor activity. Upon entering the systemic circulation, at physiological pH values, it undergoes a rapid chemical transformation to form the active compound - monomethyltriazenoimidazolecarboxamide (MTIK).It is believed that the cytotoxicity of MTIC is due, first of all, to the alkylation of guanine in position O6 and additional alkylation in the N7. Apparently, cytotoxic lesions resulting from this include (trigger) the mechanism of aberrant reduction of the methyl residue.

    Pharmacokinetics:

    The preparation Tezalom® after intake is quickly absorbed and also quickly excreted from the body with urine. Preparation Thesalom® quickly penetrates the blood-brain barrier and enters the cerebrospinal fluid. The maximum concentration (Cmax) in plasma is achieved, on average, in 0,5-1,5 hours (the earliest - in 20 minutes) after taking the drug. The half-life of plasma is approximately 1.8 hours. The clearance, the volume of distribution in the plasma and the half-life do not depend on the dose. Preparation Thesalom ® weakly binds to proteins (12-16%). After oral administration of Tezal®, the average excretion rate with faeces for 7 days was 0.8%, indicating complete absorption of the drug. The main way of removing the drug Thesalom ® through the kidneys. 24 hours after ingestion, approximately 5-10% of the ingested dose is determined unchanged in the urine,the remainder is derived as 4-amino-5-imidazole-carboxamide hydrochloride (AIC), temozolomidic acid or unidentified polar metabolites. Taking the drug Thesalom ® together with food causes a decrease in Cmax by 33% and a decrease in the area under the "concentration-time" curve (AUC) on 9%.

    Clearance of the drug Thesalom ® in blood plasma does not depend on age, kidney function or tobacco consumption. Pharmacokinetic profile of the drug Thesalom ® in patients with impaired liver function of a mild to moderate degree, the same as in persons with normal liver function.

    In children, the indicator AUC higher than in adults. The maximum tolerable dose (MTD) in children and adults was the same and was 1000 mg / m2 for one treatment cycle.

    Indications:

    - The newly discovered multiform glioblastoma is a combined treatment with radiotherapy followed by adjuvant monotherapy;

    - malignant glioma (glioblastoma multiforme or anaplastic

    astrocytoma), in the presence of relapse or progression of the disease after standard therapy;

    - a common metastasizing malignant melanoma - as a first-line therapeutic agent.

    Contraindications:

    - Hypersensitivity to hemozolomide or other components of the drug, as well as to dacarbazine (DTIK);

    - severe myelosuppression;

    - pregnancy;

    - lactation period;

    - children under 3 years of age (recurrent or progressive malignant glioma) or up to 18 years of age (newly diagnosed glioblastoma multiforme or malignant melanoma);

    - rare hereditary diseases, such as galactose intolerance, lactase deficiency or pnukozo-galactose malabsorption.

    Carefully:

    - elderly age (over 70 beds);

    - marked renal and / or liver failure.

    Pregnancy and lactation:

    Preparation Thesalom ® contraindicated in pregnant women. Patients using the drug should be aware of the potential hazard to the fetus if the pregnancy occurs during treatment with the drug Thesal ® .

    It is not known whether Tezal® penetrates into breast milk, so it is necessary to stop either breastfeeding or therapy with Tezal®.

    Dosing and Administration:

    The preparation Tezalom ® is taken orally, on an empty stomach, at least one hour before meals.The prescribed dose should be taken using the lowest possible number of capsules. Capsules can not be opened or chewed, should be swallowed whole, washed down with a glass of water.

    The first identified multiforme glioblastoma Treatment of adult patients (over 18 years).

    Primary treatment conduct in combination with radiotherapy. Tezalom® is used at a dose of 75 mg / m2 daily for 42 days concurrently with radiotherapy (30 fractions in a total dose of 60 Gy) followed by 6 cycles of adjuvant therapy. Dose reduction is not recommended, but the drug may be interrupted depending on the tolerability. Renewal of the drug is possible during the entire 42-day period of combined treatment and up to 49 days, but only if all of the conditions listed below are met: the absolute number of neutrophils is not lower than 1500 / μL (1.5 × 109/ l), the number of platelets - not lower than 100000 / μl (100х109/ l), the toxicity criterion (CTC) is not higher than degree 1 (except for alopecia, nausea and vomiting). During treatment, a blood test should be performed weekly, counting the number of cells.Recommendations for dose reduction or withdrawal of Tezal® during the combined phase of treatment are given in Table 1.

    Table 1. Recommendations for a reduced dose or withdrawal of the drug Tezal® in combination treatment with radiotherapy

    Criterion of toxicity

    Break in taking the drug Tezalom® *

    Termination of the drug Tezalom®

    Absolute number of neutrophils

    > = 500 / μL (> 0.5 x 109/ l ), but <1500 / μL (<1.5x109/ l)

    <500 / μL (< 0.5x109/ l)

    Number of platelets

    > = 10000 / μL (> = 10 × 109/ l ), but

    <10000 / μL (< 10x 109/ l )


    <100000 / μL (< 100x 109/ l )

    CTC (non-hematologic toxicity, except for alopecia, nausea and vomiting)

    Degree 2

    Degree 3 or 4

    * Resumption of taking Tezal® is possible if all of the following conditions are met: absolute neutrophil count not lower than 1500 / μL (1.5 × 109/ l), the number of platelets is not lower than 100,000 / μL (100x 109/ l ), The toxicity criterion (CTC) is not higher than degree 1 (except for alopecia, nausea and vomiting). Adjuvant therapy is appointed 4 weeks after the completion of the combination therapy and is performed in the form of 6 additional cycles.

    Cycle 1: Tezalom® is administered at a dose of 150 mg / m2 for 5 days followed by a 23-day interruption in treatment.

    Cycle 2: The dose of Tezal® can be increased to 200 mg / m2 per day, provided that during the first treatment cycle, the severity of non-hematologic toxicity (in accordance with the STS toxicity scale) did not exceed the grade 2 (with the exception of alopecia, nausea and vomiting), while the absolute number of neutrophils was not lower than 1500 / μL (1,5x 109/ l ), and the number of platelets is not lower than 100,000 / μL (100x 109/ l ). If, in cycle 2, the dose of Tezal® has not been increased, sho should not be increased in the following cycles. If in cycle 2 the dose was 200 mg / m2, then in the same daily dose the drug is prescribed and in the following cycles (in the absence of toxicity). In each cycle, the preparation of Tezal® is administered for 5 consecutive days with a subsequent 23-day break.

    Recommendations for dose reduction in the adjuvant phase of treatment are given in Tables 2 and 3. On the 22nd day of treatment (21 days after taking the first dose of Tezal®), a blood test should be performed to count the number of cells. Abolition or reduction of the dose of Tezal® should be carried out according to Table 3.


    Table 2. The stages of dosing of the drug with Tezalum with adjuvant therapy

    Step

    Dose (mg / m2/ dey)

    Note

    - 1

    100

    Dose reduction taking into account the previous toxicity (see Table 3)

    0

    150

    Dose during cycle 1

    1

    200

    The dose during cycles 2-6 (in the absence of toxicity)


    Table 3. Recommendations for reducing the dose or drug withdrawal Thesal® with adjuvant therapy

    Toxicity Criteria

    Reduction of the dose of Tezal® preparation by 1 step (see Table 2)

    Termination of the drug Tezalom®

    Absolute number of neutrophils

    <1000 / μL (< 1.0x10%)

    sjc

    Number of platelets

    <50000 / μL (< 50x10%)

    *

    CTC (non-hematologic toxicity, except for alopecia, nausea and vomiting)

    Degree 3

    Degree 4 *

    * The drug Thesalom ® should be abolished if a dose reduction of <100 mg / m2, and also in case of recurrence of non-hematological toxicity degree 3 (except for alopecia, nausea and vomiting) after dose reduction.

    Progressive or recurrent malignant glioma in the form of a muliform glioblastoma or anaplastic astrocytoma (treatment of adults and children over 3 years old)

    A common metastasizing malignant melanoma (treatment of adults)

    In patients who had not previously received chemotherapy, Tezalom® was administered at a dose of 200 mg / m2 once a day for 5 consecutive days, followed by a break in taking the drug for 23 days (the total duration of one treatment cycle is 28 days).For patients who had previously undergone chemotherapy, the initial dose is 150 mg / m once a day, in the second cycle the dose can be increased to 200 mg / m2 per day for 5 days, provided that on the first day of the next cycle, the absolute amount neutrophils not lower than 1500 / μL (1,5x109/ l), and the number of platelets is not lower than 100,000 / μl (100x 109/ l ).

    Special patient groups

    Children

    Tezalom® in children 3 years of age and older should be used only with relapsing or progressive malignant glioma. The experience with temozolomide in children of this age group is very limited. Data on the use of temozolomide in children younger than 3 years are absent.

    Patients with hepatic or renal insufficiency

    The pharmacokinetic data of temozolomide in patients with normal liver function were comparable to those in patients with mild to moderate hepatic impairment. Data on the dosage regimen of Tezal ® in patients with severe hepatic insufficiency (class C according to the Child-Pyo scale) and renal failure are absent. Based on pharmacokinetics data, it is unlikely that a dose reduction in patients with severe hepatic insufficiency and any degree of renal failure is required.However, care should be taken when using the drug in these patient groups.

    Elderly patients

    Based on the data obtained by pharmacokinetic analysis in patients aged 19-78 years, the clearance of temozolomide does not depend on age. However, elderly patients (over 70 years of age) are at increased risk for developing neutropenia and thrombocytopenia.

    Recommendations for modifying the dose of Tezal in the treatment of progressive or recurrent malignant glioma or malignant melanoma

    In patients receiving the drug Tezal®, myelosunpression may develop, including prolonged pancytopenia. Perhaps the development of aplastic anemia, which in a few cases led to a fatal outcome. The development of aplastic anemia can also be associated with the use of a number of drugs, such as: carbamazepine, phenytoin or sulfamethoxazole / trimethoprim, therefore, with the simultaneous use of Tezal® and these drugs, it is difficult to establish the cause of the development of aplastic anemia.

    To begin treatment with Tezal ® is possible only with an absolute number of neutrophils> 1500 / μL (> 1.5 × 109/ l) and platelets> 100000 / μL (> 100x109/ l).A complete clinical blood test should be performed on day 22 (21 days after the first dose), but no later than 48 hours after this day and then on until the absolute number of neutrophils is above 1500 / μL (1,5x 109/ l ), and the number of platelets does not exceed 100,000 / μl (100x109/ l). With an absolute number

    neutrophils below 1000 / μL (1.0 × 109/ l) or platelets below 50,000 / μL (50x109/ l) during any treatment cycle, the dose in the next cycle should be reduced by one step. Possible doses: 100 mg / m, 150 mg / m and 200 mg / m2. The minimum recommended dose is 100 mg / m.

    Duration of treatment is maximum 2 years. If signs of disease progression appear, treatment with Tezal® should be discontinued.

    Side effects:

    The following undesirable phenomena noted when taking Tezal® are distributed according to the frequency of occurrence according to the following gradation: very often (> 10% of cases), often (> 1% to <10%), infrequently (> 0,1 % to <1%), rarely (from> 0.01% to <0.1%) and very rarely (<0.01%).

    The newly diagnosed multiform pili glioblastoma (adult patients) Combined phase of treatment (with radiotherapy)

    On the part of mechanisms of resistance to infections:

    often: candidiasis of the oral cavity, herpes simplex, pharyngitis, wound infection, other infection.

    From the side of the blood and lymphatic system:

    often: leukopenia, lymphopenia, neutropenia, thrombocytopenia;

    infrequently: anemia, febrile neutropenia.

    From the cardiovascular system: often: swelling, including legs, hemorrhage;

    infrequent: a feeling of heartbeat, increased blood pressure, cerebral hemorrhage.

    On the part of the respiratory system: often: cough, shortness of breath;

    infrequently: pneumonia, upper respiratory tract infection, nasal congestion.

    From the endocrine system: infrequently: the Itenko-Cushing syndrome.

    From the skin and subcutaneous fat, breast: very common: alopecia, rash;

    often: dermatitis, dry skin, erythema, skin itching, face swelling;

    infrequently: photosensitivity reactions, pigmentation disorders, exfoliation.

    From the nervous system: very often: headache;

    often: anxiety, emotional lability, insomnia, dizziness, aphasia, balance disorder, impaired concentration, confusion and decreased consciousness, convulsions, memory impairment, neuropathy, paresthesia, drowsiness, speech disorder, tremor;

    infrequently: agitation, apathy, behavioral disorders, depression, hallucinations, impaired perception, extrapyramidal disorders, dysphasia, ataxia, violation gait, hemiparesis, hyperesthesia, hypoesthesia, neurological disorders (unspecified), epileptic status, peripheral neuropathy, parosmia, thirst.

    From the musculoskeletal system: often: argalgia, muscle weakness;

    infrequently: back pain, musculoskeletal pain, myalgia, myopathy.

    From the side of the organ of vision: often: blurred vision;

    infrequently: pain in the eyes, gmiaanopsy, visual impairment, decreased visual acuity, limitation of visual fields.

    From the genitourinary system:

    Frequent: frequent urination, urinary incontinence;

    infrequently: impotence.

    From the organ of hearing and the vestibular system: often: hearing impairment;

    infrequently: pain in the ears, hyperacia, ringing in the ears, otitis media.

    From the digestive system. very often: anorexia, constipation, nausea, vomiting;

    often: increased activity of alanine aminotransferase, hyperglycemia, weight loss, abdominal pain, stomatitis, diarrhea, dyspepsia, dysphagia, impaired taste; infrequently: hypokalemia,increased alkaline phosphatase activity, weight gain, discoloration of the tongue, increased activity of gamma-glutamyltransferase, aspartate aminotransferase, liver enzymes.

    On the part of the body as a whole: very often: fatigue;

    often: fever, pain syndrome, radiation damage, allergic reaction; infrequently: "hot flashes" of heat to the body, asthenia, worsening of the condition, chills.

    Adjuvant phase of treatment

    On the part of mechanisms of resistance to infections:

    often: candidiasis of the oral mucosa, another infection;

    infrequently: herpes simplex, herpes zoster, influenza-like syndrome.

    From the side of the blood and lymphatic system:

    often: anemia, febrile neutropenia, leukopenia, thrombocytopenia; infrequently: lymphopenia, petechiae.

    From the cardiovascular system:

    often: swelling of the legs, hemorrhage, deep vein thrombosis;


    infrequently: edema, including peripheral, pulmonary embolism.

    On the part of the respiratory system: often: cough, shortness of breath;

    infrequently: pneumonia, infection of the upper respiratory tract, sinusitis, bronchitis.

    From the endocrine system: infrequently: the Itenko-Cushing syndrome.

    From the skin and subcutaneous fat, breast: very common: alopecia, rash; often: dry skin, itching of the skin;

    infrequently: erythema, a violation of pigmentation, increased sweating, pain in the breast, swelling of the face.

    From the nervous system: very often: headache, convulsions;

    often: anxiety, depression, emotional lability, insomnia,

    dizziness, aphasia, imbalance, impaired concentration, confusion, dysphasia, speech disorder, hemiparesis, memory impairment, neurological disorders (unspecified), neuropathy, peripheral neuropathy, paresthesia, tremor, drowsiness;

    infrequently: hallucinations, ataxia, impaired coordination, amnesia, gait disorders, hemiplegia, hyperesthesia, impaired sensory organs.

    From the side of the musculoskeletal system.

    often: arthralgia, musculoskeletal pain, myalgia, muscle weakness; infrequently: back pain, myopathy.

    From the side of the organ of vision:

    often: blurred vision, diplopia, limitation of visual fields; infrequently: pain in the eyes, dry eyes, reduced visual acuity.

    From the genitourinary system: often: urinary incontinence;

    infrequently: dysuria, amenorrhea, menorrhagia, vaginal bleeding, vaginitis.

    From the side of the hearing and vestibular system: often: hearing impairment, ringing in the ears; infrequently: deafness, pain in the ears, verge.

    From the digestive system: very often: anorexia, constipation, nausea, vomiting;

    often: increased activity of alanine aminotransferase, weight loss, diarrhea, dyspepsia, dysphagia, stomatitis, dryness of the oral mucosa, taste distortion;

    infrequently: hyperglycemia, weight gain, bloating, fecal incontinence, hemorrhoids, gastroenteritis, dental diseases, gastrointestinal-factor disorders.

    On the part of the body as a whole: very often: fatigue;

    often: fever, pain syndrome, radiation damage, allergic reaction; infrequently: asthenia, worsening of the condition, chills.

    Laboratory indicators

    Myelosuppression (neutropenia and thrombocytopenia) is a dose-limiting side effect. Among patients in both groups (combined and adjuvant therapy), neutrophil changes, including neutropenia, were noted in 8% of cases, and platelet counts, including thrombocytopenia, in 14% of cases.

    Progressive or recurrent malignant glioma (adults and children over 3 years old) or malignant melanoma (adults)

    On the part of the hematopoiesis system:

    very often: thrombocytopenia, neutropenia, lymphopenia;

    often: pancytopenia, leukopenia, anemia.

    In patients with glioma and metastatic melanoma, thrombocytopenia and grade 3 or 4 neutropenia were noted in 19% and 17%, respectively, in glioma and 20% and 22%, respectively, in melanoma. Hospitalization of the patient and / or removal of temozolomide, moreover, was required in 8% and 4% of cases, respectively, in glioma and in 3% and 1.3% in melanoma. The bone marrow depression developed usually during the first few treatment cycles with a maximum between 21 and 28 days, the recovery usually occurred within 1-2 weeks. No evidence of cumulative myelosuppression was noted.

    On the part of the digestive system:

    very often: nausea, vomiting, constipation, anorexia.

    often: diarrhea, abdominal pain, indigestion, taste perversion. The most frequent were nausea and vomiting. In most cases, these phenomena were 1-2 (from mild to moderate) degree of severity and passed independently or were easily controlled by standard anti-rheumatic therapy. Frequency of severe nausea and vomiting - 4%.

    From the nervous system: very often: headache;

    often: drowsiness, dizziness, paresthesia, asthenia, pain syndrome.

    From the skin and subcutaneous fat:

    often: rash, itching, alopecia, petechiae;

    very rarely: urticaria, exanthema, erythroderma.

    Other:

    very often: increased fatigue;

    often: weight loss, shortness of breath, fever, chills, general malaise;

    rarely: opportunistic infections, including pneumonia; very rarely: angioedema.

    Post-registration research data

    During postmarketing studies, very often there was a multiform erythema, toxic epidermal necrolysis, Stevens-Johnson syndrome, as well as allergic reactions, including anaphylaxis.

    There have been reports of hepatotoxicity, including increased activity of liver enzymes, hyperbilirubinemia, cholestasis and hepatitis. Very rarely there were violations of the liver, including cases with a fatal outcome.

    Opportunistic infections were rare, including pneumonia caused by Pneumocystis carnii, very rarely reported cases of interstitial pneumonitis and pneumonitis, as well as pulmonary fibrosis.Also, the development of myelodysplastic syndrome (MDS) and secondary malignant processes, including leukemia, was very rarely observed, and development of prolonged pancytopenia was very rare. Perhaps the development of aplastic anemia, which in a few cases led to a fatal outcome.

    Overdose:

    When using the drug in doses of 500, 750, 1000 and 1250 mg / m2 (the total dose received for a 5-day treatment cycle). Dose-limiting toxicity is hematologic toxicity, which was noted when taking any dose, but more pronounced - at higher doses. A case of overdose is described (taking a dose of 2000 mg per day for 5 days), which resulted in: pancytopenia, pyrexia, multiple organ failure and death. When taking the drug for more than 5 days (up to 64 days), among other symptoms of overdose, hematopoiesis was suppressed, complicated or uncomplicated by the infection, in some cases prolonged and severe, with a fatal outcome.

    Treatment

    The antidote to Tezal® is not known. It is recommended hematological control and, if necessary, symptomatic therapy.

    Interaction:

    The administration of temozolomide together with ranitidine does not lead to a clinically significant change in the degree of absorption of temozolomide.

    Joint reception with dexamethasone, prochlorperazine, phenytoin, carbamazepine, ondansetron, H2-histamine receptor antagonists or phenobarbital does not change the clearance of temozolomide. Joint administration with valproic acid results in a weak but statistically significant decrease in the clearance of temozolomide. Studies aimed at elucidating the effects of temozolomide on metabolism and excretion of other drugs have not been conducted. Due to temozolomide It is not metabolized in the liver and weakly bound by e proteins, its effect on the pharmacokinetics of other drugs is unlikely.

    The use of temozolomide together with other substances that depress the bone marrow may increase the likelihood of myelosuppression.

    Taking the drug Thesalom ® together with food causes a decrease in Cmax by 33% and decrease AUC on 9%.

    Special instructions:

    Prophylactic antiemetic therapy is recommended before the beginning of combined treatment (with radiotherapy) and is strongly recommended during adjuvant therapy for newly diagnosed multiform glioblastoma.If, against the background of treatment with Tezal®, nausea or vomiting occurs, it is recommended to perform antiemetic therapy in subsequent doses. Antiemetic drugs can be taken before and after taking Tezal®. Even if vomiting has developed in the first 2 hours after taking Tezal®, repeat the medication on the same day should not be.

    Due to the increased risk of developing pneumonia caused by Pneumocystis carinii, the patients receiving combined treatment with radiotherapy within 42 days (up to 49 days), such patients are recommended to carry out preventive treatment against the pathogen Pneumocystis carinii. Although the more frequent development of pneumonia caused by Pneumocystis carinii, is associated with longer duration of treatment with Tezal®, increased caution should be exercised with regard to the possible development of pivmocystis pneumonia in all patients receiving the drug Tezal *, especially in combination with glucocorticosteroids. The pharmacokinetic parameters of the preparation Tezalom® in persons with normal liver function and in patients with impaired liver function of mild or moderate severity are closely comparable.Data on the use of Tezal® in patients with severe hepatic impairment (class III according to the Child-Pyo classification) or renal dysfunction are present. Based on the data on the pharmacokinetic properties of the Tezal® drug, it seems unlikely that patients even with a marked impairment of liver or kidney function may need to reduce the dose of Tezal®. However, less so, when prescribing Tezal®, such patients should be cautious. Very rarely in the treatment with Tezal®, hepatic insufficiency, including fatal cases, was noted. In this regard, it is recommended to perform an analysis of liver function before starting treatment with Tezal®. During treatment, the patient should be under close medical supervision to assess the benefit / risk of continuing therapy.

    Men and women of childbearing age during treatment with Tezal® and, at least 6 months after the end, should use reliable methods of contraception.

    Because of the risk of developing irreversible infertility against the background of treatment with Tezal® To patients of a male before the beginning of treatment in case of need it is recommended to discuss an opportunity of cryopreservation of a semen.

    If the contents of the capsule (powder) get on the skin or mucous membranes, they must be rinsed with plenty of water.

    Effect on the ability to drive transp. cf. and fur:

    Some of the side effects of the drug on the part of the nervous system, such as drowsiness, fatigue, headache, dizziness and impaired concentration, can adversely affect the ability to drive vehicles or perform potentially dangerous activities requiring increased concentration and speed of psychomotor reactions.

    If the above undesirable phenomena occur, you should refrain from performing these activities.

    Form release / dosage:

    Capsules, 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, 250 mg.

    For 5 or 20 capsules in a bottle of dark glass with a volume of 15 ml, 30 ml or 50 ml, sealed with a screw-on plastic lid with the control of the first opening and protection from children. A label is attached to the vial. On 1 bottle together with the instruction but the application is placed in a pack of cardboard.

    Packaging:(20) - bottles of dark glass (1) - packs of cardboard
    (5) - bottles of dark glass (1) - packs of cardboard
    Storage conditions:

    At a temperature of no higher than 25 ° C, in the original packaging.

    Keep out of the reach of children.

    Shelf life:

    2 years.

    Do not use the drug after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-002850
    Date of registration:04.02.2015
    The owner of the registration certificate:KRKA-RUS, LLC KRKA-RUS, LLC Russia
    Manufacturer: & nbsp
    Information update date: & nbsp14.09.2015
    Illustrated instructions
      Instructions
      Up