Active substanceTemozolomideTemozolomide
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  • Dosage form: & nbsplyophilizate for solution for infusion
    Composition:

    Active substance: temozolomide 100 mg.

    Excipients: manitol 600.0 mg, threonine 160.0 mg,

    nolisorbate-80 120.0 mg, sodium citrate dihydrate 235.2 mg, hydrochloric acid concentrated 160.0 mg.

    Description:Liofilizirovapny powder white with a pinkish tint of color, not containing mechanical inclusions.
    Pharmacotherapeutic group:antitumor agent, alkylating compound
    ATX: & nbsp

    L.01.A.X.03   Temozolomide

    Pharmacodynamics:

    Temozolomide is an imidazotetrazine alkylating drug with antitumor activity. If it enters the systemic circulation at physiological pH values, it undergoes a rapid chemical transformation to form the active compound - monomethyltriazosimidazolecarboxamide (MTIC). It is believed that the cytotoxicity of MTIC is due primarily to the alkylation of guanine in position O6 and additional alkylation in the N7. Apparently, the resulting cytotoxic lesions include (trigger) the mechanism of aberrant reduction of the methyl residue.

    Pharmacokinetics:

    Temozolomide quickly penetrates the blood-brain barrier and enters the cerebrospinal fluid. The half-life of plasma is approximately 1.8 hours. Clearance, the volume of distribution in the plasma and the half-life do not depend on the dose. Temozolomide weakly binds to proteins (12-16%).The main way to excrete tsmozolomida through the kidneys. After 24 hours, approximately 5% of the dose is determined unchanged in the urine; the remainder is in the form of 4-amino-5-imidazolecarboxamide hydrochloride (LIC), temozolomidic acid or unidentified polar metabolites.

    The clearance of the drug in plasma ns depends on age, kidney function or tobacco use. The pharmacokinetic profile of the drug in patients with impaired liver function of a mild to moderate degree is the same as in patients with normal liver function.

    In children, the indicator AUC (the area under the "concentration-time" curve) is higher than in adults. The maximum tolerated dose (MFA) in children and adults was the same and was 1000 mg / m2 for one treatment cycle.

    Indications:

    - the newly discovered multiform glioblastoma - combined treatment with radiotherapy followed by adjuvant monotherapy;

    - malignant glioma (glioblastoma multiforme or anaplastic astrocytoma) - if there is a relapse or progression of the disease after standard therapy;

    - a common metastatic malignant melanoma, as a first-line therapeutic.

    Contraindications:

    - hypersensitivity to temozolomide or other components of the drug, as well as to dacarbazip (DTIK);

    - marked myelosuppression;

    - pregnancy;

    - the period of breastfeeding;

    - children's age - up to 3 years (recurrent or progressive malignant glioma) or up to 18 years (newly diagnosed glioblastoma multiforme or malignant melanoma).

    Carefully:

    - older age (over 70 years);

    - a violation of the kidney or liver of severe severity.

    Pregnancy and lactation:

    The use of the drug Temodal® is contraindicated in pregnancy and during breastfeeding.

    Dosing and Administration:

    The newly discovered mules of non-glioblastoma

    Treatment of adult patients (over 18 years). Primary treatment conduct in combination with radiotherapy. The drug Temodal® is prescribed in a dose of 75 mg / m2 daily for 42 days at the same time as radiotherapy (30 fractions in a total dose of 60 Gy). Dose reduction ns is recommended, however, the drug intake may be interrupted depending on 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 the conditions listed below are met: the absolute number of neutrophils is not lower than 1500 / μL (1.5 × 10%), the number of platelets is not lower than 100,000 / μL (100 × 109/ l), the general toxicity criterion (CTC) is not higher than degree 1 (with the exception of alopecia, nausea and vomiting). During treatment, a blood test should be performed weekly, counting the number of cells. Recommendations for dose reduction or discontinuation of the preparation Temodal ® during the combined phase of treatment are given in Table 1.

    Table 1. Recommendations for dose reduction or withdrawal of the preparation Temodal ® when combined with radiotherapy

    Criterion of toxicity

    A break in taking the drug Temodal ® *

    Termination Temodal ®

    Absolute number of neutrophils

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

    <500 / μL (0.5 x 109/ l )

    Platelet count

    > = 10,000 / μL (10 × 109/ l ), but <100,000 / μL (100 × 109/ l )

    <10,000 / μL (10 × 109/ l )

    CTC non-hematological toxicity (with the exception of alopecia, nausea and vomiting)

    Degree 2

    Degree 3 or 4

    * Resumption of the drug Tsmodal ® possible if all of the following conditions are met: the absolute number of neutrophils is not lower than 1500 / μL (1.5 × 109/ l), the number of platelets is not lower than 100,000 / μl (100 × 109/ л), the general criterion of toxicity (СТС) - ns above degree I (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: the preparation Temodal® is prescribed in a dose of 150 mg / m2 for 5 days followed by a 23-day interruption in treatment. Cycle 2: the dose of Temodal® can be increased to 200 mg / m2 per day provided that in cycle 1 of treatment severity nsgematologicheskoy toxicity (according to the scale CTC toxicity) does not exceed 2 degrees (except for alopecia, nausea and vomiting), while the absolute number of neutrophils was not lower than 1500 / l (1.5 x 109/ l), and the number of platelets is not lower than 100,000 / μl (100 × 109/ l). If in cycle 2 the dose of the drug Temodal ® It has not been increased, it should not be increased in the next cycles. If in cycle 2 the dose was 200 mg / m2, in the same daily dose the drug is prescribed and in the following cycles (in the absence of toxicity). In each cycle, taking Temodal ® carry out for 5 consecutive days with a subsequent 23-day break. Recommendations to reduce the dose of adjuvant treatment phase are given in Tables 2 and 3. On day 22 of treatment (21 days after the first dose of the drug Temodal ® ) it is necessary to conduct a blood test with counting the number of cells. Cancellation or reduction of the dose of the drug Tsmodal ® should be carried out, guided by Table 3.

    Table 2. The dosage levels of the preparation Temodal ® with adjuvant therapy

    Step

    Dose (mg / m / day)

    Note

    - 1

    100

    Reduction of dose taking into account previous toxicity (see Table 3)

    0

    150

    Dose during cycle 1

    I

    200

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



    Table 3. Recommendations for dose reduction or discontinuation of the preparation Temodal ® with adjuvant therapy

    Criterion of toxicity

    Reduction of the dose of the drug Temodal ® by 1 step (see Table 2)

    Termination Temodal ®

    Absolute number of neutrophils

    <1000 / μL (1.0 x 109/ l)

    *

    Platelet count

    <50000 / μL (50 x 109/ l )

    *

    With TC non-hematologic toxicity (with the exception of alopecia, nausea and vomiting)

    Degree 3

    Degree 4 *

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

    Progressing or relapsing malignant glioma in the form of multiform glioblastoma or anaplastic astrocytoma (treatment of adults and children over 3 years old). Common metasogarnaya malignant melanoma (treatment of adults)

    Patients previously untreated with chemotherapy, the preparation Gsmodal is prescribed in 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 / m2 once a day; In the second cycle, the dose may be increased to 200 mg / m2 per day, provided that on the first day of the next cycle the absolute number of neutrophils is not lower than 1500 / μL (1.5 x 109/ l), and the number of platelets is not lower than 100,000 / μL (100 x 109/ l).

    Recommendations for modification of the dose of Temodal® in the treatment of progressive or recurrent malignant glioma or malignant melanoma

    In patients who use the drug Temodal ®, myelosuppression may develop, including prolonged pancytopenia. Possible development of aplastic anemia, which in isolated 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, fepitoin or sulfamethoxazole / trimethoprim, therefore, with the simultaneous use of Temodal and these drugs, it is difficult to establish the cause of the development of aplastic anemia.Initiate treatment with the drug Tsmodal ® is only possible with an absolute number of neutrophils> 1500 / μL (1,5 * 109/ l ) and platelets> 100,000 / μL (100 × 109/ l). A complete clinical blood test should be performed on day 22 (21 days after the first dose), but not later than 48 hours after that day; further - weekly, until the absolute number of neutrophils is above 1500 / μL (1.5 × 109/ l), and the number of platelets ns exceeds 100,000 / μl (100 × 109/ l). With an absolute number of neutrophils below 1000 / μL (1.0 × 109/ l) or platelets below 50,000 / μL (50 x 109/ l) during any treatment cycle, the dose in the next cycle should be reduced by one step (by 50 mg / m2).

    Duration of treatment is maximum 2 years. If signs of disease progression appear, treatment with Temodal® should be stopped. Preparation of a solution for infusions

    Preparation of the solution for infusion should be carried out in strictly aseptic conditions.

    41 ml of water for injections is added to the vial to dissolve the drug. Dissolution is carried out by rotating the vials, ns allowing shaking. The concentration of the resulting solution is 2.5 mg / ml of temozolomide. Vials with a solution containing visible mechanical inclusions can not be used.The reconstituted solution should be used within 14 hours, including the infusion time.

    Calculate the volume of solution required for administration. In aseptic conditions, up to 40 ml of solution is transferred from each vial to an empty 250 ml infusion bottle.

    The solution must be administered intravenously for 90 minutes.

    The solution is allowed to enter in one infusion system with a solution of sodium chloride 0.9%. The drug is incompatible with solutions of dextrose. Since compatibility studies of temozolomide. lyophilizate for the preparation of a solution for infusions, with other intravenous drugs or excipients have not been carried out, do not simultaneously inject them together using a single system.

    Side effects:

    The newly discovered multiformn glioblastoma (adult patients)

    The following are undesirable phenomena noted in the treatment of patients with newly diagnosed multiform glioblastoma during combined and adjuvant phases of treatment during clinical trials. The distribution and frequency of side effects was performed according to the following classification: very often (> 1/10), often (> 1/100 and <1/10), infrequently (> 1/1000 and <1/100).

    In the combined phase of treatment (with radiotherapy)

    Most of the adverse events are due to radiation therapy and are not associated with taking the drug.

    Infectious and parasitic diseases

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

    Violations from the blood and lymphatic system Often: leukopenia, lymphopenia, neutropenia, thrombocytopenia.

    Infrequently: anemia, febrile neutropenia.

    On the part of the endocrine system Infrequently: cushingoid.

    From the side of metabolism and nutrition Very often: anorexia.

    Often: hyperglycemia, weight loss.

    Infrequently: hypokalemia, increased alkaline phosphatase activity, weight gain.

    From the side of the psyche

    Often: anxiety, emotional lability, insomnia.

    Infrequently: agitation, apathy, behavioral disorders, depression, hallucinations.

    From the side of the nervous system Very often: headache.

    Often: convulsions, confusion, snotty, aphasia, imbalance, dizziness, confusion, memory impairment, impaired concentration, neuropathy, paresthesia, speech disorder, tremor.

    Infrequently: epileptic status, extrapyramidal disorders, hemiparesis, ataxia,impaired perception, dysphasia, gait disorders, hyperesthesia, gnepesthesia, neurological disorders (unspecified), peripheral neuropathy.

    From the side of the eye Often: blurred vision.

    Infrequently: hemianopia, decreased visual acuity, visual impairment, limitation of visual fields, pain in the eyes.

    From the side of the hearing organ and labyrinthine disorders Often: worsening of hearing.

    Infrequently: otitis media, ringing in the ears, hyperacusis, pain in the ears.

    From the heart

    Infrequently: a feeling of palpitations.

    From the side of the vessels

    Often: hemorrhage, swelling, incl. swelling of the feet.

    Infrequently: cerebral hemorrhage, increased blood pressure.

    From the respiratory system, chest and mediastinal organs Often: shortness of breath, cough.

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

    From the gastrointestinal tract Very often: constipation, nausea, vomiting.

    Often: stomatitis, diarrhea, abdominal pain, indigestion, dysphagia.

    From the skin and subcutaneous tissues Very often: rash, alopecia.

    Often: dermatitis, dry skin, erythema, skin itching.

    Infrequently: exfoliation, photosensitization reactions, pigmentation disorders.

    From the musculoskeletal and connective tissue Often: muscle weakness, arthralgia.

    Infrequently: Myopathy, back pain, musculoskeletal pain, myalgia.

    From the side of the kidneys and urinary tract Often: frequent urination, urinary incontinence.

    From the genital and breast (breast) infrequent infrequently: impotence.

    General disorders and disorders at the injection site Very often: increased fatigue.

    Often: allergic reaction, fever, radiation damage, edema of the face, pain syndrome, perversion of taste.

    Infrequently: asthenia, flushing, hot flushes, deterioration, chills, change in the language of color, distortion of the sense of smell, thirst.

    Laboratory and instrumental data

    Often: increased activity of alanine aminotransferase (ALT).

    Infrequently: increased activity of liver enzymes, gamma-glutamyltransferase, aspartate aminotransferase (ACT).

    In the adjuvant phase of treatment Infectious and parasitic diseases

    Often: Candidiasis of the oral mucosa, another infection.

    Infrequently: herpes simple, herpes zoster, green-like symptoms.

    Violations of the blood and lymphatic system

    Often: febrile neutropenia, thrombocytopenia, anemia, and leukopenia.

    Infrequently: lymphopenia, petechiae.

    From the endocrine system Not often: kunshigoid.

    From the side of metabolism and nutrition Very often: anorexia.

    Often: decrease in body weight.

    Infrequently: hyperglycemia, weight gain.

    From the side of the psyche

    Often: anxiety, depression, emotional lability, insomnia.

    Infrequently: hallucinations, amnesia.

    From the side of the nervous system Very often: convulsions, headache.

    Often: hemiparesis, aphasia, imbalance, drowsiness, depression, dizziness, memory impairment, concentration disorder, dysphasia, unsettled neurological disorders, neuropathy, peripheral neuropathy, paresthesia, speech disorder, tremor.

    Infrequently: hemiplegia, ataxia, decreased coordination, gait disturbance, hyperesthesia, sensory disturbances.

    From the side of the organ of vision

    Often: limitation of fields of vision, blurred vision, diplopia.

    Infrequently: decreased visual acuity, pain in the eyes, dry eyes.

    From the side of the hearing organ and labyrinthine disorders Often: hearing impairment, ringing in the ears.

    Infrequently: г a lohot, a vertex, a pain in ears.

    From the side of the vessels

    Often: hemorrhage, deep vein thrombosis, edema of the legs.

    Infrequently: pulmonary embolism, edema, peripheral edema.

    From the respiratory system, chest and mediastinum organs Often: shortness of breath, cough.

    Infrequently: pneumonia, sinusitis, upper respiratory tract infection, bronchitis.

    From the side .gastrointestinal tract Very often: constipation, nausea, vomiting.

    Often: stomatitis, diarrhea, dyspepsia, dysphagia, dryness of the oral mucosa. Infrequently: bloating, incontinence of the cap, gastrointestinal upset (unspecified), gastroenteritis, hemorrhoids.

    From the side of the rut and subcutaneous tissue Very often: rash, alopecia.

    Often: dry skin, itchy skin.

    Infrequently: erythema, impaired pigmentation, increased sweating.

    From the musculoskeletal and connective tissue

    Often: muscular weakness, arthralgia, musculoskeletal pain, myalgia.

    Infrequently: myopathy, back pain.

    From the nights and urinary tract Often: urinary incontinence.

    Infrequently: dysuria.

    From the genitals and (thoracic) gland

    Infrequently: vaginal bleeding, menorrhagia, amenorrhea, vaginitis, pain in the mammary glands.

    General disorders and disorders at the injection site Very often: increased fatigue.

    Often: allergic reaction, fever, radiation damage, pain syndrome, perversion of taste.

    Infrequently: asthenia, edema of the face, pain, deterioration, chills, dental disorders, perversion of taste.

    Laboratory and instrumental data

    Often: increased activity of alanine aminotransferase.

    Laboratory indicators

    Myelosuppression (neutropenia and thrombocytopenia) is a dozolimitating undesirable phenomenon. 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)

    The following undesirable phenomena noted when taking Temodal® are distributed according to the frequency of occurrence according to the following classification: very often (> 1/10), often (> 1/100 and <1/10), infrequently (> 1/1000 and <1/100), rarely (<1/1000), very rarely (<1/10000).

    Infectious and parasitic diseases

    Rarely: infections caused by conditionally pathogenic flora, including pneumocystis pneumonia.

    On the part of the hematopoiesis system

    Often: neutropenia or lymphopenia (3-4 degrees), thrombocytopenia (3-4 degrees).

    Infrequently: pancytopenia, anemia (3-4 degrees), and leukopenia. 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. Patient hospitalization and / or removal of Temodal® was required in 8% and 4% of cases, respectively, for glioma and 3% and 1.3% for melanoma. Oppression of the bone marrow developed usually during the first few cycles of treatment, with a maximum between 21 and 28 days; recovery occurred, usually within 1-2 weeks. No evidence of cumulative myelosuppression was noted. Thrombocytopenia can increase the risk of bleeding, and neutropenia or leukopenia can increase the risk of infection.

    From the side of metabolism and nutrition Very often: anorexia.

    Often: decrease in body weight.

    From the side of the nervous system Very often: headache.

    Often: drowsiness, dizziness, paresthesia.

    From the respiratory system, chest and mediastinal organs Often: dyspnea.

    On the part of the digestive system Very often: nausea, vomiting, constipation.

    Frequent: diarrhea, abdominal pain, indigestion. The most frequent were nausea and vomiting. In most cases, the phenomena were 1-2 (from mild to moderate) severity and passed independently or were easily controlled by standard antiemetic therapy. The frequency of severe nausea and vomiting is 4%.

    From the skin and subcutaneous fat Often: rash, itching. alopecia.

    Rarely: multiform erythema, erythroderma. hives, exanthema.

    General disorders and disorders at the injection site Very often: increased fatigue.

    Often: fever, asthenia, chills, malaise, pain, perversion of taste.

    Rarely: allergic reactions. including anaphylactic shock.

    angioedema.

    Temodal ® in the form of a lyophilizate for the preparation of a solution for infusion provides equivalent doses and the effect of both temozolomide. gak and its active metabolite MTIC (monomethyltriazanoimidazole carboxamide),similar to those with Temodal ® in the form of capsules. The following undesirable phenomena, probably associated with the use of the drug Temodal ® lyophilizate for solution for infusion, reported in two studies (n = 35) and are not represented in studies with the drug receiving Temodal ® form of capsules: in the place of infusion - pain, irritation, itching. sensation of heat, edema, erythema, as well as hematomas. Post-registration data

    In the post-registration period, very rarely reported cases of muliform erythema, toxic epidermal pecrolis. Stevens-Johnson syndrome and allergic reactions, including anaphylaxis. Also, reports of cases of geo-availability were received. including increased activity of liver enzymes, hyperbilirubinemia. cholestasis and hepatitis. Very rarely with Temodal ® hepatic insufficiency was noted, including fatal cases (see section "Special instructions"),

    In rare cases, opportunistic infections have been reported, including pneumonia caused by Pneumocystis carinii, and cases of reactivation of cytomegalovirus and hepatitis B. Very rarely reported cases of interstitial pneumonitis / nimeimmitis and pulmonary fibrosis. Also very rarely observed mnolodysilatic syndrome, metastatic malignant neoplasms, including myeloleukemia. There have been reports of prolonged pancytopenia, which could result in aplastic anemia, which in some cases led to death. There have also been cases of development of non-acharian diabetes.

    Overdose:

    Use of the drug in doses of 500. 750. 1000 and 1250 mg / m2 (total dose per cycle) was evaluated clinically in patients. Dose-limiting toxicity was hematologic toxicity, which was noted when taking any dose, but more expression, at higher doses. A case of overdose (taking a dose of 2000 mg per day for 5 days), which resulted in the development of paitsitopenia, piercing. polyhormal insufficiency 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 Temodal® is not known. It is recommended hematological control and, if necessary, symptomatic therapy.

    Interaction:

    Joint reception with dexamé lawn, prochlorperazion, fepitoinom. carbamazepine, optensetron, H2-receptor antagonists or phenobarbital does not alter 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 binds to proteins, its effect on the pharmacokinetics of other drugs is unlikely. Application of the preparation Temodal ® together with other substances that depress the bone marrow, may increase the likelihood of myelosuppression.

    Special instructions:

    Due to the increased risk of developing pneumonia caused by Pneumocystis carinii, in patients receiving combined treatment with radiotherapy for 42 days (up to 49 days), it is 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 periods of treatment with Temodal®, caution should be exercised with regard to the possible development of PCP in all patients receiving Temodal®, especially in combination with glucocorticosteroids.

    Antiemetic therapy

    Nausea and vomiting are often associated with taking Temodal ®, in connection with which it is recommended to carry out preventive antiemetic therapy before the beginning of combined treatment (with Lie therapy) and is highly recommended during adjuvant therapy of newly diagnosed multiform glioblastoma.

    Patients with recurrent or progressive glioma who have experienced severe (grade 3 or 4) vomiting in previous treatment cycles may need an anti-vomitingth therapy.

    Effect on kidney function

    The renal function, determined by the magnitude of creatinine clearance, did not affect the clearance of the drug Temodal ®

    Effect of neither liver function

    There is no evidence of the effect of Tsmodal® on liver function parameters, such as serum albumin, total protein,as well as liver function indicators such as alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (ACT) and bilirubin.

    Pharmacokinetic parameters of Temodal® in individuals with normal liver function and in patients with impaired liver function of mild or moderate severity (class I-II Child-Pyo) are comparable.

    Pharmacokinetic parameters in persons with severe impairment of liver function have not been adequately studied. These pharmacokinetics of tsmozolomide showed that a reduction in the dose of the drug in patients with mild and moderate hepatic insufficiency is not required.

    Very rarely, when treated with Temodal®, hepatic insufficiency, including fatal cases, was noted. In this regard, it is necessary to monitor liver function before starting treatment with Temodal®. If the indicators exceed the norm, the physician should assess the benefit / risk before the start of therapy, including the risk of developing a fatal liver failure. On the 42nd day of treatment (in the middle of the treatment cycle), it is necessary to repeatedly check the liver function. All patients need to monitor liver function after each treatment cycle.In patients with significant liver function abnormalities, the benefit / risk of continuing therapy should be evaluated. Toxic liver damage can occur several weeks or more after the end of the use of Temodal®.14

    Children

    There are no clinical data on the use of Temodal® in children under 3 years of age.

    Elderly patients

    In clinical studies in elderly patients (over 70 years) there was an increased risk of developing neutropenia and thrombocytopenia compared to younger patients.

    Men and women of childbearing age during the treatment with Temodal® and for at least 6 months after the termination should use reliable methods of contraception.

    Because of the risk of developing irreversible infertility during the treatment with Temodal® for male patients, it is recommended to discuss the possibility of cryopreservation of semen before the treatment if necessary.

    If the contents of the vial come into contact with the skin or mucous membranes, they should be rinsed with plenty of water.

    Effect on the ability to drive transp. cf. and fur:Some side effects of the drug, such as drowsiness and fatigue,can adversely affect the ability to drive vehicles or perform potentially dangerous activities that require increased concentration and speed of psychomotor reactions. Therefore, care should be taken when driving vehicles or performing potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions.
    Form release / dosage:Lyophilizate for the preparation of a solution for infusions of 100 mg.
    Packaging:

    Lyophilizate for the preparation of a solution for infusion, equivalent to 100 mg of active ingredient, into a bottle of colorless glass type I (Hebrew Pharm.) With a capacity of 100 ml, sealed with a rubber stopper and an aluminum crimping cap with a plastic snap-off cap.

    According to the I bottle, along with the instruction but application in a cardboard pack.
    Storage conditions:

    At a temperature of 2 to 8 ° C. Do not freeze.

    Keep out of the reach of children.

    Shelf life:4 years.
    Terms of leave from pharmacies:On prescription
    Registration number:PL-000847
    Date of registration:11.10.2011
    The owner of the registration certificate:Schering-Plau N. Labo.Schering-Plau N. Labo. Belgium
    Manufacturer: & nbsp
    Representation: & nbspMSD Pharmaceuticals Ltd.MSD Pharmaceuticals Ltd.
    Information update date: & nbsp15.09.2015
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