Temozolomide-TL - instructions for use, dose, side effects, contraindications

Active substance:	5 mg	For Dosage: 20 mg	100 mg
Temozolomide	5.00 mg	20.00 mg	100.00 mg
Excipients:
Lactose	49.18 mg	196.72 mg	61.72 mg
Silica colloidal dioxide	0.12 mg	0.48 mg	0.28 mg
Carboxymegil sodium starch	3.00 mg	12,00mg	9.00 mg
Wine acid	1.50 mg	6.00 mg	3.60 mg
Stearic acid	1.20 mg	4.80 mg	5.40 mg

Capsule shell:

Capsule hard gelatinous

[body: titanium dioxide - 2%, gelatin - up to 100%;
cap: titanium dioxide - 2%, dye yellow
sunset sunset (E110) - 0.219%, dye ..................................... No. 3 - 48.00mg
Azarubin (E122) 0.0328%, gelatin - up to 100%]

[body : titanium dioxide - 1%, iron dye
oxide yellow - 0.18%, gelatin - up to 100% ..................................... No. 2 - 61.00 mg
cap: titanium dioxide - 1%, iron dye
oxide yellow - 0.18%, gelatin - up to 100%

[body : titanium dioxide - 1%, iron dye
oxide yellow - 0.5%, gelatin - up to 100% ..................................... No. 1 - 76.00 mg
cap: titanium dioxide - 1%, iron dye
oxide yellow - 0.5%, gelatin - up to 100%

.................................................. .................................................................. ............... For dosage

Active substance.........................140 mg .............. 180 mg ................ 250 mg

Temozolomide .......................................140.00 mg .......... 180.00 mg .............. 250.00 mg

Excipients:

Lactose	86.41 mg	111.10 mg	154.30 mg
Silica colloidal dioxide	0.39 mg	0.50 mg	0.70 mg
Sodium carboxymethyl starch	12.60 mg	16.20 mg	22.50 mg
Wine acid	5.04 mg	6.48 mg	9.00 mg
Stearic acid	7.56 mg	9.72 mg	13.50 mg

Capsule shell:

Capsule hard gelatinous

[body: titanium dioxide - 1%, iron dye

oxide yellow - 0,192%, gelatin - up to 100%;

cover: iron dye oxide red - 0.93%, ................. No. 1 - 76.00 mg

dye iron black oxide - 0.53%, titanium

dioxide - 0.3333%, iron oxide dye

yellow - 0,2%, gelatin - up to 100%]

[body: titanium dioxide - 0.5265%, iron dye oxide yellow - 0.4343%, iron dye oxide black - 0.0224%, ferric oxide red oxide - 0.0224%, gelatin - up to 100%; lid: titanium dioxide - 0.6666%, iron oxide dye yellow 0.5%, iron dye oxide black 0.07%, iron oxide red oxide 0.07%, gelatin 100%..... .................................................. ........... No. 0 - 96.00 mg

[body: titanium dioxide - 2%, dye crimson [Ponso 4R] (E124) - 0.0153%, dye quinoline yellow - 0.0134%, gelatin - up to 100%; cover: titanium dioxide - 0.8%, dye azorubin (E122) - 0,6843 %, dye quinoline yellow - 0.1912%, dye crimson [Ponso 4R] (Е124) - 0,0336%, the dye diamond black (Е151) - 0,0192%, the dye is blue patented - 0,0088 %, gelatin - up to 100 %] ....... No. 0 - 96.00 mg

Description:

Capsules 5 mg - Hard gelatin capsules No. 3 with a white casing and an orange lid. The contents of the capsules are powder from white to pink or bark yellowish brown in color.

Capsules 20 mg - Hard gelatin capsules No. 2 with a body and a lid of yellow color. The contents of capsules - powder from white to pink or light yellowish-brownish color.

Capsules 100 mg - hard gelatin capsules No. 1 with a body and a lid of yellow color.Contents of capsules - powder from white to pink or light yellowish-brownish color.

Capsules 140 mg - Hard gelatin capsules No. 1 with a yellow body and a brown lid. The contents of capsules are powder from white to pink or light yellowish-brownish color.

Capsules 180 mg - hard gelatin capsules No. 0 with a yellow body with a brownish hue and a light brown lid. The contents of capsules - powder from white to pink or light yellowish-brownish color.

Capsules 250 mg - Hard gelatin capsules No. 0 with pink body and a burgundy lid. The contents of capsules - powder from white to pink or light yellowish-brownish color.

Pharmacotherapeutic group:antitumor agent, alkylating compound.

ATX: & nbsp

L.01.A.X.03 Temozolomide

Pharmacodynamics:

Temozolomide is an imidazotetrazine alkylating drug with antitumor activity. When entering the systemic circulation, at physiological values pH is subjected to a rapid chemical transformation to form the active compound - monomethyltriazenoimidazolecarboxamide (MTIK).It is believed that the cytotoxicity of MTIC is due primarily to the alkylation of guanine in position (Y 'and additional alkylation in position N⁷. Apparently, cytotoxic lesions resulting from this include (trigger) the mechanism of aberrant reduction of the methyl residue. The structure and synthesis of deoxyribonucleic acid, the cell cycle, is broken.

Pharmacokinetics:

Suction

After oral administration temozolomide quickly absorbed. The maximum concentration (Сmах) in plasma is reached on the average in 0,5-1,5 hours (the earliest - in 20 minutes) after reception of a preparation. Taking temozolomide together with food causes a decrease in C_max na 33% and a decrease in the area under the concentration-time curve (AUC) on 9%. Since it can not be ruled out that the change in C_max is clinically relevant, then apply temozolomide with impoverished ns recommended.

After oral administration of temozolomide, the average excretion rate with feces for 7 days was 0.8%, indicating complete absorption of the drug.

Distribution

Temozolomide quickly penetrates the blood-brain barrier and enters the cerebrospinal fluid.

The volume of distribution does not depend on the dose. Temozolomide weakly binds to blood proteins (12-16%).

Excretion

Quickly excreted from the body by the kidneys. Half-life period (TT / g) from the plasma is approximately 1.8 hours. The main way of removing temozolomide is the kidney. At 24 hours after ingestion, approximately 5-10% of the dose is determined unchanged in the urine; the remainder is recovered as 4-amino-5-imidazole-carboxa. hydrochloride, temozolomidic acid or unidentified polar metabolites. Clearance and T1 / 2 do not depend on the dose.

Pharmacokinetics in special clinical cases

The clearance of the drug in plasma does not depend on age, kidney function or smoking. 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 higher than in adults.

The maximum tolerated dose in children and adults was the same and was 1000 mg / m² for one treatment cycle.

Indications:

Temozolomide is indicated for treatment

- Adult patients with newly diagnosed multiform glioblastoma - combined treatment with radiotherapy (LT) followed by adjuvant monoterapy;

- children from the age of 3 years.adolescents and adult patients with malignant glioma, (glioblastoma multiforme or anaplastic astrocytoma), with relapse or disease progression after standard therapy;

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

Contraindications:

- hypersensitivity to temozolomide or other components of the drug, as well as to dacarbazine;

- a pronounced mission;

- pregnancy;

- the period of breastfeeding;

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

Carefully:

- should be appointed temozolomide patients older than 70 years;

- with severe renal or hepatic insufficiency;

- with rare hereditary diseases, such as lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Pregnancy and lactation:

Studies of the use of the drug temozolomide in pregnant women were conducted. Concerning, temozolomide contraindicated for use in pregnancy. Men and women of childbearing age during treatment with the drug temozolomida, and, at least 6 months after the end of treatment should use reliable methods of contraception.

There is no data on the penetration of temozolomide into breast milk. During the treatment with tsmozolomidom should abandon breastfeeding.

Because of the risk of irreversible infertility in the background of drug treatment temozolomide 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.

Dosing and Administration:

The drug Temozolomide-TL is taken orally, on an empty stomach, ns less than 1 h before meals. The prescribed dose should be taken using the lowest possible number of capsules. Capsules can not be opened or chewed, they should be swallowed whole, washed down with a glass of water.

The newly discovered multiform glioblastoma (treatment of adults over 18 years old).

Primary treatment is carried out in combination with radiotherapy. The drug Temozolomide-TL 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 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 following conditions are met: the absolute number of neutrophils is not lower than 1500 / μL. the number of platelets is not lower than 100,000 / μl, the general 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 elimination of hemosolomide during the combined phase of treatment are given in Table 1.

Table I. Recommendations for dose reduction or withdrawal of Temozolomide-TL in combination treatment with radiation therapy

Criterion of toxicity	Break in taking the drug Temozolomide-TL *	11 discontinuation of the drug Temozolomide-TL
Absolute number of neutrophils	> 500 / μL, but <1500 / μl	<500 / μL
Number of platelets	> 10000 / μl. but <100,000 / μL	<10000 / μL
ITS non-hematological
toxicity (with the exception of	Degree 2	Degree 3 or 4
alopecia, nausea and vomiting)
* Resumption of taking the drug	Temozolomide-TL is possible with	respect for all

the absolute number of neutrophils is not lower than 1500 / μl, the number of platelets is not lower than 100,000 / μl, the general 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: the drug Temozolomide-TL 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 Temozolomide-TL can be increased to 200 mg / m²/ day, provided that during the first cycle, the severity of non-hematologic toxicity (according to the STS toxicity scale) did not exceed degree 2 (with the exception of alopecia, nausea and vomiting), with the absolute number of neutrophils not lower than 1500 / μl, and the number of platelets - ns below 100,000 / μl. If the dose of Temozolomide-TL was not increased in cycle 2, it should not be increased in the following cycles. If, in cycle 2, the dose was 200 mg / m, in the same daily dose the drug is administered in the following cycles (in the absence of toxicity).In each cycle, the preparation Temozolomide-TL is administered for 5 consecutive days, followed by a 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 (the 21st day after taking the first dose of the drug), a blood test should be performed to count the number of cells. The cancellation or reduction of the dose of Temozolomide-TL should be carried out in accordance with Table 3.

Table 2. Dosage levels of Temozolomide-TL preparation with adjuvant therapy

Step	Dose l (mg / m / day)	Note
-1	100	Dose reduction taking into account previous toxicity (see Fig.
		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 a reduced dose or withdrawal of the drug Temozolomide-TL in adjuvant therapy

Criterion of toxicity	Reduce the dose of Temozolomide-TL preparation by 1 step (see Table 2)	Termination of the drug Temozolomide-TL
Absolute number of neutrophils	<1000 / μL	*
Platelet count	<50000 / μL	*
With GS non -hematological toxicity (with the exception of alopecia, nausea and vomiting)	Degree 3	Degree 4 *

* The drug Temozolomide-TL should be discarded,if a dose reduction of up to <100 mg / m is required and also in the case of recurrence of non-hematologic toxicity grade 3 (with the exception of alopecia, nausea and vomiting) after dose reduction.

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

A common metastasis of malignant melanoma (treatment of adults).

Patients who have not previously undergone chemotherapy, Temozolomide-TL preparation are 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 / m once a day; in the second cycle, the dose can be increased to 200 mg / m2 once a day for 5 days, provided that on the first day of the next cycle the absolute number of neutrophils is not lower than 1500 / μl, and the platelet count is not lower than 100,000 / μl.

Recommendations for modifying the dose of temozolomide in the treatment of progressive or recurrent malignant glioma or malignant melanoma Start treatment with Temozolomide-TL is possible only with an absolute number of neutrophils> 1500 / μL and platelets> 100,000 / μL. A complete clinical blood test should be performed on the 22nd day (the 21st day after taking the first dose), but no later than 48 hours after that day; then - weekly until the absolute number of neutrophils is above 1500 / μl, and the number of platelets ns exceeds 100,000 / μl. With an absolute neutrophil count below 1000 / μl or platelets below 50,000 / μL during any treatment cycle, the dose in the next cycle should be reduced by one step. Possible doses: 100 mg / m², 150 mg / m² and 200 mg / m². The minimum recommended dose is 100 mg / m².

Duration of treatment is maximum 2 years. When there is a progression of the disease, treatment with Temozolomide-TL should be stopped.

Side effects:

The newly discovered muliform glioblastoma (adult patients)

Table 4 below shows the side effects noted in the treatment of patients with newly diagnosed multiform glioblastoma during the combined and adjuvant phases of treatment during clinical trials (a causal relationship between drug intake and side effects of ns was established).

The distribution and frequency of side effects is in accordance with the following gradation: very often> 1/10. often from> 1/100 to <1/10, infrequently from> 1/1000 to <1/100:

Table 4. Side effects of the preparation Temozolomide-TL in the revealed multiform glioblastoma

Body systems	Frequency reactions	The nature of the reaction
Body systems	Frequency reactions	combined treatment phase (with radiotherapy) n = 288	adjuvant treatment phase n = 224
Mechanisms coupon 11 shali Yeni infections	often	Candidiasis of the oral mucosa, herpes simplex, pharyngitis, wound infection, other infection	Candidiasis of the oral mucosa, another infection
Mechanisms coupon 11 shali Yeni infections	infrequently		herpes simplex, herpes /.about stcr, influenza-like symptom
From the body as a whole	highly often	increased fatigue	increased fatigue

	often	fever, pain syndrome, radiation damage, allergic reaction	fever, pain syndrome, radiation damage, allergic reaction
	infrequently	"hot flushes" to the face, asthenia, worsening of the condition, chills	asthenia, worsening of the condition, chills
On the part of the hematopoiesis and lymphatic system	often	leukopenia, lymphopenia, neutropenia, thrombocytopenia	anemia, febrile neutropenia, leukopenia, thrombocytopenia
On the part of the hematopoiesis and lymphatic system	infrequently	anemia, febrile neutropenia	lymphopenia, petechia
From the side of the cardiovascular system	often	edema, including edema of the legs, hemorrhage	swelling of the legs, hemorrhage, deep vein thrombosis
From the side of the cardiovascular system	infrequently	heart beat, increased blood pressure, hemorrhagic stroke	edema, including peripheral edema, pulmonary embolism
From the side respiratory systems	often	cough, dyspnea	cough, dyspnea
From the side respiratory systems	infrequently	pneumonia, infection of the upper respiratory tract, nasal congestion	pneumonia, infection of the upper respiratory tract, sinusitis, bronchitis
From the endocrine system	infrequently	Isenko-Kushiig syndrome	Isenko-Cushing syndrome
From the nervous system	highly often	headache	headache, convulsions
From the nervous system	often	anxiety, emotional lability, insomnia, dizziness, balance disorder, concentration disorder, confusion and depression, aphasia, dysphasia, seizures, memory impairment, neuropathy, paresthesia, agitation drowsiness, speech disorder, tremor,	anxiety, depression, emotional lability, insomnia, dizziness, balance disorder, impairment concentration, ataxia, confusion, aphasia, dysphasia, speech disorder, hemiparesis, memory impairment, neurological disorders (not tired), neuropathy,

			peripheral herpes, paresthesia, drowsiness, tremor
	infrequently	apathy, behavioral disorders, depression, hallucinations, impaired perception, extrapyramidal disorders, ataxia, impaired coordination, hemiparesis, hyperesthesia, hypoesthesia, neurological disorders (unspecified), peripheral neuropathy, epileptic statue, narosmia, thirst	hallucinations, amnesia, ataxia, impaired coordination, hemiplegia, hyperesthesia, sensitivity disorder / sensory disorders
From the skin and subcutaneous tissue, milk of the glands	highly often	alopecia, rash	alopecia, rash
	often	dermatitis, dry skin, erythema, itchy skin, face swelling	dry skin, itchy skin
	infrequently	photosensitivity, pigmentation disorder, exfoliation	erythema, pigmentation disorder, facial edema, increased sweating, pain in the mammary gland
From the side musculoskeletal systems	often	arthralgia, muscle weakness	arthralgia, muscle weakness, myalgia. musculoskeletal pain
From the side musculoskeletal systems	infrequently	back pain, musculoskeletal pain, myalgia, myopathy	back pain, myopathy
From the side of the organ of vision	often	blurred vision	blurred vision, diplopia, visual field limitation
From the side of the organ of vision	infrequently	pain in the eye, hemianosis. impaired vision, reduced visual acuity, limited vision	pain in the eye, dry eyes, decreased visual acuity
On the part of the organs of hearing and vestibular systems	often	hearing impairment	hearing impairment, ringing in the ears
	infrequently	Ear pain, hyperacia, otitis media, ringing in the ears	deafness, earache, dizziness
From the side digestive systems	highly often	anorexia, constipation, nausea, vomiting	anorexia, constipation, nausea, vomiting
From the side digestive systems	often	increased activity of alanine aminotraneferase,	increase in activity of alaninam inotransfera-

		hyperglycemia, weight loss, abdominal pain, diarrhea, dyspepsia, dysphagia. stomatitis, taste disorder	weight loss, diarrhea, dyspepsia, dysphagia, stomatitis, dry mouth. taste disorder
	infrequently	hypokalemia, increased alkaline phosphatase activity, weight gain,change in the color of the tongue, increased activity of gamma-glutamyltranspeptidase, aspartate aminotransfsrase, liver enzymes	hyperglycemia, weight gain, bloating, fecal incontinence, hemorrhoids, gastroenteritis, dental diseases
FROMabout the part of the genitourinary system	often	frequent urination, urinary incontinence	urinary incontinence
FROMabout the part of the genitourinary system	infrequently	impotence	dysuria, amenorrhea, msnorrhagia, vaginal bleeding, vagiMr.um

Laboratory indicators: misoperation (neutropenia and thrombocytopnia),

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)

The undesirable events listed below when taking Temozolomide-TL are distributed according to the frequency of occurrence according to the following gradation: very often> 1/10, often> 1/100 to <1/10. infrequently from> 1/1000 to <1/100.rarely from> 1/10000 to <1/1000 and very rarely <1/10000.

On the part of the hematopoiesis system: often - thrombocytopenia, neutropenia, lymphopenia; infrequently - pancytopenia, leukopenia, anemia. In the treatment of patients with glioma and metastatic melanoma, thrombocytopenia and netsotropes of grade 3 or 4 were noted in 19% and 17%, respectively, in glioma and 20% and 22%, respectively, in melanoma. Hospitalization of the patient and / or withdrawal of the drug Temozolomide-TL it was required in 8% and 4% of cases, respectively, in glioma and in 3% and 1.3% in 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.

From the digestive system: very often - nausea, vomiting, anorexia, constipation; often - diarrhea, abdominal pain, indigestion, perversion of taste. The most frequent were nausea and vomiting. In most cases, these phenomena were 1-2 (from mild to moderate) severity and passed independently or were easily controlled by standard anti-rupture therapy.The frequency of severe nausea and vomiting is 4%.

From the nervous system: often - headache; often - drowsiness, dizziness, paresthesia, asthenia.

From the skin and subcutaneous tissue: often - rash, itching, alopecia, pstschia; very rarely - urticaria, exanthema, erythroderma, erythema multiforme, toxic epidermal nscrolisis, Stevens-Johnson syndrome.

From the immune system: very rarely - allergic reactions, including anaphylaxis.

Other: often - increased fatigue; often - weight loss, shortness of breath, fever, chills, general malaise; rarely opportunistic infections, including pneumonia caused by Pneumocystis carinii; very rarely observed the development of mildodysplastic syndrome and secondary malignant processes, including leukemia, as well as the development of prolonged pancytopenia with a risk of developing aplastic anemia and irreversible infertility.

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, report about this doctor.

Overdose:

When using the drug at doses of 500 mg / m, 750 mg / m, 1000 mg / m and 1250 mg / m2 (total dose,received for a 5-day treatment cycle), hematologic toxicity was observed with dose-limiting toxicity, which was noted at any dose, but more pronounced - at higher doses. The case of overdose (taking a dose of 2 g / day for 5 days), which resulted in the development of 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 complicated, complicated or complicated by infection, in some cases prolonged and severe, with a fatal outcome.

Treatment: the antidote is unknown. It is recommended hematological control and, if necessary, symptomatic therapy.

Interaction:

The administration of temozolomide together with ranitidine nc leads to a clinically significant change in the degree of absorption of temozolamide.

Joint reception with dexamstasone, prochlorperazine, phenytoin, carbamazepine, ondansetron, histamine H2 receptor blockers or phenobarbital does not change the clearance of temozolamide.

Joint administration with valproic acid causes a weak but statistically significant decrease in the clearance of temozolamide.

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.

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

Special instructions:

Prophylactic and anti-retroviral 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 Temozolomide-TL, nausea or vomiting occurs in subsequent doses, it is recommended that an anti-emetic therapy be performed. Antiemetic drugs can be taken both before and after taking the drug Temozolomide-TL. Even if vomiting has developed in the first 2 hours after taking the drug Temozolomide-TL repeat the reception of the drug on the same day should not be.

Due to the increased risk of developing pneumonia caused by Pneumocystis carinii, in 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 Temozolomide-TL, increased alertness to the possible development of mnosocial pneumonia should be shown for all patients receiving temozolomide, especially in combination with glucocorticosteroids.

Special patient groups

Children 3 years of age and older temozolomide is prescribed with relapsing or progressing malignant glioma. There is limited experience with the use of temozolomide in glioma in children older than 3 years. Clinical experience of the use of the drug Tsmozolomide-TL with multiform glioblastoma in children under 3 years old and with malignant melanoma in children and adolescents under the age of 18 is absent. The safety and efficacy of temozolomide in children younger than 3 years has not been established. Patients with hepatic or renal insufficiency. The pharmacokinetic parameters of temozolomide in patients with normal liver function and in patients with impaired liver function of mild or moderate severity are closely comparable. Data on the use of temozolomide in patients with severe impairment of liver function (class C on the Child-Pyo scale) or impaired renal function are present. Based on the data on the study of the pharmacokinetic properties of temozolomide, it seems unlikely that patients even with a marked impairment of liver or kidney function may need to reduce the dose of the drug. However, when prescribing the drug Tsmozolomid-TL such patients should be cautious.

Patients of advanced age. The pharmacokinetics of temozolomide does not depend on age. However, in elderly patients older than 70 years, the risk of developing neutropenia and thrombocytopenia is higher than in younger patients. Therefore, elderly patients with tsmozolomid should be administered with caution.

If the contents of the capsule (powder) get on the skin or mucous membranes, rinse them 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.

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 and 250 mg.

For 5 or 20 capsules in a jar (bottle) for medicines made of plastic with a lid with a desiccant.

Free space in the jar (bottle) is filled with cotton absorbent medical cotton.

Each jar (bottle), together with the instruction for use, is placed in a pack of cardboard box.

Packaging:(20) - plastic cans (1) - packs of cardboard
(20) - plastic bottles (1) - packs cardboard
(5) - plastic cans (1) - packs of cardboard
(5) - plastic bottles (1) - packs cardboard

Storage conditions:

In the dark place at a temperature of ns above 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002995

Date of registration:15.05.2015

The owner of the registration certificate:TECHNOLOGY OF DRUGS, LTD. TECHNOLOGY OF DRUGS, LTD. Russia

Manufacturer: & nbsp

TECHNOLOGY OF DRUGS, LTD. Russia

Information update date: & nbsp14.09.2015

Illustrated instructions

Instructions

Temozolomide-TL (Temozolomide-TL)