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

Excipients: lactose 182.2 mg sodium carboxymethyl starch 11.0 mg 4.4 mg stearic acid, tartaric acid 2.2 mg colloidal silica 0.2 mg hard gelatin capsule [titanium dioxide (E171), gelatin, iron oxide colorant yellow (E172), indigocarmine (E132)].

Dosage 100 mg

Active substance: temozolomide 100 mg.

Excipients: lactose 175.7 mg, sodium carboxymethyl starch 15.0 mg, stearic acid 6.0 mg, tartaric acid 3.0 mg, silicon dioxide colloidal 0.3 mg, hard gelatin capsule [titanium dioxide (E171), gelatin, dye crimson [ Ponceau 4R] (E124), the iron dye red oxide (E172)].

Dosage 140 mg

Active substance: temozolomide 140 mg.

Excipients: lactose 246.0 mg, sodium carboxymethyl starch 21.0 mg, stearic acid 8.4 mg, tartaric acid 4.2 mg, silicon dioxide colloid 0.4 mg, hard gelatin capsule [titanium dioxide (E171), gelatin, indigocarmine (E132 )].

Dosage 180 mg

Active substance: temozolomide 180 mg.

Excipients: lactose 316.3 mg, sodium carboxymethyl starch 27.0 mg, stearic acid 10.8 mg, tartaric acid 5.4 mg, silicon dioxide colloid 0.5 mg, hard gelatin capsule [titanium dioxide (E171), gelatin, iron oxide dye yellow (E172)].

Dosage 250 mg

Active substance: Temozolomide 250 mg.

Excipients: lactose 154.3 mg, sodium carboxymethyl starch 22.5 mg, stearic acid 13.5 mg, tartaric acid 9.0 mg, silicon dioxide colloid 0.7 mg, hard gelatin capsule [titanium dioxide (E171), gelatin, dye sunset sunset yellow (E110)].

Description:

Dosage of 20 mg. Hard gelatin capsules №2 with a white body and a lid of green color.

Dosage 100 mg. Hard gelatin capsules No. 1 with a white body and a red lid.

Dosage 140 mg. Hard gelatin capsules No. 1 with a white body and a blue lid.

Dosage of 180 mg. Hard gelatin capsules No. 0 with a white body and a yellow lid.

Dosage of 250 mg. Hard gelatin capsules №0 with a white body and an orange lid.

The contents of the capsules are powder from white to light pink or light brown with a yellowish hue.

Pharmacotherapeutic group:An antitumour agent, an alkylating compound

ATX: & nbsp

L.01.A.X.03 Temozolomide

Pharmacodynamics:

Temozolomide is an imidazotetrazine alkylating drug with antitumor activity. After entering the blood stream at physiological pH values, it is rapidly biotransformed to the active compound - monomethyltriazenoimidazolecarboxamide (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, cytotoxic lesions resulting from this trigger the mechanism of aberrant reduction of the methyl residue.

Pharmacokinetics:

Temozolomide after ingestion is rapidly absorbed and is also rapidly excreted from the body with urine. Rapidly penetrates the blood-brain barrier (GEB) and enters the cerebrospinal fluid. The maximum concentration (C_mOh) in blood plasma is achieved on average 0.5-1.5 hours (the earliest - in 20 minutes) after taking the drug inside.

The half-life (T_1/2) from the blood plasma is approximately 1.8 hours. The clearance, the volume of distribution in the plasma and T_1/2do not depend on the dose. Temozolomide weakly binds to blood plasma proteins (12-16%). After oral administration of temozolomide, the average excretion rate with faeces for 7 days was 0.8%, indicating complete absorption of the drug. The main way to remove temozolomide is through the kidneys. At 24 hours after ingestion, approximately 5-10% of the dose is determined unchanged in the urine, the rest is excreted as 4-amino-5-imidazolecarboxamide hydrochloride (APC), temozolomidic acid or unidentified polar metabolites.

Taking temozolomide together with food causes a decrease in C_mOh by 33% and a decrease in the area under the concentration-time curve (AUC) by 9%.

The clearance of the drug in the blood plasma does not depend on age, kidney function or tobacco consumption. 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 tolerable dose (MTD) in children and adults was the same and was 1000 mg / m² for one course of treatment.

Indications:

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

- malignant glioma (glioblastoma multiforme or anaplastic astrocytoma), with relapse or disease progression after standard therapy;

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

Contraindications:

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

- severe myelosuppression;

- 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:

- Elderly age (over 70 years);

- impaired kidney function or liver of severe severity;

- intolerance to galactose, a deficiency of lactase or a syndrome of glucose-galactose malabsorption.

Pregnancy and lactation:

A drug Temozolomide 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 Temozolomide.

There is no information on excretion of temozolomide with breast milk, therefore during lactation it is necessary to stop breastfeeding or to cancel the drug Temozolomide.

Dosing and Administration:

A drug Temozolomide taken orally, on an empty stomach, at least 1 hour before meals. The prescribed dose should be taken using the lowest possible number of capsules. Capsules can not be opened or chewed, but should be swallowed whole, washed down with a glass of water.

The newly discovered multiform glioblastoma

Treatment of adult patients (over 18 years). Primary treatment conduct in combination with radiotherapy. A drug Temozolomide is applied in a dose 75 mg / m² daily for 42 days at the same time as 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 Temozolomide possibly throughout the 42-day period of combined treatment and up to 49 days, but only if all of the following conditions are met: absolute neutrophil count not lower than 1500 / μL (1.5 x 10⁹/ l), the number of platelets - not lower than 100000 / 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 drug cancellation Temozolomide during the combined phase of treatment are presented in Table 1.

Table 1. Recommendations for reducing the dose of shea drug cancellation Temozolomide when combined with radiotherapy

Criterion of toxicity	Break in the use of the drug Temozolomide *	Termination of the drug Temozolomide
Absolute number of neutrophils	≥ 500 / μL (≥ 0.5 x 10⁹/ l), but <1500 / μL (<1.5 × 10⁹/ l)	<500 / μL (<0.5 × 10⁹/ l)
Number of platelets	≥ 10000 / μL (≥ 10 × 10⁹/ l), but <100000 / μL (<100 × 10⁹/ l)	<10000 / μL (<10 × 10⁹/ l)
CTC (non-hematologic toxicity except for alopecia, nausea and vomiting)	Degree 2	Degree 3 or 4

* Use of the drug Temozolomide can be resumed if all of the following conditions are met: absolute neutrophil count not lower than 1500 / μL (1.5 × 10⁹/ l), the number of platelets - not lower than 100000 / μl (100 × 10⁹/ l), 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: a drug Temozolomide is prescribed at a dose of 150 mg / m for 5 days followed by a 23-day interruption in treatment.

Cycle 2: drug dose Temozolomide can be increased to 200 mg / m² (in accordance with the STS toxicity scale) did not exceed the grade 2 (except for alopecia, nausea and vomiting), while the absolute number of neutrophils was not lower than 1500 / μL (1, 5 x 10⁹/ l), and the number of platelets - not lower than 100000 / μL (100 × 10⁹/ l). If in cycle 2 the dose of the drug Temozolomide 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 the drug Temozolomide carry out 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 day 22 of treatment (21 days after taking the first dose of the drug Temozolomide) it is necessary to conduct a blood test with counting the number of cells. Abolition or reduction of the dose of the drug Temozolomide should be carried out, guided by Table 3.

Table 2. Dosage steps of the preparation Temozolomide with adjuvant therapy

Step	Dose (mg / m²/day)	Note
- 1	100	Reduction of dose taking into account 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 dose reduction or drug cancellation Temozolomide with adjuvant therapy

Criterion of toxicity	Reduce the dose of the drug Temozolomide 1 st stage (see Table 2)	Termination of the drug Temozolomide
Absolute number of neutrophils	<1000 / μL (<1.0 × 10⁹/ l)	*
Number of platelets	<50000 / μL (<50 × 10⁹/ l)	*
CTC (non-hematologic toxicity except for alopecia, nausea and vomiting)	Degree 3	Degree 4 *

* A drug Temozolomide 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 multiform glioblastoma or anaplastic astrocytoma (treatment of adults and children over 3 years old). Common metastatic malignant melanoma (treatment of adults)

Patients who had not previously received chemotherapy, the drug Temozolomide 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 can be increased to 200 mg / m²per day for 5 days, provided that on the first day of the next cycle the absolute amount 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 × 10⁹/ l).

Special patient groups

Children

A drug Temozolomide in children 3 years and older should be used only with recurrent or progressive malignant glioma. The experience of using the drug in children of this age group is very limited. Data on the use of the drug 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 with those in patients with mild or moderate hepatic insufficiency. Data on the dosage regimen of temozolomide in patients with severe hepatic insufficiency (class C) and renal insufficiency 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 Temozolomide in these patient groups.

Elderly patients

Based on the data obtained by the pharmacokinetic analysis method, in patients aged 19-78, 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 the drug Temozolomide in the treatment of progressive or recurrent malignant glioma or malignant melanoma

Begin the use of the drug Temozolomide can only be achieved with an absolute neutrophil count ≥ 1500 / μL (≥ 1.5 x 10⁹/ l) and platelets ≥ 100,000 / μL (≥ 100 x 10⁹/ 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 that day, then weekly until the absolute number of neutrophils is above 1500 / μL (1.5 x 10⁹/ l), and the number of platelets does not exceed 100,000 / μL (100 x 10⁹/ l). With an absolute neutrophil count below 1.0 x 10⁹/ l or platelets below 50 x 10⁹/ l 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 are signs of disease progression, the use of the drug Temozolomide should be discontinued.

Side effects:

Classification of the incidence of adverse events (WHO):

Often	> 1/10
often	from> 1/100 to <1/10
infrequently	from> 1/1000 to <1/100
rarely	from> 1/10000 to <1/1000
rarely	from <1/10000, including individual messages.

The newly discovered multiform glioblastoma (adult patients)

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 are listed below (the causal relationship between taking the drug and side effects has not been established).

Table 4.

System organism	Frequency development of side effects	The nature of the reaction
System organism	Frequency development of side effects	combined phase of treatment (with radiotherapy) n = 288	adjuvant phase of treatment n = 224
From the immune system	often	Candidiasis of the oral mucosa, herpes simplex, pharyngitis, wound infection, other infection.	Candidiasis of the oral mucosa, another infection;
From the immune system	infrequently		herpes simplex, herpes zoster, flu-like syndrome.
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, petechiae.
From the side of the cardiovascular system	often	edema, incl. peripheral edema, hemorrhage;	edema of the legs, hemorrhage, deep vein thrombosis;
From the side of the cardiovascular system	infrequently	palpitation, increased blood pressure, intracranial hemorrhage.	edema, incl. peripheral, thromboembolism of the pulmonary artery.
From the respiratory system	often	cough, shortness of breath;	cough, shortness of breath;
From the respiratory system	infrequently	pneumonia, upper respiratory tract infection, nasal congestion.	pneumonia, upper respiratory tract infection, sinusitis, bronchitis.
From the endocrine system	infrequently	syndrome Itenko-Cushing.	syndrome Itenko-Cushing.
From the skin and subcutaneous tissue, mammary glands	Often	alopecia, rash;	alopecia, rash;
	often	dermatitis, dry skin, erythema, skin itching, face swelling;	dry skin, itching of the skin;
	infrequently	photosensitivity reaction, pigmentation disorder, exfoliation.	erythema, impaired pigmentation, excessive sweating, pain in the mammary glands, swelling of the face.
From the nervous system	Often	headache;	headache, convulsions;
From the nervous system	often	anxiety, emotional lability, insomnia, dizziness, aphasia, balance disorder, impaired concentration, confusion and impaired consciousness, convulsions, memory impairment, neuropathy, paresthesia, drowsiness, speech disorder, tremor;	anxiety, depression, emotional lability, insomnia, dizziness, aphasia, imbalance, impaired concentration, confusion, dysphasia, speech disorder, hemiparesis, memory impairment, neurological disorders (unspecified), neuropathy, paresthesia, drowsiness, tremor;
From the respiratory system	often	cough, shortness of breath;	cough, shortness of breath;
From the respiratory system	infrequently	pneumonia, upper respiratory tract infection, nasal congestion.	pneumonia, upper respiratory tract infection, sinusitis, bronchitis.
From the endocrine system	infrequently	syndrome Itenko-Cushing.	syndrome Itenko-Cushing.
From the skin and subcutaneous tissue, mammary glands	Often	alopecia, rash;	alopecia, rash;
	often	dermatitis, dry skin, erythema, skin itching, face swelling;	dry skin, itching of the skin;
	infrequently	photosensitivity reaction, pigmentation disorder, exfoliation.	erythema, impaired pigmentation, excessive sweating, pain in the mammary glands, swelling of the face.
From the nervous system	Often	headache;	headache, convulsions;
	often	anxiety, emotional lability, insomnia, dizziness, aphasia, balance disorder, impaired concentration, confusion and impaired consciousness, convulsions, memory impairment, neuropathy, paresthesia, drowsiness, speech disorder, tremor;	anxiety, depression, emotional lability, insomnia, dizziness, aphasia, imbalance, impaired concentration, confusion, dysphasia, speech disorder, hemiparesis, memory impairment, neurological disorders (unspecified), neuropathy, paresthesia, drowsiness, tremor;
	infrequently	agitation, apathy, behavioral disorders, depression, hallucinations, impaired perception, extrapyramidal disorders, dysphasia, ataxia, gait disorders, hemiparesis, hyperesthesia, hypoesthesia, neurological disorders (unspecified), epileptic status, parasymia, thirst.	hallucinations, ataxia, impaired coordination, amnesia, gait disorders, hemiplegia, hyperesthesia, impaired sensory organs.
From the side of the musculoskeletal system	often	arthralgia, muscle weakness;	arthralgia, musculoskeletal pain, myalgia, muscle weakness;
From the side of the musculoskeletal system	infrequently	pain in the back, musculoskeletal pain, myalgia, myopathy.	back pain, myopathy.
From the side of the organ of vision	often	blurred vision;	blurred vision, diplopia, limitation of visual fields;
From the side of the organ of vision	infrequently	pain in the eyes, hemianopsia, visual impairment, decreased visual acuity, limitation of visual fields.	pain in the eyes, dry eyes, decreased visual acuity.
From the genitourinary system	often	frequent urination, urinary incontinence;	urinary incontinence;
From the genitourinary system	infrequently	impotence.	dysuria, amenorrhea, menorrhagia, vaginal bleeding, vaginitis.
From the side of the hearing and vestibular system	often	hearing loss;	hearing loss, ringing in the ears;
From the side of the hearing and vestibular system	infrequently	pain in the ears, hyperacia, ringing in the ears, otitis media.	deafness, pain in the ears, dizziness.
From the digestive system	Often	anorexia, constipation, nausea, vomiting;	anorexia, constipation, nausea, vomiting;
	often	increased ALT activity, hyperglycemia, weight loss, abdominal pain, diarrhea, dyspepsia, dysphagia, stomatitis, a taste disorder;	increased ALT activity, weight loss, diarrhea, dyspepsia, dysphagia, stomatitis, dryness of the oral mucosa, impaired taste;
	infrequently	hypokalemia, increased alkaline phosphatase activity, weight gain, discoloration of the tongue, increased gamma-GT activity, ACT, liver enzymes.	hyperglycemia, weight gain, bloating, fecal incontinence, hemorrhoids, gastroenteritis, dental diseases.
Other	Often	fatigue;	fatigue;
	often	fever, pain syndrome, radiation damage, allergic reaction;	fever, pain syndrome, radiation damage, allergic reaction;
	infrequently	sensation of "hot flashes" of heat to the body, asthenia, malaise, chills.	asthenia, malaise, 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)

The following undesirable phenomena noted with the administration of temozolomide.

On the part of the hematopoiesis system:

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 and / or removal of temozolomide 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.

From the digestive system:

Often - nausea, vomiting, constipation, anorexia;

often - diarrhea, abdominal pain, dyspepsia, taste perversion.

The most frequent were nausea and vomiting.In most cases, these events were 1-2 (from mild to moderate) severity and were treated independently or were easily controlled with standard antiemetic therapy. The frequency of severe nausea and vomiting is 4%.

From the nervous system:

very often - headache;

often - drowsiness, dizziness, paresthesia, asthenia.

From the skin and skin appendages:

often - rash, itching, alopecia, petechiae;

rarely - urticaria, exanthema, erythroderma.

Other:

Often - increased fatigue;

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

rarely - opportunistic infections, including pancytopenia;

rarely - angioedema.

Post-registration research data

During post-registration studies, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, and allergic reactions, including anaphylaxis, were very rare.

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

Cases of opportunistic infection were rarely reported, including pneumonia caused by Pneumocystis carinii, and cases of primary and reactivated cytomegalovirus infection. Cases of reactivation of the hepatitis B virus have been described, including some fatal cases (see section "Special instructions").

Very rarely reported cases of interstitial pneumonitis / pneumonitis and pulmonary fibrosis.

Also very rarely observed myelodysplastic syndrome, secondary malignant processes, including myeloid leukemia.

There have been reports of prolonged pancytopenia, which could result in aplastic anemia, which in some cases resulted in death.

There were also cases of diabetes insipidus.

Overdose:

Symptoms. When the drug is used in doses of 500, 750, 1000 and 1250 mg /m² (the total dose received over a 5-day treatment cycle), the dose-limiting toxic effects were changes in blood that were noted at any dose but more pronounced at higher doses. A case of overdose (taking a dose of 2000 mg per 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 side effects, hematopoietic oppression was observed, complicated or uncomplicated by the infection, in some cases prolonged and severe, with a fatal outcome.

Treatment. Antidote to the drug Temozolomide not known. It is recommended hematological control and, if necessary, symptomatic therapy.

Interaction:

Taking temozolomide simultaneously with ranitidine does not lead to a clinically significant change in the degree of absorption of temozolomide.

Simultaneous application of temozolomide with dexamethasone, prochlorperazine, phenytoin, carbamazepine, ondansetron, antagonists of H₂-gistaminovyh receptors or phenobarbital does not change the clearance of temozolomide.

Simultaneous use of temozolomide with valproic acid results in a weak but statistically significant decrease in the clearance of temozolomide.

Studies aimed at studying the effect 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 blood plasma proteins, its effect on the pharmacokinetics of other drugs is unlikely.

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

Children. The interaction was studied only in adults.

Special instructions:

Hepatic and renal insufficiency

The pharmacokinetics of temozolomide in patients with normal liver function and in patients with impaired liver function of mild or moderate severity are comparable.

Data on the use of the drug Temozolomide in patients with severe hepatic impairment (Child-Pugh class III) or renal dysfunction is not available. Based on 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 the drug is administered Temozolomide such patients should be cautious.

It was also reported on the development of hepatitis due to the reactivation of viral hepatitis B, which in some cases led to a lethal outcome. Before starting treatment, patients should undergo a screening test for the presence of a viral hepatitis B infection.Patients with signs of a previous infection with viral hepatitis B should be observed to identify clinical and laboratory signs of hepatitis or the reactivation of hepatitis B virus during treatment and for several months after treatment with the drug Temozolomide. Therapy should be discontinued in patients with signs of active infection with viral hepatitis B.

Antiemetic therapy

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 the background of the drug Temozolomide there is nausea or vomiting, with subsequent administration it is recommended to carry out antiemetic therapy. Antiemetic drugs can be taken both before and after taking the drug Temozolomide. Even if vomiting developed within the first 2 hours after taking the drug Temozolomide, repeat the reception of the drug on the same day should not be.

Pneumonia caused by Pneumocystis carinii

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 durations of drug use Temozolomide, increased alertness to the possible development of PCP should be shown for all patients receiving the drug Temozolomide, especially in combination with glucocorticosteroids.

Elderly patients

In elderly people (over 70 years), the risk of developing neutropenia and thrombocytopenia is higher than in younger patients. For such patients, the drug Temozolomide should be administered with caution.

Children

Temozolomide has not been studied in children under the age of 3 with multiform glioblastoma and in children under the age of 18 with malignant melanoma. Experience with temozolomide in children older than 3 years with glioma is limited.

Men and women of reproductive age during the use of the drug Temozolomide and at least 6 months after the end of the drug should use reliable methods of contraception.

Because of the risk of irreversible infertility in the background of drug treatment Temozolomide male patients before the start of treatment, if necessary, it is recommended to discuss the possibility of cryopreservation of sperm.

If the contents of the capsule (powder) get on the skin or mucous membranes, they should be washed with a large amount of water.

Specific information on certain components of the drug

Temozolomide contains lactose. Patients with rare hereditary diseases, including galactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome, should be careful when using the drug Temozolomide.

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

Some side effects of the drug Temozolomide, 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.

Form release / dosage:

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

Packaging:

For 5 or 20 capsules in a glass bottle of brown glass, ukuporenny lid.

Each bottle, together with the instructions for use, is placed in a pack of cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 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-004068

Date of registration:10.01.2017

Expiration Date:10.01.2022

The owner of the registration certificate:NewVac, Inc.NewVac, Inc. Russia

Manufacturer: & nbsp

Research Institute of Chemical Diversity, JSC Russia

Representation: & nbspResearch Institute of Chemical Diversity, JSCResearch Institute of Chemical Diversity, JSCRussia

Information update date: & nbsp29.01.2017

Illustrated instructions

Instructions

Temozolomide (Temozolomide)