Composition, form of production and packaging
Capsules size 3, with an opaque lid green and a white body; on the capsules with black ink inscriptions: on the lid - "TEMODAL", on the body - "5 mg", trademark in the form of stylized letters "SP" and two strips; the contents of the capsules - powder from white to light pink or light yellow-brown color.
1 caps.
temozolomide 5 mg
[PRING] lactose - 132.8 mg, sodium carboxymethyl starch - 7.5 mg, silicon dioxide colloid - 0.2 mg, tartaric acid - 1.5 mg, stearic acid - 3 mg.
The composition of the capsule shell: titanium dioxide - 1.093 mg, indigocarmine - 0.001 mg, iron oxide oxide yellow - 0.059 mg, sodium lauryl sulfate - 0.07 mg, gelatin - qs
Composition of ink for inscription: black dye (shellac, ethanol *, isopropanol *, butanol *, propylene glycol, purified water *, ammonia water *, potassium hydroxide, iron dye oxide black).
5 pieces. - bottles of dark glass (1) - cardboard boxes.
20 pcs. - bottles of dark glass (1) - cardboard boxes.
1 PC. - Sachets from aluminum foil (5) - cardboard boxes.
1 PC. - Sachets from aluminum foil (20) - cardboard boxes.
Capsules of size No. 2, with an opaque yellow lid and a white body; on the capsules with black ink inscriptions: on the lid - "TEMODAL", on the body - "20 mg", a trademark in the form of stylized letters "SP" and two strips; the contents of the capsules - powder from white to light pink or light yellow-brown color.
1 caps.
temozolomide 20 mg
[PRING] lactose - 182.2 mg, sodium carboxymethyl starch - 11 mg, silicon dioxide colloid - 0.2 mg, tartaric acid - 2.2 mg, stearic acid - 4.4 mg.
The composition of the capsule shell: titanium dioxide - 1.174 mg, iron oxide, yellow oxide - 0.217 mg, sodium lauryl sulfate - 0.088 mg, gelatin - qs
Composition of ink for inscription: black dye (shellac, ethanol *, isopropanol *, butanol *, propylene glycol, purified water *, ammonia water *, potassium hydroxide, iron dye oxide black).
5 pieces. - bottles of dark glass (1) - cardboard boxes.
20 pcs. - bottles of dark glass (1) - cardboard boxes.
1 PC. - Sachets from aluminum foil (5) - cardboard boxes.
1 PC. - Sachets from aluminum foil (20) - cardboard boxes.
Capsules of size 1, with an opaque cap of pink color and a white body; on the capsules with black ink inscriptions: on the lid - "TEMODAL", on the body - "100 mg", a trademark in the form of stylized letters "SP" and two strips; the contents of the capsules - powder from white to light pink or light yellow-brown color.
1 caps.
temozolomide 100 mg
[PRING] lactose - 175.7 mg, sodium carboxymethyl starch - 15 mg, silicon colloidal dioxide - 0.3 mg, tartaric acid - 3 mg, stearic acid - 6 mg.
The composition of the capsule shell: titanium dioxide - 2.16 mg, iron oxide red oxide - 0.029 mg, sodium lauryl sulfate - 0.106 mg, gelatin - qs
Composition of ink for inscription: black dye (shellac, ethanol *, isopropanol *, butanol *, propylene glycol, purified water *, ammonia water *, potassium hydroxide, iron dye oxide black).
5 pieces. - bottles of dark glass (1) - cardboard boxes.
20 pcs. - bottles of dark glass (1) - cardboard boxes.
1 PC. - Sachets from aluminum foil (5) - cardboard boxes.
1 PC. - Sachets from aluminum foil (20) - cardboard boxes.
Capsules of size в„–0, with a transparent lid of blue color and opaque case of white color; on the capsules with black ink inscriptions: on the lid - "TEMODAL", on the body - "140 mg", trademark in the form of stylized letters "SP" and two strips; the contents of the capsules - powder from white to light pink or light yellow-brown color.
1 caps.
temozolomide 140 mg
[PRING] lactose - 246 mg, sodium carboxymethyl starch - 21 mg, silicon dioxide colloid - 0.4 mg, tartaric acid - 4.2 mg, stearic acid - 8.4 mg.
The composition of the capsule shell: titanium dioxide - 1.827 mg, indigocarmine - 0.028 mg, sodium lauryl sulfate - 0.138 mg, gelatin - qs
Composition of ink for the inscription: dye black (shellac, ethanol *, isopropanol *, butanol *, propylene glycol, purified water *, ammonia water *, potassium hydroxide, iron oxide ferrous oxide).
5 pieces. - bottles of dark glass (1) - cardboard boxes.
20 pcs. - bottles of dark glass (1) - cardboard boxes.
1 PC. - Sachets from aluminum foil (5) - cardboard boxes.
1 PC. - Sachets from aluminum foil (20) - cardboard boxes.
Capsules of size в„–0, with an opaque lid of red-brown color and a body of white color; on the capsules with black ink inscriptions: on the lid - "TEMODAL", on the body - "180 mg", trademark in the form of stylized letters "SP" and two strips; the contents of the capsules - powder from white to light pink or light yellow-brown color.
1 caps.
temozolomide 180 mg
[PRING] lactose - 316.3 mg, sodium carboxymethyl starch - 27 mg, silicon dioxide colloid - 0.5 mg, tartaric acid 5.4 mg, stearic acid 10.8 mg.
The composition of the shell of the capsule: titanium dioxide - 1.921 mg, iron oxide oxide yellow - 0.115 mg, iron oxide red oxide - 0.402 mg, sodium lauryl sulfate - 0.137 mg, gelatin - qs
Composition of ink for the inscription: dye black (shellac, ethanol *, isopropanol *, butanol *, propylene glycol, purified water *, ammonia water *, potassium hydroxide, iron oxide ferrous oxide).
5 pieces. - bottles of dark glass (1) - cardboard boxes.
20 pcs. - bottles of dark glass (1) - cardboard boxes.
1 PC. - Sachets from aluminum foil (5) - cardboard boxes.
1 PC. - Sachets from aluminum foil (20) - cardboard boxes.
Capsules of size No. 0, with an opaque lid and a white body; on the capsules with black ink inscriptions: on the lid - "TEMODAL", on the body - "250 mg", a trademark in the form of stylized letters "SP" and two strips; the contents of the capsules - powder from white to light pink or light yellow-brown color.
1 caps.
temozolomide 250 mg
[PRING] lactose - 154.3 mg, sodium carboxymethyl starch - 22.5 mg, silicon dioxide colloid - 0.7 mg, tartaric acid - 9 mg, stearic acid - 13.5 mg.
The composition of the capsule shell: titanium dioxide - 3.045 mg, sodium lauryl sulfate - 0.136 mg, gelatin - qs
Composition of ink for inscription: black dye (shellac, ethanol *, isopropanol *, butanol *, propylene glycol, purified water *, ammonia water *, potassium hydroxide, iron dye oxide black).
5 pieces. - bottles of dark glass (1) - cardboard boxes.
20 pcs. - bottles of dark glass (1) - cardboard boxes.
1 PC. - Sachets from aluminum foil (5) - cardboard boxes.
1 PC. - Sachets from aluminum foil (20) - cardboard boxes.
* - removed during production.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
PHARMACHOLOGIC EFFECT
An antineoplastic agent, an imidazotetrazine derivative, is an alkylating agent. When entering the systemic blood stream, at physiological values, the pH undergoes 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 at the O 6 position and additional alkylation at the N 7 position. Apparently, cytotoxic lesions resulting from this include (trigger) the mechanism of aberrant reduction of the methyl residue.
PHARMACOKINETICS
Suction
After oral administration, temozolomide is rapidly absorbed. C max in plasma is achieved on average 0.5-1.5 h (at the earliest - 20 min) after taking the drug. Taking Temodal В® along with food causes a decrease in C max by 33% and a decrease in AUC by 9%. After oral administration of TemodalВ®, the average excretion rate with feces for 7 days was 0.8%, indicating complete absorption of the drug.
Distribution
Temozolomide quickly penetrates the BBB and enters the cerebrospinal fluid.
V d does not depend on the dose. Temozolomide weakly binds to proteins (12-16%).
Excretion
Quickly excreted from the body with urine. T 1/2 from the plasma is approximately 1.8 hours. The main way of removal of temozolomide is the kidney. At 24 hours after ingestion, approximately 5-10% of the 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. Clearance and T 1/2 are dose independent.
Pharmacokinetics in special clinical cases
The clearance of the drug in plasma does not depend on age, kidney function or smoking.
Pharmacokinetic profile of the drug in patients with impaired liver function of mild or moderate degree is the same as in persons with normal liver function.
In children, AUC is higher than in adults.
The maximum tolerated dose in children and adults was the same and amounted to 1000 mg / m 2 per treatment cycle.
INDICATIONS
- newly diagnosed 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 metastasizing malignant melanoma - as a therapeutic tool of the first series.
DOSING MODE
Temodal В® is taken orally, on an empty stomach, no 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 adult patients older than 18 years)
Primary treatment is carried out in combination with radiotherapy . Temodal В® is prescribed at a dose of 75 mg / m 2 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: absolute neutrophil count not lower than 1500 / ОјL, platelet count - not less than 100,000 / ОјL, 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 withdrawal of Temodal В®during the combined phase of treatment are given in Table 1.
Table 1. Recommendations for dose reduction or withdrawal of Temodal В® in combination treatment with radiotherapy
Criterion of toxicity Break in taking Temodal В® * Stopping Temodal В®
the absolute number of neutrophils is? 500 / Ојl, but <1500 / Ојl? 500 / ОјL
the platelet count is 10,000 / ОјL, but <100,000 / ОјL <10,000 / ОјL
STS of non-hematological toxicity (except for alopecia, nausea and vomiting) Degree 2 Degree 3 or 4
* Resumption of Temodal В® is possible if all of the following conditions are met: absolute neutrophil count not lower than 1500 / Ојl, platelet count - not lower than 100,000 / Ојl, total toxicity criterion (CTC) not higher than degree 1 (except for alopecia, nausea and vomiting).
Adjuvant therapy is prescribed 4 weeks after the completion of the combination therapy and is performed in the form of 6 additional cycles.
Cycle 1: Temodal В® is administered at a dose of 150 mg / m 2 for 5 days followed by a 23-day interruption in treatment.
Cycle 2: The dose of Temodal В® can be increased to 200 mg / m 2 / day, provided that during the first cycle, the severity of non-hematologic toxicity (according to 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 / Ојl, and the number of platelets was not lower than 100,000 / ОјL. If the dose of Temodal В® 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 2 , in the same daily dose the drug is administered in the following cycles (in the absence of toxicity). In each cycle, the preparation Temodal В® 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 (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 the drug should be carried out, guided by Table 3.
Table 2. Dosage levels of TemodalВ® with adjuvant therapy
Step Dose (mg / m 2 / day)
-1 100 Reduction of dose taking into account previous toxicity (see Table 3)
0 150 Dose during cycle 1
1 200 Dose during cycles 2-6 (in the absence of toxicity)
Table 3. Recommendations for dose reduction or withdrawal of Temodal В® with adjuvant therapy
Toxicity criterion To reduce the dose of Temodal В® by 1 step (see Table 2) Termination of Temodal В®
absolute number of neutrophils <1000 / ОјL *
number of platelets <50 000 / ОјL *
STS of non-hematological toxicity (except for alopecia, nausea and vomiting) Degree 3 Degree 4 *
* Temodal В® should be discontinued if a dose reduction of <100 mg / m 2 is required, as well as in the case of recurrence of non-hematologic toxicity grade 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 undergone chemotherapy, Temodal В® were prescribed at a dose of 200 mg / m 2 1 time / 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 2 once / day; in the second cycle, the dose may be increased to 200 mg / m 2 / day, provided that on the first day of the next cycle the absolute number of neutrophils is not lower than 1500 / Ојl, and the platelet count is not lower than 100,000 / Ојl.
Recommendations for modifying the dose of Temodal В® in the treatment of progressive or recurrent malignant glioma or malignant melanoma
To start treatment with Temodal ® is possible only with an absolute number of neutrophils ≤ 1500 / μL and platelets ≥ 100,000 / μL, Complete clinical blood test should be performed on day 22 (21 days after the first dose), but no later than 48 h after this day; further - weekly, until the absolute number of neutrophils is higher than 1500 / μL, and the number of platelets does not exceed 100,000 / μl. With an absolute number of neutrophils 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 / m 2 , 150 mg / m 2 and 200 mg / m 2 . The minimum recommended dose is 100 mg / m 2 .
Duration of treatment is maximum 2 years. When there is a progression of the disease, the drug should be discontinued.
SIDE EFFECT
The newly discovered multiform glioblastoma (adult patients)
The table 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 (the causal relationship between taking the drug and side effects has not been established). Determination of the frequency of adverse reactions: very often (> 10%), often (> 1%, <10%), infrequently (> 0.1%, <1%).
Reaction frequency Response pattern
combined treatment phase (with radiotherapy) n = 288 adjuvant treatment phase n = 224
Mechanisms of resistance to infections
often oral candidiasis, herpes simplex, pharyngitis, wound infection, other oral candidiasis infection, other infection
infrequently - herpes simplex, herpes zoster, influenza-like symptoms
On the part of the hematopoiesis system
often leukopenia, lymphopenia, neutropenia, thrombocytopenia anemia, febrile neutropenia, leukopenia, thrombocytopenia
infrequently anemia, febrile neutropenia of lymphopenia, petechiae
From the side of the cardiovascular system
often swelling, t.ch. swelling of the legs, hemorrhage, edema of the legs, hemorrhage, deep vein thrombosis
infrequently palpitation, arterial hypertension, cerebral hemorrhage edema, t.ch. peripheral edema, pulmonary embolism
From the respiratory system
often cough, dyspnea cough, dyspnea
infrequently pneumonia, upper respiratory infection, nasal congestion of pneumonia, upper respiratory tract infections, sinusitis, bronchitis
From the endocrine system
infrequently cushingoid cushingoid
From the nervous system
very often headache headache, cramps
anxiety, emotional lability, insomnia, dizziness, balance disorder, impaired concentration, confusion and decreased consciousness, convulsions, memory impairment, neuropathy, paresthesia, drowsiness, speech disorder, tremor anxiety, depression, emotional lability, insomnia, dizziness, balance disorder, impaired concentration, confusion, speech disorder, hemiparesis, memory impairment, neurological disorders (unspecified), neuropathy, paresthesia, drowsiness, tremor
infrequent apathy, behavioral disorders, depression, hallucinations, impaired perception, extrapyramidal disorders, gait disorders, hemiparesis, hyperesthesia, hypoesthesia, neurological disorders (unspecified), epileptic status, parosmia, thirst for hallucinations, amnesia, gait disturbance, hemiplegia, hyperesthesia, sensory side
From the skin and subcutaneous tissue, mammary glands
very often alopecia, rash, alopecia, rash
often dermatitis, dry skin, erythema, itching, swelling, dry skin, pruritus
infrequently photosensitivity, pigmentation disorders, exfoliation erythema, pigmentation disorders, increased sweating, pain in the breast, face edema
From the musculoskeletal system
often arthralgia, muscle weakness arthralgia, muscle weakness, myalgia, musculoskeletal pain
uncommon back pain, musculoskeletal pain, myalgia, myopathy, back pain, myopathy
part of the vision
is often blurred vision blurred vision, diplopia, restriction ix fields of
rare eye pain, hemianopsia, blurred vision, decreased visual acuity, visual field restriction eye pain, dry eyes, blurred vision
From the hearing and vestibular system
often worsening hearing loss of hearing, tinnitus
rare ear pain, hyperacusis, otitis media, ringing in deaf ears, ear pain, vertigo
on the part of the digestive system
often anorexia, constipation, nausea, vomiting, anorexia , constipation, nausea, vomiting
often increased ALT, abdominal pain, diarrhea, dyspepsia, dysphagia, stomatitis, taste disturbance increased ALT, diarrhea, dyspepsia, dysphagia, stomatitis, dry mouth, taste disturbance
infrequently increase of alkaline phosphatase activity, change the language of color, increased GGT activity, ACT, liver enzymes, abdominal distension, fecal incontinence, hemorrhoids, gastroenteritis, tooth disease
Urinary system
frequent urination, urinary incontinence
rarely - dysuria
part of the reproductive system
rarely impotence amenorrhea, menorrhagia, vaginal hemorrhage, vaginitis
part of metabolism
often hyperglycemia, weight loss, weight loss
rarely hypokalemia, weight gain, hyperglycemia, weight gain
On the part of the body as a whole
is often fatigue fatigue
often fever, pain syndrome, radiation damage, allergic reaction to fever, pain syndrome, radiation injury, al- ergic reaction
rarely hot flashes, fatigue, deterioration, chills, fatigue, deterioration, chills
Laboratory findings:myelosuppression (neutropenia and thrombocytopenia) is a dose-limiting side effect. Among the patients of both groups (with combination therapy and adjuvant) changes of grade 3 and 4 by neutrophils, including neutropenia, observed in 8% of cases, and from the platelets, including thrombocytopenia, - in 14% of cases.
Progressive or recurrent malignant glioma (adults and children older than 3 years) or malignant melanoma (adults)
Determining the frequency of adverse reactions: very common (10%?), Often (1%, <10%?), Infrequent (0.1%? , <1%), rare (? 0.01%, <0.1%) and very rare (<0.01%).
From hemopoiesis system:very often - thrombocytopenia, neutropenia, lymphopenia; rarely - pancytopenia, leukopenia, anemia. In the treatment of patients with metastatic melanoma and glioma were observed cases of thrombocytopenia and neutropenia grade 3 or 4 at 19% and 17%, respectively - in glioma and 20% and 22%, respectively - in melanoma. Hospitalization of the patient and / or removal of the drug Temodal В® thus required to 8% and 4%, respectively in glioma and 3% and 1.3% - melanoma. Bone marrow suppression is usually developed during the first few cycles of treatment, with a maximum between 21 and 28 days; recovery was usually within 1-2 weeks. Evidence of cumulative myelosuppression was observed.
From the digestive system:very often - nausea, vomiting, anorexia, constipation; often - diarrhea, abdominal pain, dyspepsia, taste perversion. The most common are nausea and vomiting. In most cases, these phenomena were 1-2 (mild to moderate) degree and passed alone or easily monitored by standard antiemetic therapy. The frequency of severe nausea and vomiting - 4%.
From the nervous system: very often - headache; often - drowsiness, dizziness, paresthesia, asthenia.
Skin and skin appendages: often - a rash, itching, alopecia, petechiae; very rarely - urticaria, rash, erythroderma, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome.
Immune system:very rare - allergic reactions, including anaphylaxis.
Other: often - fatigue; often - weight loss, dyspnea, fever, chills, malaise; rarely - opportunistic infections, including pneumonia caused by Pneumocystis carinii; very rarely mentioned the development of myelodysplastic syndrome and secondary malignancies, including leukemia, and also noted the development of prolonged pancytopenia with the risk of aplastic anemia and irreversible infertility.
CONTRAINDICATIONS
- severe myelosuppression;
- Pregnancy;
- the period of lactation (breastfeeding);
- Children up to age 3 years (recurrent or progressive malignant glioma) or 18 years (for the first time revealed glioblastoma multiforme or malignant melanoma);
- rare hereditary disorders such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption;
- hypersensitivity to temozolomide or other components of the drug, as well as dacarbazine.
With care should be prescribed to patients older than 70 years, with severe renal or hepatic insufficiency.
PREGNANCY AND LACTATION
Contraindicated in pregnancy and lactation (breastfeeding).
Men and women of childbearing age during treatment with Temodal В® , and at least for 6 months after the end of the need to use reliable methods of contraception.
Because of the risk of irreversible infertility on the background of treatment with Temodal В® male patients before treatment, if necessary, it is recommended to discuss the possibility of sperm cryopreservation.
APPLICATION FOR FUNCTIONS OF THE LIVER
With care should be prescribed in severe renal insufficiency.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With care should be prescribed in severe liver disease.
APPLICATION FOR CHILDREN
Contraindications: Children under 3 years (recurrent or progressive malignant glioma) or 18 years (for the first time revealed glioblastoma multiforme or malignant melanoma).
APPLICATION IN ELDERLY PATIENTS
With care should be prescribed to patients older than 70 years.
SPECIAL INSTRUCTIONS
Conducting prophylactic antiemetic therapy is recommended before the start of the combined treatment (radiotherapy) and is strongly recommended during adjuvant therapy in newly diagnosed glioblastoma multiforme. If during the treatment preparation Temodal В® nausea or vomiting on subsequent receptions recommended antiemetic therapy. Antiemetics may be taken both before and after taking the drug Temodal В® . Even if vomiting developed in the first 2 hours after administration of the drug Temodal В® repeat the drug on the same day follows.
Due to an increased risk of pneumonia caused by Pneumocystis carinii, in patients receiving combination therapy with radiation therapy for 42 days (up to 49 days), so patients are advised to conduct preventive treatment against the pathogen Pneumocystis carinii. Although more frequent development of pneumonia caused by Pneumocystis carinii, is associated with a longer period of treatment with Temodal В® , increased vigilance in regard to the possible development of PCP should be exercised in respect of all patients receiving Temodal В® , particularly in combination with corticosteroids.
Pharmacokinetic parameters of the drug Temodal В®in subjects with normal hepatic function and in patients with impaired hepatic function or mild to moderate in severity closely comparable. Data on the use Temodal drug В® patients with severe hepatic impairment (class C Child-Pugh) or impaired renal function is not available. On the basis of the pharmacokinetic properties Temodal data it seems unlikely that even patients with severe liver or kidney function may require a reduction in dose. Nevertheless, the appointment of the drug Temodal В® in such patients should exercise caution.
After contact with the capsule contents (powder) to the skin or mucous membrane must be washed with plenty of water.
Effects on ability to drive vehicles and management of vehicle
Some side effects of the drug such as drowsiness and fatigue, may adversely affect the ability to drive vehicles or perform potentially hazardous activities that require high concentration and psychomotor speed reactions.
OVERDOSE
When using the drug in doses of 500 mg / m 2 , 750 mg / m 2 1000 mg / m 2 and 1,250 mg / m 2 (total dose received over a 5-day treatment cycle) dose-limiting toxicity was hematologic toxicity that was observed when receiving any dose, but more pronounced - at higher doses. A case of an overdose (reception dose of 2 g / day for 5 days) which resulted in the developed pancytopenia, pyrexia, multiple organ failure and death. When receiving the drug for more than 5 days (up to 64 days), among other side effects observed inhibition of hematopoiesis, complicated or not complicated by infection, in some cases, long and expressed, with a fatal outcome.
Treatment: An antidote is not known. Haematological monitoring is recommended, and if necessary - symptomatic therapy.
DRUG INTERACTION
Receiving Temodal preparation В® conjunction with ranitidine does not lead to clinically meaningful change in the degree Temodal suction.
Co-administration of dexamethasone, prochlorperazine, phenytoin, carbamazepine, ondansetron, blockers of histamine H 2 -receptors or phenobarbital not alter the clearance of temozolomide.
Co-administration with valproic acid is poorly marked, but statistically significant decrease in clearance of temozolomide.
Research aimed at clarifying the effects of temozolomide on the metabolism and excretion of other drugs have been conducted. Due to the fact that temozolomide is not metabolized in the liver, and weakly binds to the protein, its effect on the pharmacokinetics of other drugs are unlikely.
Application Temodal preparation В® together with other substances depressing the bone marrow may increase the likelihood of myelosuppression.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be kept out of reach of children at a temperature of from 2 В° to 30 В° C. Shelf life - 3 years.
