Temodal

Temodal has anti-tumor properties.

Indications Temodal

It is used to eliminate such pathologies:

• multiform glioblastoma, which was diagnosed for the first time. In this case, the drug should be used in conjunction with radiotherapy procedures, and in addition to the need for supporting activities;
• glioma malignant - to eliminate the recurrence of this disease, or in its progression even in the case of standard medical procedures;
• melanoma, which develops as a metastasizing malignant neoplasm of a widespread nature. Temodal is used as the main medicine.

[1], [2]

Release form

Release of the medication occurs in capsules with a volume of 5 and 20 mg, and in addition 0.1, 0.14, 0.18 and 0.25 grams - 5 capsules inside the blister, 4 blisters inside the box.

Also produced in the form of powder, from which the solution is made - in vials of 0.1 g capacity.

[3], [4]

Pharmacodynamics

Entered into the circulatory system, the active element of the drug is subjected to a process of rapid conversion of a non-enzymatic character (at physiological pH values) - it is transformed into an active compound of MTIC. It is believed that the cytotoxicity of this element is due to the fact that DNA undergoes alkylation processes.

Guanine alkylation is often carried out in the O6 positions, as well as N7. These data allow us to conclude that the cytotoxic damage resulting from this process develops as an activator of the reducing activity of the methyl residue.

[5], [6], [7], [8], [9]

Pharmacokinetics

Absorption.

Temozolomide at high speed and almost completely absorbed, reaching the level of Cmax after a lapse of 1 hour (on average). Food reduces the degree and speed of suction of the element. The mean values of Cmax inside the plasma are reduced by 32%, and the period of action of the active component is doubled (from 1 to 2.25 hours). A similar effect is noted with the use of drugs immediately after a hearty breakfast, which included fatty foods, which also contain a large number of carbons.

Distribution processes.

The distribution volume of temozolomide is 0.4 l / kg (with% CV = 13%). Synthesis with intracellular protein is very weak. The average value of the total radioactivity of the substance is 15%.

Exchange processes.

The hydrolysis of the substance is carried out spontaneously (if the pH is physiological), before the formation of active species, MTIC, and the decomposition product - temozolomide acids. MTIC is then hydrolyzed to the element of 5-amino-imidazole-4-carboxamide (APC), which is an intermediate component of nucleic acid biosynthesis with purine, as well as methylhydrazine. Elements of hemoprotein P450 are not important participants in the metabolism of temozolomide and MTIC. Regarding the ATS of temozolomide, the effect of MTCR with AIC is 2.4%, respectively, and 23%, respectively.

Excretion.

Approximately 38% of the used temozolomide from the total radioactive portion is excreted over the interval of the first week: by 37.7% together with urine, and by 0.8% - with feces.

The excretion period of the active element from the plasma is slightly less than 120 minutes. Most of the medication is excreted by the kidneys. One day after consumption, approximately 10% of temozolomide is excreted in the urine. This component can also be derived as polar decomposition products, which can not be identified. The clearance values and the half-life do not vary with the size of the portion.

[10], [11], [12], [13],

Dosing and administration

The drug should be consumed in a dosage of 75 mg / m ² once daily for a period of 42 days, in conjunction with the implementation of concomitant radiotherapy (at a total dosage of 60 Gy, the number of injections is 30 sessions).

Interrupt the course of drug use is not possible, although occasionally this action can be prescribed by the treating doctor (if the patient has stable negative manifestations). If the drug was stopped, therapy should be resumed during the 42-day attendant segment, although it can stretch out to 49 days, subject to all the conditions described below:

• the absolute neutrophil count is greater than or equal to 1.5 × 109 / L, and the platelet count is greater than or equal to 100 × 109 / L;
• the total toxic value is less than or equal to one (except for cases of vomiting, alopecia or nausea).

When performing therapeutic procedures with the use of this therapeutic agent, it is necessary to regularly take a blood test. The frequency of this procedure is one time per week. The therapy should be stopped for a while or discontinued if there are the criteria described in list 1.

List №1.

Criteria for suspending or canceling drug use:

• with a level of toxicity AHN greater than or equal to 0.5 and lower than 1.5 × 109 / l;
• at toxicity values below the figure of 0.5 × 109 / L;
• with platelet counts that exceed or equal to 10, and below 100 × 109 / l;
• with platelet counts that are below the 10 × 109 / l mark;
• with CTC having a nonhematological form of toxicity of the 2nd, 3rd or 4th level (with the exception of such disorders as vomiting with alopecia and nausea).

Cycle No.1:

At the end of the 1st stage, after 1 month Temodal + RT the drug is prescribed for a period of 6 additional cycles of maintenance treatment. The sizes of portions in the 1st cycle are equal to 150 mg / m ², with daily intake for 5 days. Next, you need to suspend the therapy for 23 days.

Cycles number 2-6:

At the initial stage of the second cycle, it is allowed to increase the number of the active element to be used up to 200 mg / m ², provided that the level of non-hematological toxicity of the STS during the 1st cycle is below or equal to the 2 mark, the AFN level is higher or equal to the values of 1.5 × 109 / l, and the platelet counts are higher or equal to the figure of 100 × 109 / l.

A daily dosage of 200 mg / m ² is prescribed for use during the period of 5 days of each new cycle. At the same time, if the dosage size has not been increased in the 2nd cycle, in the subsequent it is also not necessary.

During the second stage of the course, the reduction in the drug use rate should be in accordance with the criteria listed in the lists 2, and 3.

When using Temodal 3 weeks after the use of the first portion of the drug, a complete blood test procedure is required.

List №2.

The parameters of temozolomide, required with supporting procedures:

• at a value of -1, the daily dosage amount of 100 mg / m ² should be reduced in advance;
• with a portion equal to zero, a daily dosage of 150 mg / m ² is the norm in the first cycle of therapy;
• at a dosage level of one, the portion size of 200 mg / m ² / day is the norm in the 2-6th cycles of therapy (if no toxicity exists).

List №3.

Criteria for reducing dosage or cancellation of drugs with supporting measures:

• if the level of toxicity of the ACCH is lower than 1x109 / l, it is required to reduce the TMZ by 1 level of the dose;
• if a reduction in portion is required, the drug should be stopped;
• when platelet counts are below 100 × 109 / l, drug use should be reduced by 1% in the TMZ;
• at CTC with non-hematologic form of toxicity (except for alopecia and vomiting with nausea), having the 3rd level, it is necessary to lower TMP to the 1st dosage level;
• with non-hematologic toxicity CTC (excluding complications such as vomiting, alopecia and nausea) with level 4, further administration of Temodal is prohibited.

[18], [19],

Use Temodal during pregnancy

Use Temodal during pregnancy or lactation - is prohibited.

Contraindications

The drug is contraindicated for persons with a strong intolerance with regard to its active element or other components. Intolerance is expressed in the form of allergy symptoms, including anaphylaxis, and in addition, in the form of urticaria.

Also, the drug is not prescribed to persons with high sensitivity relative to the dacarbazine element, since the metabolic process proceeds with the participation of the MTIC component.

Temodal can not be used in childhood.

[14]

Side effects Temodal

Use of the medication can cause the development of side-effects, the most frequent of which are constipation, headaches, vomiting with nausea, a feeling of weakness or fatigue, and also loss of appetite.

Vomiting with nausea can have a rather severe degree of severity, so to eliminate them, you may need to take medication. In addition, a decrease in the severity of some of these reactions can contribute to changes in the nutritional diet. If any of these complications persists or worsens, you should immediately consult your doctor.

More rarely, the use of drugs causes transient alopecia. To normal growth of hair, the situation usually returns after the end of therapy.

A single medicine also causes the development of such serious complications as swelling in the legs or ankles, ulcers on the oral mucosa, weak bleeding or bruising, and in addition to the difficulty of respiratory function. Also, Temodal can weaken the body's resistance to the effects of various infections.

Although temozolomide is used as a therapy for cancer, in isolated situations, the chance of developing another form of cancer (for example, cancer in the bone marrow) increases in some patients due to its administration.

If you notice swelling of the glands, hyperhidrosis, and sudden or unexplained weight loss when using the medication, you should immediately contact your doctor.

Strong manifestations of allergy to the drug develop only once, although their appearance is quite possible. Among the signs of itching, rashes, swelling (especially tongue with a throat and on the face), respiratory distress and severe dizziness.

[15], [16], [17]

Overdose

The effect of dosages of 0.5, 0.75, 1, and 1.25 g / m ²  (total dose for a 5-day cycle) was investigated in patients . The dosage of the toxicity limit was the hematologic toxicity observed with the use of any portion of the drug. Therefore, the higher the dose size of the drug used, the higher the hematological toxicity value.

Poisoning was noted when a patient had a dosage of 2 g / day. The duration of application was 5 days. In this case, the victim developed hyperthermia, pancytopenia and insufficiency of many internal organs, resulting in death.

There are data on people to whom Temodal was prescribed for use for more than 5 days (up to 2 months), resulting in the suppression of bone marrow function, and then death occurred.

[20], [21]

Interactions with other drugs

The combination with ranitidine does not affect the degree of absorption of the drug.

When combined with carbamazepine, dexamethasone, phenobarbital, phenytoin, and in addition to prochlorperazine, blockers of H2-terminus of histamine, and also ondansetron, there are no changes in the clearance rates of temozolamide.

The decrease in the clearance values of the active element of the drug occurs when combined with valproic acid. At the same time, the clearance rates decrease slightly.

Combination of Temodal with medications that contain elements that suppress bone marrow activity increases the risk of myelosuppression.

[22], [23], [24], [25]

Storage conditions

Temodal is required to contain in a place where moisture does not penetrate, with temperature values within 2-30 ° C.

Shelf life

Temodal is allowed to be used for 2 years from the date of manufacture of the therapeutic agent.

[26]

Analogues

Analogues of the drug are preparations of Temozolomide, Temozolomide-Rus and Temozolomide-Teva, and in addition Temomid and Temtital.

[27], [28], [29], [30]

Reviews

Temodal receives a large number of different reviews, most of which are marked by its high medicinal efficacy and the absence of negative reactions. Of the minuses, only the emergence of nausea and headaches - such side effects appear in every third person who uses this medicine.