Temodal

Temodal has antitumor properties.

Indications Temodala

It is used to eliminate the following pathologies:

• multiforme glioblastoma, which was diagnosed for the first time. In this case, the drug should be used in combination with radiation therapy procedures, and in addition with the need to perform supportive measures;
• malignant glioma - to eliminate relapses of this disease or if it progresses even in the case of standard treatment procedures;
• melanoma, which develops as a metastatic malignant neoplasm of a widespread nature. Temodal is used as the main drug.

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Release form

The drug is released in capsules of 5 and 20 mg, as well as 0.1, 0.14, 0.18 and 0.25 g - 5 capsules inside a blister, 4 blisters inside a box.

It is also produced in the form of a powder from which a solution is made – in 0.1 g vials.

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Pharmacodynamics

The active element of the drug that enters the bloodstream undergoes a process of rapid conversion of a non-enzymatic nature (at physiological pH values) – it is transformed into the active compound 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 at positions O6 and N7. These data allow us to conclude that the cytotoxic damage resulting from this process develops as an activator of the reductive activity of the methyl residue.

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Pharmacokinetics

Absorption.

Temozolomide is rapidly and almost completely absorbed, reaching the Cmax level after 1 hour (on average). Food reduces the degree and rate of absorption of the element. The average Cmax values in plasma are reduced by 32%, and the period of action of the active component is extended by two times (from 1 to 2.25 hours). A similar effect is observed when using the drug immediately after a hearty breakfast, which included fatty foods, also containing a large amount of carbohydrates.

Distribution processes.

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

Exchange processes.

Hydrolysis of the substance occurs spontaneously (if the pH is physiological), to form active species, MTIC, and the breakdown product - temozolomide acid. MTIC is then hydrolyzed to the element 5-amino-imidazole-4-carboxamide (APC), which is an intermediate component of the biosynthesis of nucleic acids with purine, as well as methylhydrazine. Elements of the hemoprotein P450 are not important participants in the metabolism of temozolomide and MTIC. Relative to the AUC of temozolomide, the effect of MTIC with APC is 2.4% and 23%, respectively.

Excretion.

Approximately 38% of the administered temozolomide from the total radioactive dose is excreted within the first week: 37.7% in the urine and another 0.8% in the feces.

The excretion period of the active substance from plasma is slightly less than 120 minutes. Most of the drug is excreted by the kidneys. After 24 hours of use, approximately 10% of temozolomide is excreted in the urine. This component can also be excreted as polar decay products that cannot be identified. Clearance values and half-life do not change depending on the portion size.

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Dosing and administration

The medication should be taken at a dosage of 75 mg/ ^m2 once a day for a period of 42 days, together with concomitant radiation therapy procedures (with a total dosage of 60 Gy, the number of fractions administered is 30 sessions).

The course of drug use should not be interrupted, although occasionally this action may be prescribed by the attending physician (if the patient has stable negative manifestations). If drug intake has been stopped, therapy should be resumed during the 42-day concomitant period, although it can be extended to 49 days if all the conditions described below are met:

• 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 in cases with vomiting, alopecia or nausea).

When carrying out treatment procedures using this therapeutic agent, it is necessary to regularly take a blood test. The frequency of this procedure is once a week. Therapy must be stopped for a while or discontinued if the criteria described in list No. 1 are present.

List #1.

Criteria for suspension or cancellation of medication:

• at the level of ACN toxicity exceeding or equal to 0.5 and lower than 1.5×109/l;
• at toxicity values below 0.5×109/l;
• with platelet counts that exceed or equal 10, as well as below 100×109/l;
• with platelet counts below 10×109/l;
• in CTC that has non-hematological toxicity of grade 2, 3 or 4 (excluding disorders such as vomiting with alopecia and nausea).

Cycle #1:

At the end of the 1st stage, after 1 month of Temodal+RT, the drug is prescribed for a period of 6 additional cycles of maintenance treatment. The dose sizes in the 1st cycle are 150 mg/m2 ^, with daily intake for 5 days. Then, the therapy should be suspended for 23 days.

Cycles #2-6:

At the initial stage of the 2nd cycle, it is allowed to increase the amount of the active element used to 200 mg/ ^m2, provided that the level of non-hematological toxicity of the CTC during the 1st cycle is below or equal to 2, the level of ANC is above or equal to 1.5×109/l, and the platelet count is above or equal to 100×109/l.

A daily dosage of 200 mg/ ^m2 is prescribed for use during the 5th day of each new cycle. In this case, if the dosage was not increased in the 2nd cycle, it is not necessary to do so in subsequent cycles.

During the 2nd stage of the course, the reduction in the rate of drug use should occur in accordance with the criteria specified in lists 2 and 3.

When using Temodal, 3 weeks after taking the first dose of the drug, a complete blood count must be performed.

List #2.

Temozolomide levels required for maintenance procedures:

• at dose values of -1, the daily dosage size of 100 mg/m2 ^should reduce the preliminary toxicity;
• with portion values equal to zero, a daily dosage of 150 mg/m2 ^is the norm in the 1st cycle of therapy;
• At a dosage level of one, a dose size of 200 mg/ ^m2 /day is normal in cycles 2–6 of therapy (if there is no toxicity).

List No. 3.

Criteria for reducing the dosage or discontinuing drugs during maintenance measures:

• if the ACN toxicity level is below 1x109/l, it is necessary to reduce the TMZ by 1 serving level;
• if a reduction in the portion is required, the medication should be stopped;
• if platelet counts are below 100×109/l, the use of the drug should be reduced by 1 dosage level;
• in case of CTC with non-hematological toxicity (except for alopecia and vomiting with nausea), which has the 3rd level, the TMZ should be reduced to the 1st dosage level;
• If non-hematological toxicity CTC (excluding complications such as vomiting, alopecia and nausea) is present with a level of 4, further use of Temodal is prohibited.

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Use Temodala during pregnancy

It is prohibited to use Temodal during pregnancy or lactation.

Contraindications

The drug is contraindicated for people with severe intolerance to its active ingredient 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 people with high sensitivity to the element dacarbazine, since the metabolic process occurs with the participation of the MTIC component.

Temodal should not be used in children.

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Side effects Temodala

The use of the drug may cause the development of side effects, the most common of which are constipation, headaches, vomiting with nausea, a feeling of weakness or fatigue, and also loss of appetite.

Vomiting and nausea can be quite severe, so medication may be needed to treat them. In addition, changes in diet may help alleviate some of these reactions. If any of these complications persist or worsen, you should consult your doctor immediately.

Less frequently, the use of drugs causes transient alopecia. The situation usually returns to normal hair growth after the end of therapy.

The drug alone also causes the development of such fairly serious complications as swelling in the legs or ankles, ulcers on the oral mucosa, slight bleeding or bruising, and in addition, difficulty breathing. Temodal can also weaken the body's resistance to the influence of various infections.

Although temozolomide is used as a treatment for cancer, in isolated situations, some patients may be at increased risk of developing another form of cancer (for example, cancer in the bone marrow) due to its use.

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

Severe manifestations of allergy to the drug develop only occasionally, although their occurrence is quite possible. Among the signs are itching, rashes, swelling (especially of the tongue with throat and on the face), respiratory disorders and severe dizziness.

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Overdose

The effect of doses of 0.5, 0.75, 1, and 1.25 g/m2 ⁽ total dose for a 5-day cycle) was studied in patients. The toxicity-limiting dose was hematological toxicity observed with any dose of the drug. Therefore, the higher the dose of the drug used, the higher the hematological toxicity values.

Poisoning was observed when the patient consumed a dosage of 2 g/day. The duration of use was 5 days. The victim developed hyperthermia, pancytopenia, and failure of multiple internal organs, resulting in death.

There are reports of people who were prescribed Temodal for more than 5 days (up to 2 months), which resulted in bone marrow suppression and then death.

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Interactions with other drugs

Combination with ranitidine does not affect the degree of absorption of the drug.

When combined with carbamazepine, dexamethasone, phenobarbital, phenytoin, as well as prochlorperazine, H2-histamine receptor blockers, and ondansetron, no changes in temozolomide clearance rates are observed.

The clearance values of the active element of the drug decrease when combined with valproic acid. In this case, the clearance values decrease slightly.

Combining Temodal with medications that contain elements that suppress bone marrow function increases the risk of developing myelosuppression.

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Storage conditions

Temodal should be kept in a place where moisture does not penetrate, at temperatures within the range of 2-30°C.

Shelf life

Temodal can be used for 2 years from the date of manufacture of the therapeutic agent.

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Analogues

The analogs of the drug are Temozolomide, Temozolomide-Rus and Temozolomide-Teva, as well as Temomid and Temcital.

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Reviews

Temodal receives a large number of different reviews, most of which note its high medicinal effectiveness and the absence of negative reactions. The only downsides are nausea and headaches - such side effects occur in every third person using this medicine.