Temozolomide

Temozolomide has an immunosuppressive and antitumor effect.

Indications Temozolomide

It is used in the treatment of malignant gliomas, and in addition, with the development of relapses or the progression of the disease after the patient has passed a standard treatment course.

Also prescribed for therapy with malignant melanoma, which has a common form, and against which metastases developed (as a medicament of the main series).

[1], [2], [3]

Release form

Release of the medication is carried out in capsules having a volume of 5, 20, and also 100 or 140 and 250 mg, inside the vials (in the amount of 5 or 20 pieces).

[4], [5]

Pharmacodynamics

Temozolomide is a drug with alkylating properties, which has an antitumor effect. Structure of the drug - imidazotetrasin.

Inside the circulatory system (at physiological pH), a rapid chemical transformation of the substance is performed, at which the active component of the MTIC is formed. According to some reports, the cytotoxicity of this component is mainly due to the processes of alkylation of guanine (at the position of type O6), as well as an additional alkylation process (at the position of type N7). It is likely that the resulting cytotoxic damage activates the mechanism in which aberrant reduction of the residual methyl takes place.

[6], [7], [8]

Pharmacokinetics

When administered orally, the drug is absorbed at high speed from the digestive tract. The plasma Cmax level is observed on average after 30-90 minutes (under any conditions it should be at least 20 minutes) after using a single dose of temozolomide. In the case of eating with food, a decrease of 33% in Cmax and a 9% in AUC was recorded.

The medicinal substance passes through the BBB at high speed and enters the CSF. Synthesis with intracellular protein is 10-20%.

The half-life of the substance from the plasma is about 1.8 hours. Excretion occurs at high speed (mainly through the kidneys).

At the end of 24 hours after oral administration, approximately 5-10% of the dosage is found in the urine (unchanged substance). The residue is excreted in the form of hydrochloride 4-amino-5-imidazole-carboxamide or undetermined polar decomposition products.

[9], [10], [11], [12], [13], [14], [15]

Dosing and administration

Capsules should be swallowed whole, washed down with water. Do this on an empty stomach, 60 minutes before eating.

The size of the initial portion for an adult is 0.2 g / m ², once a day for 5 consecutive days in a 4-week treatment cycle.

Persons who had previously undergone chemotherapy procedures are required to reduce the size of the initial dosage to 0.15 g / m ². Further, it is increased to a standard 0.2 g / m ² in the 2nd cycle.

The duration of the therapeutic cycle is selected individually.

[22], [23], [24], [25], [26], [27],

Use Temozolomide during pregnancy

Medication can not be used by pregnant women or lactating women.

Women and men who are in reproductive age should use reliable contraceptives for at least half a year after completion of therapy with Temozolomide.

Contraindications

The main contraindications:

• the presence of hypersensitivity to the drug;
• Myelosuppression in severe degree.

Caution during the use of drugs is necessary if the patient has problems with the liver or kidneys, as well as people over the age of 70 and those who need to maintain a high concentration of attention at work.

[16], [17]

Side effects Temozolomide

Taking a medication can trigger the appearance of certain side-effects:

• disorders affecting the digestive function: vomiting, anorexia, nausea and abdominal pain, and in addition diarrhea and constipation, flavors and signs of dyspepsia;
• problems with the CNS: headaches, paresthesia, fatigue or drowsiness and dizziness;
• dermatological signs: alopecia, skin rash or itching;
• disorders of respiratory activity: the appearance of dyspnea;
• disorders of hematopoiesis: anemia, leuko- or pancytopenia, as well as thrombocytopenia or neutropenia of the 3rd or 4th degree of severity;
• others: asthenia, chills, fever, a feeling of malaise and weight loss.

[18], [19], [20], [21]

Overdose

Among the signs of intoxication is the development of neutropenia. Thrombocytopenia may also occur - in the case of drug administration in single portions of 1 g / m ².

[28], [29], [30]

Interactions with other drugs

When combining the drug with valproic acid, the values of clearance of Temozolomide decrease.

The combination of the drug with other drugs that suppress bone marrow activity increases the likelihood of myelosuppression.

[31], [32], [33], [34]

Storage conditions

Temozolomide is required to be kept at temperature values of not more than 25 ° C.

Shelf life

Temozolomide is allowed to be used for 36 months from the date of manufacture of the therapeutic agent.

[35],

Application for children

There are no data on the use of drugs in children younger than 3 years of age who are ill with polyglobal glioblastoma, and also in persons under 18 years of age with melanoma of a malignant nature. Also, there is only limited information regarding the use of a medicament for glioma in persons under the age of 3 years.

[36], [37], [38], [39]

Analogues

Analogues of the medication are Tezal, Temomide with Temodal, and in addition Temozolomid-Teva, Temozolomide-Rus, Temozolomide-TL and Temtital.

[40], [41], [42], [43], [44], [45]

Reviews

Temozolomide demonstrates high efficiency in the treatment of anaplastic form of astrocytoma. In addition, he is appointed during the radiotherapy procedures, as well as at the end. The drug is also used for the therapy of the newly discovered polyglobal glioblastoma. Today, the main treatment for people with glioblastoma is a combination of Temozolomide and radiotherapy procedures.

Judging by the reviews, side manifestations of drugs are easy enough, because the cumulative toxicity of the drug is rather low. But still it is advisable to apply it only if there are registered predicted factors of drug effectiveness (the most weight is the level of methylation of the MGMT element).