Intaxel

Intaxel is an anticancer drug that has a plant based. It is produced by semi-art from berry yew.

The principle of the therapeutic effect of a drug is related to its ability to stimulate the activity of microtubule assembly located inside dimeric tubulin molecules. In addition, the medicinal substance helps stabilize the microtubule data structure and slow down the processes of dynamic reorganization during the development of the interphase, resulting in impaired mitotic cellular function.

[1], [2]

Indications Intaxel

It is used for such diseases:

• ovarian carcinoma : treatment of the 1st line in patients with common pathology or residual neoplasm (more than 1 cm) after performing a laparotomy (combined with cisplatin) and treatment of the 2nd line in case of metastasis after performing standard medical procedures that have not brought desired effect;
• breast carcinoma (presence of affected lymph nodes after the implementation of standard complex treatment (adjuvant therapy)); in case of recurrence of the disease, within half a year since the start of the adjuvant treatment - the 1st line procedure; carcinoma of the breast with metastases after not having the result of standard treatment - the event of the 2nd line;
• non-small cell lung carcinoma (first-line treatment in people who do not need surgery or radiation therapy (with cisplatin));
• angioendothelioma in persons with AIDS (treatment of the 2nd line, in case of failure of procedures using liposomal anthracyclines).

Release form

The release of the medication is implemented in the form of a concentrate for injection liquid, inside a bottle of 5 (30 mg), 17 (0.1 g), and 25 (0.15 g), 43.4 (0.26 g) or 50 ml ( 0.3 g); in a pack - 1 such bottle.

Pharmacodynamics

The drug leads to inhibition of hematopoietic processes within the bone marrow (severity depends on the size of the portion). The information obtained during the experimental studies showed that Intaxel has embryotoxic and mutagenic activity, and with it it leads to a weakening of reproductive activity.

[3], [4], [5]

Pharmacokinetics

After intravenous 3-hour infusion of 135 mg / m ² servings, the Cmax level of the drug is 2170 ng / ml, and the AUC is 7952 ng / hour / ml; if the above dosage is administered over a 24-hour period, the values are, respectively, 195 ng / ml, as well as 6300 ng / h / ml. The values of Cmax and AUC depend on the size of the portion: in the case of a 3-hour procedure, increasing the dosage to 175 mg / m ² causes an increase in these values by 68%, as well as 89%; in the case of a 24-hour procedure - by 87%, as well as 26%.

Intlasma synthesis with proteins is 88-98%. The term half-life of the blood inside the tissue is half an hour. The substance passes without complications and is absorbed into the tissue - mainly pancreas, spleen, heart, intestines with stomach, liver and muscles.

The metabolic processes are carried out inside the liver through hydroxylation using hemoprotein P450 CYP2D8 isoenzymes (this forms the metabolic component of 6-α-hydroxypaclitaxel), as well as CYP3CA4 (with the formation of metabolic elements of 3-para-hydroxypaclitaxel, as well as 6-α, 3-para- 2-hydroxypaclitaxel). Excretion is mainly realized with bile - by 90%. In the case of repeated infusions, the drug does not accumulate.

The term half-life and systemic clearance may vary depending on the dosage and duration of the intravenous procedure: 13.1-52.7 hours, respectively, as well as 12.2-23.8 l / h / m ². When using intravenous infusions (duration of 1-24 hours), systemic renal excretion equals 1.3-12.6% of the portion size (in the range of 15-275 mg / m ² ), from which it can be concluded that there is a pronounced extrarenal clearance.

[6], [7]

Dosing and administration

To prevent severe manifestations of intolerance, each patient should be premedicated using antihistamine drugs, GCS, as well as antagonists of the endings of histamine H2. For example, you need to take orally 20 mg of the substance dexamethasone (or equivalent of this component) about 12 and 6 hours before using Intaxel. Intravenous administration of 50 mg of diphenhydramine (or equivalent) can also be performed using 0.3 g of cimetidine or 50 mg of ranitidine by intravenous injection of 0.5-1 hour before using the drug.

During the personal selection of dosages and treatment regime should take into account the information provided by the special literature.

The drug should be administered intravenously - after a 3-hour or 24-hour infusion per serving, respectively, 175 or 135 mg / m ²; the gap between these procedures should be 21 days. The drug is used both as monotherapy, and in combination with cisplatin (for non-small cell lung carcinoma and ovarian carcinoma) or with doxorubicin (breast carcinoma).

In the case of angioendothelioma in people with AIDS, a 3-hour infusion of 0.1 mg / m ^{2 of the} drug is required at 14-day intervals.

Drug use cannot be repeated until the neutrophil count is at least 1500 / μl, and the platelet values are at least 100 000 / μl. People whose drug use causes severe neutropenia (neutrophil level is <500 / µl for the first week or longer) or severe polyneuropathy, in the future you need to reduce its portion by 20%.

Medical infusion fluid must be made before its use. The concentrate is dissolved in 0.9% NaCl or 5% dextrose liquid; 5% dextrose in 0.9% injectable NaCl or Ringer's solution may also be used. The final concentration of the drug should be in the range of 0.3-1.2 mg / ml. Prepared substances are capable of opalescence, because they contain a carrier base. It should be noted that the opalescence of the drug persists after the filtration procedure.

The drug is applied using a system that has a built-in special membrane-type filter (its pore size is a maximum of 0.22 micron).

[10]

Use Intaxel during pregnancy

The drug should not be prescribed in case of pregnancy or breastfeeding.

Contraindications

The main contraindications:

• severe intolerance associated with paclitaxel or other elements of the drug (especially with respect to polyoxyl castor oil);
• neutropenia developed before the start of therapy (the number of neutrophils equals <1.5'10 9 / l; for angioendothelioma in persons with AIDS, the neutrophil index is <1.0'10 9 / l);
• having severe severity of infection with angioendothelioma, which cannot be controlled.

[8]

Side effects Intaxel

The intensity and frequency of development of adverse symptoms depend on the size of the dosage:

• hematopoietic dysfunction: anemia, neutro - or thrombocytopenia. Inhibition of hematopoietic activity (mainly granulocyte sprout) is the main toxic property, because of which it is necessary to limit the amount of drugs. The maximum decrease in neutrophil counts often occurs by the 8-11th day, and their stabilization occurs by the 22nd day;
• symptoms of intolerance: during the first few hours after using the drug, there may be signs of hypersensitivity, including blood tides to the face, a decrease in blood pressure, an epidermal rash, bronchial spasm, pain in the sternum area, angioedema and urticaria, which has a generalized nature. There are few pains in the back and chills;
• disorders of the work of the cardiovascular system: tachycardia or bradycardia, a decrease or increase (less often) of blood pressure values, AV blockade, a change in ECG readings, cardiac rhythm disorder, ventricular bigemia and venous vessels thrombosis;
• problems with respiratory function: pulmonary fibrosis, an interstitial type of pneumonia affecting pulmonary arteries, and in addition to an increase in the occurrence of radiation-induced pneumonitis in individuals who are simultaneously undergoing radiation therapy sessions;
• lesions affecting NA: polyneuropathy (mainly paresthesia); rarely there is encephalopathy, seizures (grand mal varieties), problems with the optic nerve, and in addition ataxy and neuropathy of a vegetative nature, in which orthostatic collapse and paralytic intestinal blockage develop;
• disorders associated with the structure of muscles and bones: myalgia or arthralgia;
• problems with the work of the digestive tract: diarrhea, anorexia, nausea, constipation, mucositis and vomiting; single obstruction of the intestine in the active phase, intestinal perforation, colitis of the ischemic variety and thrombosis affecting the mesenteric artery; increased activity of intrahepatic transaminases (mainly ACT), serum bilirubin and alkaline phosphatase. There is information about the appearance of liver encephalopathy and hepatonecrosis;
• lesions of the epidermis: alopecia; occasionally discolouration of the nail bed or a pigmentation disorder;
• disorders associated with the senses: there is conjunctivitis, a weakening of visual acuity and increased watery eyes;
• local signs: edema, thrombophlebitis with erythema, pain, pigmentation with induction of the epidermis in the injection area; during extravasation, necrosis and inflammation may develop, affecting the subcutaneous layer;
• others: systemic malaise along with asthenia, and in addition, a decrease in tolerance for infections (of any origin).

[9]

Overdose

Intoxication can develop quite severe negative symptoms, including suppression of bone marrow activity, neurotoxic effects of a peripheral nature and inflammation that affects the mucous membranes.

Paclitaxel does not have an antidote. Symptomatic treatment procedures are carried out.

[11]

Interactions with other drugs

Cisplatin reduces the systemic clearance of paclitaxel by approximately 20% (more intense myelosuppression is observed when the drug is administered after using cisplatin).

Combining Intaxel with ranitidine or diphenhydramine, and in addition with cimetidine or dexamethasone, does not change the indices of paclitaxel synthesis with intraplasma protein.

Substances that slow down the oxidation of microsomes (among them diazepam with ketoconazole, quinidine with cimetidine, cyclosporine, and verapamil) inhibit the exchange of paclitaxel.

Castor oil (polyoxyethylated) oil in the composition of the drug can lead to the extraction of DEHP from PVC packaging; however, the indicators washout DEHP increased in accordance with the increase in the performance of the solution and the duration of therapy.

[12], [13]

Storage conditions

Intaxel should be kept in a dark and closed place from small children. The temperature level is not more than 25 ° С. It is forbidden to freeze the drug.

[14]

Shelf life

Intaxel can be used throughout the 2-year term from the moment of manufacture of the drug.

[15], [16], [17]

Application for children

There is no information regarding the effectiveness of the action and the safety of Intacel when it is administered in pediatrics.

[18], [19]

Analogs

Analogues of the medication are the substances Taxol, Paclitaxel, Betaxolol with Abitaxel, Mitotax, Cindaxel and Paclitax with Paxen.

[20]