Intaxel

Intaxel is a plant-based anti-tumor drug produced semi-artificially from the yew tree.

The principle of the drug's therapeutic effect is related to its ability to stimulate the activity of microtubule assembly located inside dimeric tubulin molecules. In addition, the drug helps to stabilize the structure of these microtubules and slow down the processes of dynamic reorganization during the development of the interphase, as a result of which mitotic cellular function is disrupted.

[ 1 ], [ 2 ]

Indications Intaxela

It is used for the following diseases:

• ovarian carcinoma: first-line treatment in individuals with widespread pathology or residual neoplasm (over 1 cm) after laparotomy (in combination with cisplatin) and second-line treatment in case of metastases after standard treatment procedures that did not bring the desired effect;
• breast carcinoma (presence of affected lymph nodes after standard complex treatment (adjuvant therapy)); in case of relapse of the disease, within six months from the start of adjuvant treatment - 1st line procedures; breast carcinoma with metastases after standard treatment that has failed - 2nd line measures;
• non-small cell lung carcinoma (first-line treatment in people who do not require surgery or radiation therapy (with cisplatin));
• angioendothelioma in people with AIDS (second-line treatment, in case of ineffectiveness of procedures using liposomal anthracyclines).

Release form

The drug is released in the form of a concentrate for injection liquid, inside vials of 5 (30 mg), 17 (0.1 g), as well as 25 (0.15 g), 43.4 (0.26 g) or 50 ml (0.3 g); in a pack - 1 such vial.

Pharmacodynamics

The drug leads to suppression of hematopoietic processes in the bone marrow (the severity depends on the portion size). Information obtained during experimental studies showed that Intaxel has embryotoxic and mutagenic activity, and at the same time it leads to weakening of reproductive activity.

[ 3 ], [ 4 ], [ 5 ]

Pharmacokinetics

After intravenous 3-hour infusion of a 135 mg/ ^m2 portion, the Cmax level of the drug is 2170 ng/mL, and the AUC value is 7952 ng/hour/mL; if the above-mentioned dosage is administered over 24 hours, the values are 195 ng/mL and 6300 ng/hour/mL, respectively. The Cmax and AUC values depend on the portion size: in the case of a 3-hour procedure, an increase in the dosage to 175 mg/m2 causes ^an increase in these values by 68% and 89%; in the case of a 24-hour procedure - by 87% and 26%.

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

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

The half-life and systemic clearance may vary depending on the dosage and duration of the intravenous procedure: 13.1-52.7 hours and 12.2-23.8 L/hour/m2 ^, respectively. When using intravenous infusions (duration 1-24 hours), systemic renal excretion is equal to 1.3-12.6% of the portion size (in the range of 15-275 mg/m2 ⁾, from which one can conclude about the pronounced extrarenal clearance.

[ 6 ], [ 7 ]

Dosing and administration

To prevent severe manifestations of intolerance, each patient should be premedicated with antihistamines, GCS, and histamine H2 antagonists. For example, 20 mg of dexamethasone (or equivalent) should be taken orally approximately 12 and 6 hours before using Intaxel. Intravenous administration of 50 mg of diphenhydramine (or equivalent) may also be performed, using 0.3 g of cimetidine or an intravenous injection of 50 mg of ranitidine 0.5-1 hour before using the drug.

When selecting individual dosages and treatment regimens, it is necessary to take into account the information provided in specialized literature.

The drug should be administered intravenously - via a 3-hour or 24-hour infusion in a dose of 175 or 135 mg/m2 ^, respectively; the interval between these procedures should be 21 days. The drug is used as monotherapy or in combination with cisplatin (for non-small cell lung carcinoma and ovarian carcinoma) or doxorubicin (breast carcinoma).

^{In the case of angioendothelioma in people with AIDS, a 3-hour infusion of 0.1 mg/ m2} of the drug is required at 14-day intervals.

The drug should not be used again until the neutrophil count is at least 1500/μl and the platelet count is at least 100,000/μl. People who develop severe neutropenia (neutrophil count <500/μl for 1 week or longer) or severe polyneuropathy while using the drug should have their dose reduced by 20%.

The infusion medicinal fluid must be prepared before use. The concentrate is dissolved in 0.9% NaCl or 5% dextrose fluid; 5% dextrose in 0.9% injection NaCl or Ringer's solution can also be used. The final concentration of the drug should be in the range of 0.3-1.2 mg/ml. The finished substances are capable of opalescence, because they contain a carrier base. It should be noted that the opalescence of the drug is preserved after the filtration procedure.

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

[ 10 ]

Use Intaxela during pregnancy

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

Contraindications

Main contraindications:

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

[ 8 ]

Side effects Intaxela

The intensity and frequency of development of side effects depend on the dosage size:

• disorders of hematopoietic function: anemia, neutro- or thrombocytopenia. Suppression of hematopoietic activity (mainly granulocyte sprout) is the main toxic property, due to which it is necessary to limit the dose of drugs. The maximum decrease in neutrophils often occurs by the 8th-11th day, and their stabilization occurs by the 22nd day;
• intolerance symptoms: during the first few hours after taking the medicine, signs of hypersensitivity may be observed, including flushing of the face, decreased blood pressure, epidermal rash, bronchial spasm, chest pain, Quincke's edema and generalized urticaria. Back pain and chills are occasionally observed;
• disorders of the cardiovascular system: tachycardia or bradycardia, decrease or increase (less often) in blood pressure, AV block, changes in ECG readings, heart rhythm disorders, ventricular bigeminy and thrombosis affecting the venous vessels;
• problems with respiratory function: pulmonary fibrosis, interstitial pneumonia, embolism affecting the pulmonary arteries, and in addition, an increased incidence of radiation pneumonitis in people who are simultaneously undergoing radiation therapy sessions;
• lesions affecting the nervous system: polyneuropathy (mainly paresthesia); occasionally, encephalopathy, seizures (varieties of grand mal), problems with the optic nerve, and in addition, ataxia and neuropathy of a vegetative nature, in which orthostatic collapse and paralytic intestinal obstruction develop;
• disorders associated with the structure of muscles and bones: myalgia or arthralgia;
• problems with the digestive tract: diarrhea, anorexia, nausea, constipation, mucositis and vomiting; isolated cases of active intestinal obstruction, intestinal perforation, ischemic colitis and thrombosis affecting the mesenteric artery; increased activity of intrahepatic transaminases (mainly AST), serum bilirubin and alkaline phosphatase. There is information about the occurrence of liver encephalopathy and hepatonecrosis;
• epidermal lesions: alopecia; occasionally, discoloration of the nail bed or pigmentation disorder occurs;
• disorders associated with the sensory organs: conjunctivitis, decreased visual acuity and increased lacrimation are observed;
• local signs: swelling, thrombophlebitis with erythema, pain, pigmentation with induration of the epidermis in the injection area; with extravasation, necrosis and inflammation may develop, affecting the subcutaneous layer;
• others: systemic malaise together with asthenia, and in addition, a weakening of tolerance to infections (of any origin).

[ 9 ]

Overdose

Intoxication can cause quite severe negative symptoms, including suppression of bone marrow activity, peripheral neurotoxic effects, and inflammation affecting the mucous membranes.

Paclitaxel has no antidote. Symptomatic treatment procedures are used.

[ 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 the use of cisplatin).

Combination of Intaxel with ranitidine or diphenhydramine, as well as with cimetidine or dexamethasone does not change the rates of paclitaxel synthesis with intraplasmic protein.

Substances that slow down the oxidation of microsomes (including diazepam with ketoconazole, quinidine with cimetidine, cyclosporine, and verapamil) inhibit the processes of paclitaxel metabolism.

The castor oil (polyoxyethylated) contained in the medicinal product may lead to the extraction of DEHP from the PVC packaging; in this case, the DEHP leaching rates increase in accordance with the increase in the solution rates and the duration of therapy.

[ 12 ], [ 13 ]

Storage conditions

Intaxel should be stored in a dark place, out of the reach of small children. The temperature level should not exceed 25°C. It is prohibited to freeze the medicine.

[ 14 ]

Shelf life

Intaxel can be used for a 2-year period from the date of drug production.

[ 15 ], [ 16 ], [ 17 ]

Application for children

There is no information regarding the efficacy and safety of Intaxel when administered in pediatrics.

[ 18 ], [ 19 ]

Analogues

The analogs of the drug are Taxol, Paclitaxel, Betaxolol with Abitaxel, Mitotax, Sindaxel and Paclitax with Paxen.

[ 20 ]