Paclitaxel-gen

One of the representatives of antineoplastic and immunomodulatory drugs based on paclitaxel is Paclitaxel-gene - an injection solution produced by the Indian pharmaceutical corporation Genom Biotech pvt. Ltd.

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Indications Paclitaxel-gen

The antineoplastic drug Paclitaxel-gen is used as part of chemotherapy for cancer processes in the ovaries, mammary glands, non-small cell lung cancer, and Kaposi's sarcoma in HIV-infected patients.

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Release form

The antineoplastic drug Paclitaxel-gen is produced as an injection solution for intravenous infusion.

The drug is represented by the active ingredient paclitaxel, the content of which in 1 ml is 6 mg.

Additional ingredients include some citric acid, castor oil, and denatured alcohol.

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Pharmacodynamics

The drug is considered a typical representative of antimitotic cytostatic antitumor drugs. Its principle of therapeutic action is related to interference in the process of cell division. Paclitaxel-gene antivises the collection of microtubes from tubulin dimers, normalizes current processes and inhibits depolymerization, upsetting the balance of dimers and polymers on the side of the latter.

Paclitaxel-gen is involved in the induction of abnormal microtubule assembly formation throughout the cell cycle and also induces the formation of multiple "radial" microtubules during the mitotic period, which causes the cell cycle to arrest in the G² or M phase.

As a result of the action of Paclitaxel-gen, the formation of the mitotic spindle is launched. The tumor cell stops dividing, the cell skeleton and its mobility are disrupted, the processes of intracellular movement and transmembral transmission of impulses, which together leads to the death of the cancer cell.

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Pharmacokinetics

The kinetic properties of Paclitaxel-gen were studied using a three-hour intravenous infusion of a solution in an amount of 135-175 mg/m².

The average distribution volume was 198-688 liters per m². The content of the active ingredient in the bloodstream decreases according to a two-phase curve. Increasing the dosage leads to the development of a non-linear dependence.

An increase in dosage by 30% results in an increase in maximum concentration and AUC by 75% and 81%, respectively.

Repeated multiple infusions do not cause accumulation of the active ingredient.

Plasma protein binding can range from 89 to 98%.

Premedication with cimetidine, ranitidine, dexamethasone, diphenhydramine does not affect the binding of the active ingredient to proteins.

Metabolic processes have not been sufficiently studied, but it is known that biological transformation reactions occur in the liver with the formation of hydroxyline end products. The half-life of the active substance occurs within 3-52.7 hours, with an average clearance rate of 11.6-24 l per hour per m².

The drug is excreted through bile.

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Dosing and administration

Before infusion, Paclitaxel-gen solution is diluted in 5% glucose or saline, containing 0.3-1.2 mg of paclitaxel in 1 ml.

The usual dosage of Paclitaxel-gen is 175 mg/m²: 3-hour infusion once every three weeks (if the platelet count in the bloodstream is 100,000 or higher and the absolute neutrophil count is 1,500/mm³ or higher; in other situations, treatment is postponed until blood counts are restored). If at the initial stage of treatment the patient develops severe neutropenia (absolute neutrophil count below 500/mm³) for a week or more, or neutropenia occurs against the background of infections, the dosage of Paclitaxel-gen is reduced by 20%.

Before starting treatment with Paclitaxel-gen, patients are prescribed premedication, which includes the use of:

• glucocorticosteroid hormones (eg, 20 mg dexamethasone intramuscularly or orally 12 hours and 6 hours before paclitaxel infusion);
• antihistamines (for example, 50 mg diphenhydramine intravenously by jet stream half an hour before the infusion of paclitaxel);
• h2-histamine receptor blocking drugs (eg, 300 mg cimetidine or 50 mg ranitidine intravenously half an hour before paclitaxel infusion).

Infusion of Paclitaxel-gene is carried out using a membrane filter with cells no wider than 0.22 µm built into the infusion system. The system should not contain any parts made of polyvinyl chloride.

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Use Paclitaxel-gen during pregnancy

Treatment with Paclitaxel-gen and periods of pregnancy and breastfeeding are incompatible.

Contraindications

Treatment with Paclitaxel-gen is not prescribed:

• if you have a tendency to hypersensitivity to the drug;
• with significant neutropenia (below 1500/1 mm³);
• pregnant and lactating patients.

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Side effects Paclitaxel-gen

Infusion solution Paclitaxel-gen in standard dosage and with proper infusion usually does not cause side effects. Toxic effect can be manifested by suppression of hematopoietic function. Neutrophilia is detected approximately by 8-11 days, and on the 22nd day the number of neutrophils is normalized. Significant neutropenia is detected in 27% of patients: it is short-term and does not lead to infectious complications. Only in 1% of cases the duration of significant neutropenia of the fourth degree is more than one week.

The occurrence of complex cases of thrombocytopenia and anemia is detected in patients with reduced hematopoietic reserves (with multiple bone metastases, frequent chemotherapy courses).

To prevent the development of hematopoietic complications during treatment with Paclitaxel-gen, changes in blood counts should be monitored weekly and, if indicated, the infused amount of the drug should be reduced.

To prevent hypersensitivity reactions, premedication is always administered first. This allows the severity of such reactions to be reduced to 3%.

Initial signs of hypersensitivity in the form of shortness of breath, hypertension, chest pain occur at the very beginning of the infusion (in the third to tenth minute). If measures to prevent allergies are taken in a timely manner, there is no need to stop the infusion.

Bradycardia may occur in 3% of patients, and a decrease in blood pressure may occur in 22%. Such cases are not a reason for additional treatment or stopping the infusion.

To prevent possible disorders, an electrocardiogram is mandatory before the infusion and throughout the entire chemotherapy course.

Paclitaxel-gen is neurotoxic and may cause transient peripheral sensory neuropathies.

60% of patients experience muscle and joint pain.

Hair loss is common in almost all patients undergoing treatment with Paclitaxel-gen.

In addition, during chemotherapy with Paclitaxel-gen, signs of dyspepsia, stomatitis, changes in the activity of liver transaminases and an increase in the amount of bilirubin may occur.

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Overdose

Signs of overdose are:

• the appearance of edema;
• painful sensations;
• redness at the injection site;
• state of weakness;
• dyspepsia;
• drop in blood pressure;
• slowing of heart rate;
• skin rash;
• sensation of local itching.

Diagnostic findings may include: suppression of bone marrow function, mucositis, and peripheral neuropathy.

In case of overdose, symptomatic treatment is prescribed, since there is no special medication with antidote properties.

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Interactions with other drugs

The combination of Paclitaxel-gen with cisplatin results in more significant myelosuppression.

The use of ketoconazole can inhibit the metabolic reactions of paclitaxel.

Serum doxorubicin levels may increase when paclitaxel is administered first followed by doxorubicin.

Testosterone, quercetin, ethinyl estradiol, and retinoic acid preparations inhibit the formation of hydroxypaclitaxel "in vitro". As a result of combination with such preparations as substrates, inhibitors, and inducers of CYP 2C8 and CYP 3A4, the kinetic properties of Paclitaxel-gene "in vivo" may change.

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Storage conditions

Paclitaxel-gene is stored in a refrigerator, providing constant temperature indicators of +2°C - +8°C. The storage place should be dark and inaccessible to children.

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Shelf life

Packages with Paclitaxel-gen are stored for up to 2 years.

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