Paclitaxel-jen

One of the representatives of antineoplastic and immunomodulating drugs based on paclitaxel is Paclitaxel-jen - an injection solution manufactured by the Indian pharmaceutical corporation "Genom Biotech pvt. Ltd.

[1], [2], [3]

Indications Paclitaxel-jen

The anti-neoplastic preparation Paclitaxel-jen is used as a part of chemotherapy for cancer processes in the ovaries, in the mammary glands, with non-small cell lung cancer in Kaposi's sarcoma in HIV-infected patients.

[4], [5], [6], [7]

Release form

The antineoplastic agent Paclitaxel-jen is made in the form of an injection solution for intravenous infusions.

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

Among the additional ingredients, there is a certain amount of citric acid, ricin oil, alcoholic denatured alcohol.

[8], [9],

Pharmacodynamics

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

Paclitaxel-jen is involved in the induction of the formation of abnormal microtube gathers throughout the cell cycle, and also provokes the formation of multiple "radiant" microtubes in the mitotic period, which causes a halt in the life cycle in the G² phase or M phase.

As a result of the effects of Paclitaxel-jen, the formation of the spindle of mitosis is triggered. The tumor cell ceases to divide, the skeleton of the cell and its mobility, the processes of intracellular motion and the transmembral transfer of impulses are broken, which together leads to the death of the cancer cell.

[10], [11], [12], [13]

Pharmacokinetics

Kinetic features of paclitaxel-jen were investigated with a three-hour intravenous infusion of a solution in an amount of 135-175 mg per m².

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

 Increasing the dosage by 30% leads to an increase in the limiting concentration and AUC by 75% and 81%, respectively.

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

The connection with plasma proteins can range from 89 to 98%.

Premedication with cimetidine, ranitidine, dexamethasone, diphenhydramine has no effect on the association of the active ingredient with proteins.

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

Removal of the drug occurs through bile.

[14], [15], [16], [17], [18]

Dosing and administration

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

The usual dosage of Paclitaxel-jen is 175 mg per m²: a 3-hour infusion once every three weeks (if the platelet count in the bloodstream is equal to or above 100,000, and the absolute neutrophil count is equal to or above 1500 per mm3, in other situations, measures postpone until recovery of blood counts). If at the initial stage of treatment the patient experiences severe neutropenia (absolute neutrophil count below 500 per mm3) for a week or more, or neutropenia occurs against the background of infections, the dosage of Paclitaxel-jen is reduced by 20%.

Prior to the treatment of Paclitaxel-jen, patients are prescribed premedication, which includes the use of:

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

The infusion of Paclitaxel-jen is carried out using a membrane filter integrated in the infusion system with cells no wider than 0.22 μm. The system should not use parts made of polyvinyl chloride.

[26], [27], [28]

Use Paclitaxel-jen during pregnancy

Treatment of paclitaxel-jen and periods of pregnancy and breastfeeding are incompatible.

Contraindications

Not prescribed treatment Paclitaxel-jen:

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

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

Side effects Paclitaxel-jen

Infusion solution Paclitaxel-jen in a standard dosage and with a competent infusion usually does not cause side effects. Toxic effect can be manifested by oppression of the hematopoietic function. Neutrophilia is found around 8-11 days, and on day 22 the neutrophil count is normalized. Significant neutropenia is found in 27% of patients: it is short-lived and does not lead to the appearance of infectious complications. Only in 1% of cases the duration of a significant degree of neutropenia of the fourth degree is more than one week.

The emergence of complex cases of thrombocytopenia and anemia is found in patients with low hematopoietic reserves (with multiple bone metastases, frequent chemotherapeutic courses).

To prevent the development of hematopoietic complications during the treatment period, Paclitaxel-jen should observe weekly changes in blood counts, and in the presence of indications, lower the infusion amount of the drug.

In order to prevent hypersensitive reactions, premedication is always performed first. This allows to reduce to 3% the severity of such reactions.

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

In 3% of patients, bradycardia may occur, and a 22% drop in blood pressure. Such cases are not an excuse for additional treatment or stopping the infusion.

To prevent possible disorders, an electrocardiogram must be prescribed prior to infusion and throughout the chemotherapy course.

Paclitaxel-jen is neurotoxic and can provoke the development of transient peripheral sensory neuropathies.

In 60% of patients there are pains in the muscles and joints.

Alopecia is typical of almost all patients undergoing treatment with Paclitaxel-jen.

In addition, during the chemotherapy of Paclitaxel-jen, indications of dyspepsia, stomatitis, changes in hepatic transaminase activity and an increase in the amount of bilirubin may occur.

[22], [23], [24], [25]

Overdose

The signs of overdose are:

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

Diagnosis can be found: oppression of bone marrow function, mucositis, peripheral neuropathy.

When an overdose is prescribed symptomatic treatment, since there is no special medication with the properties of the antidote.

[29], [30], [31],

Interactions with other drugs

The combination of paclitaxel-jen with cisplatin leads to more significant myelosuppression.

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

The content of doxorubicin in the blood serum can increase with the introduction of paclitaxel first, and then - doxorubicin.

Preparations of testosterone, quercetin, ethinyl estradiol, retinoic acid inhibit the formation of hydroxypaclitaxel "in vitro". As a result of combination with such drugs as substrates, inhibitors and inducers of CYP 2C8 and CYP 3A4, the kinetic properties of paclitaxel-jen "in vivo" may vary.

[32], [33], [34]

Storage conditions

Paclitaxel-jen is stored in a refrigerator, providing constant temperature values of + 2 ° C to + 8 ° C. The storage location must be darkened and not accessible to children.

[35], [36], [37]

Shelf life

Packages are stored with Paclitaxel-jen up to 2 years.

[38], [39], [40], [41], [42]