Paclitaxel-LNS 6 mg/ml 23.3ml

Paclitaxel-LNS® (paclitaxel) is an antitumor drug of natural origin obtained semi-synthetically from the plant Taxus Baccata.

Indications

– Ovarian cancer (first-line therapy of patients with advanced disease or residual tumor (more than 1 cm) after laparotomy (in combination with cisplatin) and second-line therapy for metastases after standard therapy with no positive result).

– Breast cancer (presence of affected lymph nodes after standard combination therapy (adjuvant treatment); after disease relapse, within 6 months after initiation of adjuvant therapy – first-line therapy; metastatic breast cancer after ineffective standard therapy – second-line therapy).

– Non-small cell lung cancer (first-line therapy for patients who are not scheduled for surgical treatment and/or radiation therapy (in combination with cisplatin).

– Kaposi’s sarcoma in AIDS patients (second-line therapy, after ineffective therapy with liposomal anthracyclines).

Active ingredient

How to take, the dosage

In order to prevent severe hypersensitivity reactions, all patients should be premedicated with glucocorticosteroids, antihistamines and H2-histamine receptor antagonists. For example, 20 mg of dexamethasone (or equivalent) orally approximately 12 and 6 hours before administration of Paclitaxel-LENS®, 50 mg of diphenhydramine (or equivalent) intravenously, and 300 mg of cimetidine or 50 mg of ranitidine intravenously 30-60 minutes before administration of Paclitaxel-LENS®.

The regimen and doses in each individual case should be guided by the data in the literature.

Paclitaxel-LENS® is administered intravenously as a 3-hour or 24-hour infusion at a dose of 135-175 mg/m2 with an interval between courses of 3 weeks. The drug is used as monotherapy or in combination with cisplatin (ovarian cancer and non-small cell lung cancer) or doxorubicin (breast cancer).

The administration of Paclitaxel-LENS® should not be repeated until the neutrophil count is at least 1500/μL of blood and the platelet count is at least 100000/μL of blood.

Patients who have severe neutropenia (neutrophil count < 500/mm3 in blood for 7 days or longer) or severe peripheral neuropathy during subsequent courses of treatment the dose of Paclitaxel-LENS® should be decreased by 20 %.

The drug solution is prepared immediately prior to administration by diluting the concentrate with 0.9% sodium chloride solution or 5% dextrose solution or 5% dextrose solution in 0.9% sodium chloride solution for injection or 5% dextrose solution in Ringer’s solution to a final concentration of 0.3 to 1.2 mg/ml. The prepared solutions may be opalescent due to the carrier base present in the drug form, and the opalescence of the solution remains after filtration.

Paclitaxel-LENS® should be prepared, stored and administered using equipment that does not contain PVC parts.

Paclitaxel-LENS® should be administered through a system with an integrated membrane filter (pore size not greater than 0.22 microns).

Interaction

Special Instructions

The use of Paclitaxel-LENS® should be under the supervision of a physician experienced in the use of antitumor chemotherapeutic agents.

In order to prevent severe hypersensitivity reactions, all patients should be premedicated with glucocorticosteroids, antihistamines and H2 histamine receptor antagonists: 20 mg dexamethasone (or equivalent) orally approximately 12 and 6 hours before administration of Paclitaxel-LENS®, 50 mg diphenhydramine (or equivalent) intravenously, and 300 mg cimetidine or 50 mg ranitidine intravenously 30-60 minutes before administration of Paclitaxel-LENS®.

In case of severe hypersensitivity reactions, the infusion of Paclitaxel-LENS® should be stopped immediately and symptomatic treatment should be initiated and the drug should not be re-injected.

Polyoxyethylated castor oil in Paclitaxel-LENS® may cause extraction of DEHP [di-(2-hexyl)phthalate] from plasticized polyvinyl chloride (PVC) containers, and the degree of DEHP washout increases with increasing solution concentration and with time. Therefore, when preparing, storing and administering Paclitaxel-LENS®, equipment that does not contain PVC parts should be used.

At the time of treatment, peripheral blood count, BP, HR and number of breaths (especially during the first hour of infusion), ECG control (and before the start of treatment) should be regularly monitored.

In cases of development of atrioventricular conduction abnormalities, continuous cardiac monitoring should be performed during repeated infusions.

Patients should use reliable contraceptive methods during treatment with Paclitaxel-LNS® and for at least 3 months after therapy ends.

During treatment it is necessary to refrain from engaging in potentially hazardous activities that require increased concentration and quick psychomotor reactions.

Paclitaxel-LENS® is a cytotoxic agent which should be handled with caution, gloves should be worn and contact with the skin or mucous membranes should be avoided; in these cases the skin should be washed thoroughly with soap and water or (eyes) with plenty of water.

Contraindications

– Hypersensitivity to the drug, as well as to other drugs whose dosage form includes polyoxyethylated castor oil.

– Pregnancy and lactation.

– Baseline neutrophil counts less than 1500/μL in patients with solid tumors.

– Baseline (or recorded during treatment) neutrophil counts less than 1000/μL in patients with Kaposi’s sarcoma in AIDS patients.

Side effects

The frequency and severity of side effects are dose-dependent.

Hematopoietic disorders: neutropenia, thrombocytopenia, anemia.

The suppression of bone marrow function, mainly of the granulocytic sprout, was the main toxic effect limiting the dose of the drug. The maximum decrease in neutrophil levels is usually seen on days 8-11, with normalization occurring on day 22.

Allergic reactions: in the first hours after administration of Paclitaxel-LENS® there may be hypersensitivity reactions manifested by bronchospasm, decreased blood pressure, pain behind the chest, flushing of the face, skin rashes, generalized urticaria, angioedema. Single cases of chills and back pain have been described.

Cardiovascular system: decrease of arterial pressure, rarely – increase of BP, bradycardia, tachycardia, atrioventricular block, changes on ECG, vascular thrombosis and thrombophlebitis are possible.

Respiratory system: interstitial pneumonia, pulmonary fibrosis, pulmonary embolism, and also more frequent development of radiation pneumonitis in patients who simultaneously undergo radiation therapy.

Nervous system disorders: mainly paresthesias. Rarely – grand mal type seizures, visual disturbances, ataxia, encephalopathy, autonomic neuropathy manifested by paralytic bowel obstruction and orthostatic hypotension.

Muscular system disorders: arthralgia, myalgia.

Digestive system disorders: nausea, vomiting, diarrhea, mucositis, anorexia, constipation. There have been single reports of acute intestinal obstruction, intestinal perforation, mesenteric artery thrombosis, ischemic colitis.

Hepatic function: increased activity of “hepatic” transaminases (often ACT), alkaline phosphatase and serum bilirubin. Cases of hepatonecrosis and hepatic encephalopathy have been described.

Local reactions: pain, edema, erythema, induration and pigmentation of the skin at the injection site; extravasation may cause inflammation and necrosis of the subcutaneous tissue.

Skin and skin appendages: alopecia, rarely pigmentation disorders or discoloration of the nail bed.

Other adverse reactions: asthenia and general malaise.

Overdose

Similarities