Paclitaxel for Injection Information for Practitioners and Medical Professionals

Notice of Compliance

In 1994, the Canadian Federal Health Protection Branch (HPB) authorized the use of clinical trials to test Paclitaxel for Injection. In September 2001, a Notice of Compliance was issued, marketing authorization for Paclitaxel for Injection was approved based on the proven effectiveness shown during clinical studies in Canada.

Paclitaxel Drug Mechanism and Molecular Structure

Taxanes are a group of naturally occurring molecules known for their cancer-fighting properties. Paclitaxel is a polyoxygenated diterpene with a lateral branch, and has a unique method of action. Essentially, it interferes with the division and proliferation of cells, by affecting the polymerization of tubulin in microtubules during cell mitosis.

Normally during cell division, the microtubules are broken down into their constituent parts of a-tubulin, B-tubulin, and the MAPs (microtubule-associated proteins). With sufficient decomposition of the microtubules, a critical concentration of tubulin is reached, signalling their re-assembly into a new structure, permitting the cell to complete division. Paclitaxel stabilizes the composition of the microtubules, preventing them from decomposing. As a result, the concentration of free tubulin remains below the critical level, the mitotic spindle cannot re-assemble itself, the cell can no longer divide, and eventually dies.

Product Information

Biolyse Pharma Paclitaxel is a natural molecule extracted from the twigs and needles of Taxus canadensis. This plant is the predominant representative of the Taxacea family in Northeastern America and is closely related to Taxus brevifolia prevailing in Northwestern America. Taxus canadensis is an evergreen shrub growing in a natural environment and is free of any herbicide or pesticide when harvested.

Detailed product information is available in our monograph. Below you will find an overview that may help you to determine whether Paclitaxel for Injection is suitable for your patient.

PACLITAXEL FOR INJECTION (paclitaxel) is contraindicated in patients who have a history of severe hypersensitivity reactions to paclitaxel or other drugs formulated in Cremophor EL (polyethoxylated castor oil).

PACLITAXEL FOR INJECTION should not be used in patients with severe baseline neutropenia (<1,500 cells/mm3) ADMINISTRATION INFORMATION Paclitaxel for Injection (paclitaxel) should be administered under the supervision of a physician experienced in the use of cancer chemotherapy agents. PACLITAXEL FOR INJECTION should be administered as a diluted infusion. Patients receiving PACLITAXEL FOR INJECTION should be pretreated with corticosteroids, antihistamines, and H2 antagonists (such as dexamethasone, diphenhydramine and cimetidine or ranitidine) to minimize hypersensitivity reactions (see DOSAGE AND ADMINISTRATION). Anaphylaxis, and severe hypersensitivity reactions characterized by dyspnea and hypotension requiring treatment, angioedema, and generalized urticaria have occurred in patients receiving paclitaxel. These reactions are probably histamine-mediated. Literature reports indicate that rare fatal reactions have occurred in patients despite pre-treatment. In case of a severe hypersensitivity reaction, PACLITAXEL FOR INJECTION infusion should be discontinued immediately and the patient should not be rechallenged with the drug. PACLITAXEL FOR INJECTION should not be administered to patients with baseline neutrophil counts of less than 1,500 cells/mm3. Bone marrow suppression (primarily neutropenia) is dose and schedule dependent and is the dose-limiting toxicity within a regimen. Neutrophil nadirs occurred at a median of 11 days. Frequent monitoring of blood counts should be instituted during PACLITAXEL FOR INJECTION treatment. Patients should not be retreated with subsequent cycles of PACLITAXEL FOR INJECTION until neutrophils recover to a level >1,500 cells/mmł and platelets recover to a level >100,000 cells/mm3.

Severe cardiac conduction abnormalities have rarely been reported during paclitaxel therapy. If patients develop significant conduction abnormalities during administration, appropriate therapy should be administered and continuous electrocardiographic monitoring should be performed during subsequent therapy with PACLITAXEL FOR INJECTION.

Use in Pregnancy

PACLITAXEL FOR INJECTION may cause fetal harm when administered to a pregnant woman. Paclitaxel has been shown to be embryototic and fetotoxic in rabbits and to decrease fertility in rats. There are no studies in pregnant women. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with PACLITAXEL FOR INJECTION.

Nursing Mothers

It is not known whether PACLITAXEL FOR INJECTION is excreted in human milk. Breast feeding should be discontinued for the duration of PACLITAXEL FOR INJECTION therapy.

Use in Children

The safety and effectiveness of PACLITAXEL FOR INJECTION in pediatric patients have not been established.

Cardiovascular

Hypotension, hypertension and bradycardia have been observed during PACLITAXEL FOR INJECTION (paclitaxel) administration; patients are usually asymptomatic and generally do not require treatment. In severe cases paclitaxel infusions may need to be interrupted or discontinued at the discretion of the treating physician. Frequent monitoring of vital signs, particularly during the first hour of PACLITAXEL FOR INJECTION infusion is recommended. Continuous cardiac monitoring is not required except for patients who develop serious conduction abnormalities.

Nervous System

Although the occurrence of peripheral neuropathy is frequent, the development of severe symptomatology is unusual. A dose reduction of 20% is recommended for all subsequent courses of PACLITAXEL FOR INJECTION for moderate to severe neuropathy.

Hepatic

There is evidence that the toxicity of PACLITAXEL FOR INJECTION is enhanced in patients with increased liver enzymes. Caution should be exercised when administering PACLITAXEL FOR INJECTION to patients with moderate to severe hepatic impairment and dose adjustments should be considered.

Drug Interactions

The metabolism of paclitaxel is catalysed by cytochrome P450 isoenzymes CYP 3A4 and CYP 2C8. Caution should be exercised when administering paclitaxel concominently with known substrates, inducers or inhibitors of these isoenzymes.

Driving/Operating Machinery

Since PACLITAXEL FOR INJECTION contains ethanol, consideration should be given to the possibility of CNS and other effects.

Hypersensitivity Reactions

Dyspnea, flushing, chest pain and tachycardia were the most frequent signs and symptoms of hypersensitivity reactions. These reactions occurred generally in early treatment courses and within the first hour of infusion. Detailed information concerning hypersensitivity reactions is available in our product monograph.

The product monograph for Paclitaxel is available upon request.