Special Warning : אזהרת שימוש

WARNINGS

PACLIAVENIR SOLUTION FOR INJECTION (paclitaxel) should be administered under the supervision of a physician experienced in the use of cancer chemotherapy agents.

Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration

PACLIAVENIR SOLUTION FOR INJECTION should be administered as a diluted infusion. Patients receiving PACLIAVENIR SOLUTION 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, PACLIAVENIR SOLUTION FOR INJECTION infusion should be discontinued immediately and the patient should not be rechallenged with the drug (see ADVERSE REACTIONS).
Patients should be observed closely during the initial cycles of treatment. Appropriate supportive therapies should be readily available in case of a severe hypersensitivity reaction.
PACLIAVENIR SOLUTION FOR INJECTION should not be administered to patients with baseline neutrophil counts of less than 3
1,500 cells/mm . 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 PACLIAVENIR SOLUTION FOR INJECTION treatment. Patients should not be retreated with 3 subsequent cycles of PACLIAVENIR SOLUTION FOR INJECTION until neutrophils recover to a level >1,500 cells/mm , and 3 platelets recover to a level >100,000 cells/mm (see DOSAGE AND ADMINISTRATION).

Paclitaxel should be given before a platinum compound when it is .given in combination with a platinum compound.

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 PACLIAVENIR SOLUTION FOR INJECTION (see ADVERSE REACTIONS).

Moderate to severe mucositis is uncommon with the recommended dose and schedule of paclitaxel. However, if treatment is to be continued in the event of moderate or severe reactions, the dose of paclitaxel should be reduced for subsequent courses of paclitaxel therapy. In KS patients, severe mucositis is rare. If severe reactions occur, the paclitaxel dose should be reduced by 25%.

Use in Pregnancy

PACLIAVENIR SOLUTION 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 PACLIAVENIR SOLUTION FOR INJECTION.

Nursing Mothers

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

Fertility
Male patients should seek advice regarding cryoconservation of sperm prior to treatment with paclitaxel because of the possibility of infertility.

Use in Children

The safety and effectiveness of PACLIAVENIR SOLUTION FOR INJECTION in pediatric patients have not been established.
PRECAUTIONS

Undiluted concentrate should not come in contact with plasticized polyvinyl chloride (PVC) equipment. In order to minimize patient exposure to the plasticizer DEHP [di-(2-ethylhexyl)phthalate)], which may leach from PVC infusion bags or sets, diluted PACLIAVENIR SOLUTION FOR INJECTION (paclitaxel) solutions should preferably be stored in glass bottles and administered through polyethylene-lined administration sets.

Cardiovascular

Hypotension, hypertension and bradycardia have been observed during PACLIAVENIR SOLUTION 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 PACLIAVENIR SOLUTION FOR INJECTION infusion is recommended. Continuous cardiac monitoring is not required except for patients who develop serious conduction abnormalities (see WARNINGS, ADVERSE REACTIONS).

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 PACLIAVENIR SOLUTION FOR INJECTION for moderate to severe neuropathy (see ADVERSE REACTIONS, DOSAGE AND ADMINISTRATION).

Hepatic

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

Other

A combination of pulmonary radiotherapy and paclitaxel treatment (irrespective of the order of the treatments) may promote the development of interstitial pneumonitis.

Gastrointestinal
Pseudomembranous colitis has been rarely reported including cases in patients who have not been concomitantly treated with antibiotics. This reaction should be considered in the differential diagnosis of cases of severe or persistent diarrhoea occurring during or shortly after treatment with paclitaxel.

Effects on Driving