Brand Name: TESU
Chemical Name: 5β,20-Epoxy-1,2α,4,7β,10β,13α-hexahydroxytax-11-en-9-one-4,10-diacetate 2-benzoate 13-ester with (2’R, 3’S)-N-benzoyl-3-phenylisoserine.

【Description】Paclitaxel Injection is a colorless or slightly yellow viscous and clear liquid.

【Pharmacology & Toxicology】Paclitaxel is a new antimicrotubule antineoplactic agent. It promotes microtubule assembly, inhibits depolymerization, maintains microtubule protein stable and inhibits cells mitoses. Paclitaxel can enhance the effects of ionizing radiation in vitro, possibly by blocking cells in the G2 phase and M phase, in which cells are most radiosensitive.

【Pharmacokinetics】Plasma concentrations following IV administration of Paclitaxel appeared in a biphasic manner. 89-98% of Paclitaxel is bound to plasma proteins. Paclitaxel is extensively metabolized in the liver. Paclitaxel and its metabolites are excreted principally (>90%) in the feces via biliary elimination. 1～8% of clearance of Paclitaxel is excreted via urinary excretion. The effect of renal and/or hepatic impairment on the elimination of Paclitaxel has not been fully established.

【Indications】Paclitaxel Injection is indicated for initial and/or subsequent therapy of ovarian cancer, breast cancer and non-small-cell lung cancer. It also can be used for the treatment of head & neck cancer, esophageal cancer, seminoma and Non-Hodgkin’s Lymphomas, etc.

【Dosage & Administration】To prevent severe hypersensitivity reactions, the manufacturer recommends a premedication regimen that includes oral dexamethasone 10 mg administered approximately 12 and 6 hours before Paclitaxel as well as IM diphenhydramine hydrochloride 20 mg and either IV cimetidine hydrochloride (300 mg of cimetidine) or ranitidine hydrochloride (50 mg of ranitidine) administered 30–60 minutes before Paclitaxel. Paclitaxel doses of 135～200 mg/m2 by IV infusion should be administered for monotherapy. When used in combination with granulocyte colony-stimulating factor (G-CSF), Paclitaxel doses of 250 mg/m2 can be administered. Prior to IV infusion, Paclitaxel for injection concentrate must be diluted with sodium chloride injection or 5% dextrose and sodium chloride. It can be administered by 3-hour IV infusion. When used in combination with other agents, Paclitaxel doses of 135～175 mg/m2 by IV infusion should be administered every 3～4 weeks.

【Adverse Effects】Hypersensitivity reactions: Reactions occurred in 39% of patients receiving Paclitaxel therapy, and severe reactions occurred in only 2% of them. Most hypersensitivity reactions belong to I-type allergy, the most frequent manifestations being dyspnea, urticarial rash, hypotension. Almost all of the hypersensitivity reactions occurred within the initial 10 minutes after Paclitaxel administration.
Bone marrow suppression: The major and dose-limiting adverse effect of Paclitaxel is bone marrow suppression, manifested by neutropenia, less frequently thrombocytopenia. It occurs commonly by 8～10 days after administration. Severe neutropenia occurred in 47% of patients during Paclitaxel administration, and severe thrombocytopenia occurred in 5%. Anemia occurred commonly.

Nervous System Effects: Peripheral neuropathy was reported in 62% of patients receiving Paclitaxel manifesting as mild numbness and paresthesia. Severe nervous system toxicity was reported in 6%.

Cardiovascular effects: Hypotensionand bradycardia are the most common adverse cardiovascular effects of Paclitaxel. Arthralgia and/or myalgia, usually consisting of pain in the large joints of the arms and legs, occurred in 55% of patients receiving Paclitaxel. The frequency and severity of arthralgia and/or myalgia were dose dependent.

GI Effects: Nausea, vomiting, diarrhea, and mucositis occurred in 59%, 43% and 39% of patients. Adverse GI effects of Paclitaxel usually are mild to moderate in severity at presently recommended dosages.

Hepatic Effects: increased serum ALT, serum AST, and AKP occurred.

Dermatologic Effects: Alopecia occurred in 80% of patients receiving Paclitaxel.

Local Effects: Injection site reactions, including reactions secondary to extravasation, usually were mild at the injection site.

【Contraindications】

Paclitaxel is contraindicated in patients with known hypersensitivity to Cremophor EL （polyethoxylated castor oil）. Paclitaxel therapy generally should not be administered to patients with baseline neutrophil counts less than 1500/mm3.

【Precautions】

Patients should be pretreated with dexamethasone, diphenhydramine, and H2-receptor antagonists before receiving Paclitaxel.

【Pregnancy, Fertility, and Lactation】

Pregnant women are contraindicated with Paclitaxel for reproduction studies in animals revealed evidence of embryotoxicity. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with Paclitaxel.

【Drug Interactions】

Pharmacokinetics study show that administration of cisplatin followed by Paclitaxel decreases paclitaxel clearance by approximately 30%. Bone marrow suppression would be more severe. Results of in vitro studies show that the metabolism of Paclitaxel was inhibited by ketoconazole.

【Overdose & Toxicity】

There is no known specific antidote for Paclitaxel overdosage. Overdosage with Paclitaxel would be expected to produce effects such as myelosuppression, peripheral neurotoxicity and mucositis.

【Specification】 5ml:30mg
【Storage】Sealed, away from light, and under 25℃.
【Package】1 Vial/carton
【Shelf-life】Temporary 2 years
【Ratification No.】Guo Yao Zhun Zi H10980170