Uses of Xelpac: - Breast cancer - Non-small cell lung cancer - Pancreatic cancer Ovarian carcinoma, Breast cancer, Lung cancer, Kaposi's sarcoma History of hypersensitivity (especially macrogol glycerol ricinolate). Patients with baseline neutropenia of <1500 cells/mm3 (<1000 cells/mm3 for kaposi's sarcoma). Pregnancy and lactation. In kaposi's sarcoma, contraindicated in patients with concurrent, serious, uncontrolled infections.

Cytotoxic Chemotherapy

Paclitaxel promotes microtubule formation by enhancing the action of tubulin dimers, stabilising existing microtubules and preventing their disassembly, thereby disrupting normal cell division in the late G2 mitotic phase of the cell cycle. This results in the inhibition of cell replication.

How to use Paclitaxel: Your doctor or nurse will give you this medicine. Kindly do not self administer. Administration: Reconstitution: Paclitaxel must be diluted before infusion. It can be diluted in 0.9% sodium chloride inj, 5% dextrose inj, 5% dextrose and 0.9% sodium chloride inj or 5% dextrose in lactated Ringer's inj to a concentration of 0.3-1.2 mg/ml. Adult Dose: Intravenous Ovarian carcinoma Adult: Primary treatment (in combination with cisplatin or carboplatin): 135 mg/m2 infused over 24 hr followed by cisplatin and repeated at 3 wk intervals. Secondary treatment (as single agent): 135 or 175 mg/m2 infused over 3 hr once every 3 wk. Breast cancer Adult: Adjuvant therapy; 2nd line monotherapy or 1st line treatment with trastuzumab: 175 mg/m2 infused over 3 hr once every 3 wk for 4 courses; when used with trastuzumab, dose should be given the day after the 1st dose of trastuzumab or immediately after subsequent doses if well-tolerated. 1st line with doxorubicin: 220 mg/m2 over 3 hr every 3 wk, dose to be administered 24 hr after doxorubicin. Advanced non-small cell lung cancer Adult: 135 mg/m2 over 24 hr or 175 mg/m2 over 3 hr, followed by cisplatin and repeated at 3 wk intervals. AIDS-related Kaposi's sarcoma Adult: 135 mg/m2 over 3 hr every 3 wk. Alternatively, 100 mg/m2 over 3 hr every 2 wk especially in patients with poor performance status. Hepatic Impairment With solid carcinomas and not Kaposi sarcoma 24-hr infusion AST/ALT <2 x ULN and bilirubin ?1.5 mg/dL: 135 mg/m² over 24 hr AST/ALT 2-<10 x ULN and bilirubin ?1.5 mg/dL: 100 mg/m² over 24 hr AST/ALT <10 x ULN and bilirubin 1.6-7.5 mg/dL: 50 mg/m² over 24 hr AST/ALT ?10 x ULN OR bilirubin >7.5 mg/dL: Do not administer 3-hr infusion AST/ALT <10 x ULN and bilirubin <1.25 x ULN: 175 mg/m² over 3 hr AST/ALT <10 x ULN and bilirubin 1.26-2 x ULN: 135 mg/m² over 3 hr AST/ALT <10 x ULN and bilirubin 2.01-5 x ULN: 90 mg/m² over 3 hr AST/ALT ?10 x ULN OR bilirubin >5 x ULN: Do not administer Child Dose: Safety and efficacy not established

Myelosuppression was more profound when given after cisplatin than with the alternate sequence (e.g., paclitaxel before cisplatin). CYP2C8 inducers e.g. carbamazepine, phenobarbital, phenytoin, rifampicin, rifapentine, and secobarbital may reduce levels or effects. CYP2C8 inhibitors e.g. gemfibrozil, ketoconazole, montelukast, and ritonavir may increase levels or effects. CYP3A4 inducers e.g. aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins may decrease the levels or effects. CYP3A4 inhibitors e.g. azole antifungals, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, telithromycin, and verapamil may increase levels or effects. May increase anthracycline (eg doxorubicin, epirubicin) levels or toxicity; admin of anthracycline at least 24 hr prior to paclitaxel may reduce interaction. May decrease the absorption of cardiac glycosides (may only affect digoxin tablets); levels should be monitored.

History of hypersensitivity (especially macrogol glycerol ricinolate). Patients with baseline neutropenia of <1500 cells/mm3 (<1000 cells/mm3 for kaposi's sarcoma). Pregnancy and lactation. In kaposi's sarcoma, contraindicated in patients with concurrent, serious, uncontrolled infections.

Common - Nausea - Vomiting - Weakness - Low blood platelets - Rash - Upper respiratory tract infection - Urinary tract infection - Bleeding - Anemia (low number of red blood cells) - Flushing (sense of warmth in the face, ears, neck and trunk) - Hair loss - Decreased blood pressure - Peripheral neuropathy (tingling and numbness of feet and hand) - Diarrhea - Decreased white blood cell count (neutrophils) >10% Neutropenia (78-100%),Alopecia (55-96%),Anemia (47-96%),Arthralgia/myalgia (93%),Diarrhea (90%),Leukopenia (90%),Nausea/vomiting (9-88%),Opportunistic infections (76%),Peripheral neuropathy (42-79%),Thrombocytopenia (4-68%),Mucositis (5-45%),Hypersensitivity (2-45%),Renal impairment (34%),Hypotension (17%) 1-10% Bradycardia (3%) <1% Grand mal seizures,Cardiac conduction abnormalities Frequency Not Defined Pyrexia,Dehydration,Pancytopenia,Congestive heart failure,Left ventricular dysfunction,Stevens-Johnson syndrome, toxic epidermal necrolysis, and extravasation Potentially Fatal: Infections and infestations leading to death e.g. pneumonia and peritonitis.

Category D: There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Precaution: Bone marrow suppression during therapy. Monitor cardiac function if conduction abnormalities result. Premedicaton (with corticosteroid, antihistamine and histamine H2-receptor antagonist) may be required to reduce risk of hypersensitivity reaction. Discontinue, if severe reactions e.g. hypotension, dyspnoea, angioedema or urticaria occur. Caution in patients with moderate hepatic impairment. Monitor for reactions of admin. Safety and efficacy in paediatric patients have not been established. Administer before platinum derivatives (cisplatin, carboplatin) if used in combination. Hazardous agent; use appropriate precautions for handling and disposal. Lactation: not known if excreted in breast milk, do not nurse

There is no known antidote for paclitaxel overdose. In case of overdose, the patient should be closely monitored. Treatment should be directed at the primary anticipated toxicities, which consist of bone marrow suppression, peripheral neurotoxicity and mucositis. Overdoses in paediatric patients may be associated with acute ethanol toxicity.

Keep in a dry place and store below 30°C. Protect from light and keep out of the reach of children. Use only freshly prepared solution.

Paclitaxel promotes microtubule formation by enhancing the action of tubulin dimers, stabilising existing microtubules and preventing their disassembly, thereby disrupting normal cell division in the late G2 mitotic phase of the cell cycle. This results in the inhibition of cell replication.

Pregnancy Category D. There is no adequate data from the use of paclitaxel in pregnant women, however as with other cytotoxic medicinal products, paclitaxel may cause foetal harm when administered to pregnant women. Paclitaxel is contraindicated during lactation.