Paclitaxel

Indications

Paclitaxel is used for: Ovarian carcinoma, Breast cancer, Lung cancer, Kaposi's sarcoma

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

Renal Dose

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.

Contra Indications

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.

Precautions

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

Pregnancy-Lactation

Interactions

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.

Adverse Effects

Side effects of Paclitaxel : >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.

Mechanism of Action

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.