Paclitaxel

Paclitaxel is an anti-cancer medication used for the treatment of breast cancer, pancreatic cancer and non-small cell lung cancer. It is given as an injection by a qualified medical professional. Your doctor will decide what dose is necessary and how often you need to take it. This will depend on what you are being treated for and may change from time to time. You should take it exactly as your doctor has advised. Taking it in the wrong way or taking too much can cause very serious side effects. It may take several weeks or months for you to see or feel the benefits but do not stop taking it unless your doctor tells you to. Some common side effects of this medicine include nausea, vomiting, and weakness. It may also cause serious side effects such as swelling of hands, lips, hair loss, and weight gain. To reduce these side effects your doctor may suggest some medication along with it. But, inform your doctor if you notice unexplained bruising or bleeding, sore throat, mouth ulcers, high temperature (fever). This medicine may reduce the number of blood cells (decrease red blood and white blood cells) in your blood, thereby, increasing the susceptibility to infections. Regular blood tests are required to check your blood cells and liver function. Before taking it, tell your doctor if you have heart disease, liver, or kidney problems or are taking any medicines to treat infections. Many other medicines can affect, or be affected by, this medicine so let your doctor know all medications you are using. This medicine is not recommended during pregnancy or while breastfeeding. The use of effective contraception by both males and females during treatment is important to avoid pregnancy. Paclitaxel is an anticancer medication. It works by interfering with the microtubule structures which help the cancer cells to divide and multiply. This slows the growth of cancer cells and eventually kills them.

• Breast cancer • Non-small cell lung cancer • Pancreatic cancer

Cytotoxic Chemotherapy, Immunological Chemotherapy

Anti-microtubule agent / Taxane

Paclitaxel promotes the assembly of microtubules from tubulin dimers and stabilizes them by preventing depolymerization, thereby inhibiting vital mitotic cellular functions. Plasma concentrations decline in a biphasic manner following intravenous administration.

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.

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 7.5 mg/dL: Do not administer 3-hr infusion AST/ALT 5 x ULN: Do not administer Child Dose: Safety and efficacy not established

Your doctor or nurse will give you this medicine. Kindly do not self administer.

Chemotherapy schedules must be strictly followed. If a dose is missed, consult your oncologist immediately to reschedule.

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)

[UNSAFE] Paclitaxel may cause side effects which could affect your ability to drive. As there is no reason why you cannot continue driving between courses of Paclitaxel but you should remember that this medicine contains some alcohol and it may be unwise to drive Paclitaxel is an anti-cancer medication used for the treatment of breast cancer, pancreatic cancer, and non-small cell lung cancer. It is given as an intravenous (IV) injection into your vein, usually over 1 hour and every three weeks. Do not take Paclitaxel if you are pregnant or breastfeeding. Use reliable methods of contraception to prevent pregnancy while taking this medicine. Your doctor may get regular blood tests done to monitor your blood cells and liver function during treatment with this medicine. Inform your doctor if you notice unexplained bruising or bleeding, sore throat, mouth ulcers, high temperature (fever) or other signs of infection. Talk to your doctor if you have sudden weight gain or if you have swelling in your arms and legs that doesn't go away.

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.

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.

No specific food interactions have been formally established, but standard healthy nutritional guidelines during chemotherapy apply.

[CONSULT YOUR DOCTOR] Paclitaxel is unsafe to use during pregnancy as there is definite evidence of risk to the developing baby. However, the doctor may rarely prescribe it in some life-threatening situations if the benefits are more than the potential risks. Please consult your doctor.

[UNSAFE] Paclitaxel is unsafe to use during breastfeeding. Data suggests that the drug may cause toxicity to the baby.

Not recommended for use in children below 18 years due to lack of established safety and efficacy data.

Clinical studies indicate similar safety and efficacy profiles in older patients, though greater sensitivity in some older individuals cannot be ruled out. Dose adjustments should be based on tolerance.

[SAFE IF PRESCRIBED] Paclitaxel is safe to use in patients with kidney disease. No dose adjustment of Paclitaxel is recommended. However, talk to your doctor if you have any underlying kidney disease. [CAUTION] Paclitaxel should be used with caution in patients with liver disease. Dose adjustment of Paclitaxel may be needed. Please consult your doctor. Use of Paclitaxel is not recommended in patients with severe liver disease.

There is no known antidote. Overdose symptoms primarily include bone marrow suppression, peripheral neurotoxicity, and mucositis. Monitor closely and provide supportive treatment.

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

Paclitaxel is a complex diterpene pseudoalkaloid possessing a taxane ring system with an oxetane ring and an ester side chain.