Paclitaxel: Indication, Dosage, Side Effect, Precaution

Generic Medicine Info Patient Medicine Information

This information is not country-specific. Please refer to the Malaysia prescribing information.

Generic Medicine Info

Indications and Dosage

Intravenous
Metastatic breast cancer

Adult: As albumin bound paclitaxel nanoparticles: 260 mg/m² over 30 minutes every 3 weeks. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).

Intravenous
Breast cancer

Adult: As 6 mg/mL conventional solution: Adjuvant therapy in patient with node-positive cases following anthracycline-containing regimen: 175 mg/m² infused over 3 hours once every 3 weeks for 4 cycles. 1st line treatment in combination with doxorubicin: 220 mg/m² via infusion over 3 hours once every 3 weeks. 2nd line treatment as monotherapy: 175 mg/m² via infusion over 3 hours once every 3 weeks. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).

Intravenous
HER2-overexpressing advanced or metastatic breast cancer

Adult: As 6 mg/mL conventional solution in combination with trastuzumab: 175 mg/m² infused over 3 hours once every 3 weeks. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).

Intravenous
Advanced ovarian carcinoma

Adult: As conventional 6 mg/mL solution: Primary treatment in combination with cisplatin: 175 mg/m²infused over 3 hours every 3 weeks. Alternatively, 135 mg/m² infused over 24 hours, repeated at 3-week intervals. Secondary treatment as monotherapy: 175 mg/m² infused over 3 hours once every 3 weeks. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).

Intravenous
Locally advanced non-small cell lung carcinoma, Metastatic non-small cell lung carcinoma

Adult: As albumin bound paclitaxel nanoparticles in combination with carboplatin: 100 mg/m² infused over 30 minutes, on days 1, 8, and 15 of a 21-day cycle. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).

Intravenous
Advanced non-small cell lung cancer

Adult: As 6 mg/mL conventional solution in combination with cisplatin: 175 mg/m² infused over 3 hours or 135 mg/m² over 24 hours, repeated at 3-week intervals. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).

Intravenous
Metastatic adenocarcinoma of pancreas

Adult: As albumin bound paclitaxel nanoparticles in combination of gemcitabine: 125 mg/m² over 30 minutes on days 1, 8 and 15 of a 28-day cycle. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).

Intravenous
AIDS-related Kaposi's sarcoma

Adult: As 6 mg/mL conventional solution: 100 mg/m² infused over 3 hours every 2 weeks. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).

Hepatic Impairment

Advanced ovarian carcinoma; Breast cancer; HER2 overexpressing advanced or metastatic breast cancer; AIDS-related Kaposi's sarcoma:
Severe: Contraindicated.

Metastatic breast carcinoma; Locally advanced or metastatic non-small cell lung carcinoma; Metastatic adenocarcinoma of pancreas:
Moderate to severe: Reduce dose by 20%.

Reconstitution

Dilute vials labelled as containing 6 mg/mL solution with NaCl 0.9% or dextrose 5% inj to final concentration of 0.3-1.2 mg/mL. Reconstitute albumin-bound nanoparticles lyophilised powder labelled as containing 100 or 250 mg slowly with 20 mL or 50 mL NaCl 0.9% solution respectively, over a minimum of 1 minute. Inject diluents onto the inside wall of the vial to prevent foaming. Allow the vial to stand for 5 minutes then gently swirl or invert for at least 2 minutes until complete resuspension occurs.

Contraindications

Solid tumours in patients with baseline neutrophil counts <1500 cells/mm³. Kaposi sarcoma in patients with baseline neutrophil <1000 cells/mm³ and serious uncontrolled infection. Severe hepatic impairment (as conventional solution). Lactation.

Special Precautions

Patient with pre-existing neuropathies, conduction abnormalities. Hepatic impairment. Elderly. Pregnancy. Premedication with corticosteroid, antihistamine and histamine H₂-receptor antagonist may be required to reduce risk of hypersensitivity reaction.

Adverse Reactions

Significant: Bone marrow suppression (e.g. neutropenia); hypotension, hypertension, bradycardia; extravasation, injection site reactions; sensory/peripheral neuropathy. sepsis, nausea, vomiting, diarrhoea. Rarely, conduction abnormalities, CHF, left ventricular dysfunction.
Blood and lymphatic system disorders: Anaemia, leukopenia, thrombocytopenia, febrile neutropenia.
Cardiac disorders: Tachycardia, arrhythmia, supraventricular tachycardia, chest pain, bradycardia, dyspnoea.
Eye disorders: Increased lacrimation, blurred vision.
Gastrointestinal disorders: Constipation, stomatitis, abdominal pain and distension.
General disorders and admin site conditions: Fatigue, asthenia, pyrexia, malaise, ataxia.
Infections and infestations: Candidiasis, conjunctivitis.
Injury, poisoning and procedural complications: Injection site reactions (including pain, erythema, localised oedema, induration).
Investigations: Increased AST, gamma-glutamyltransferase, blood alkaline phosphatase, serum creatinine; ECG abnormality.
Metabolism and nutrition disorders: Anorexia, dehydration, oedema.
Musculoskeletal and connective tissue disorders: Arthralgia, myalgia, back pain.
Nervous system disorders: Paraesthesia, headache, dizziness, vertigo.
Renal and urinary disorders: UTI.
Respiratory, thoracic and mediastinal disorders: Upper respiratory tract infection, cough, pulmonary embolism.
Skin and subcutaneous tissue disorders: Alopecia, rash, pruritus, erythema, nail discolouration, skin hyperpigmentation, nail changes.
Vascular disorders: Flushing, hypertension, hypotension, venous thrombosis.
Potentially Fatal: Anaphylaxis and severe hypersensitivity reactions, pneumonitis.

Pregnancy Category (US FDA)

IV/Parenteral: D

Patient Counseling Information

This drug may cause mild tiredness and dizziness, if affected, do not drive or operate machinery.

Monitoring Parameters

Monitor CBC with differential and platelet count; LFT, kidney function; vital signs (frequently during the 1st hour of infusion); cardiac function; infusion site during infusion.

Drug Interactions

Increased plasma concentration and toxicity with CYP2C8 and CYP3A4 inhibitors (e.g. ketoconazole, erythromycin, fluoxetine, clopidogrel, cimetidine, ritonavir). Decreased plasma concentration and efficacy with CYP2C8 and CYP3A4 inducers (e.g. rifampicin, carbamazepine, phenytoin, efavirenz).

Action

Description:
Mechanism of Action: Paclitaxel is an antineoplastic taxane derivative, originally derived from Pacific yew tree, Taxus brevifolia, and currently obtained semisynthetically from the needles of European yew, Taxus baccata. It promotes microtubule formation by enhancing the action of tubulin dimers, stabilising existing microtubules, and inhibiting their disassembly, interfering with the late G₂ mitotic phase and inhibiting cell replication. It also suppresses cell proliferation and regulate immune response.
Pharmacokinetics:
Distribution: Widely distributed into tissues and body fluids. Volume of distribution: 227-688 L/m² (24-hour infusion). Plasma protein binding: 89-98%.
Metabolism: Metabolised in the liver by CYP2C8 and CYP3A4 enzymes to 6α-hydroxypaclitaxel metabolite.
Excretion: Via faeces (approx 71%; approx 5% as unchanged drug); urine (approx 14%).

Chemical Structure

Storage

Store below 25°C. Protect from light. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.

MIMS Class

Cytotoxic Chemotherapy

ATC Classification

L01CD01 - paclitaxel ; Belongs to the class of taxanes from plant alkaloids and other natural products. Used in the treatment of cancer.

References

Abraxane (Abraxis BioScience, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 03/04/2019.

Anon. Paclitaxel. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 03/04/2019.

Buckingham R (ed). Paclitaxel. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/04/2019.

Paclitaxel (Fresenius Kabi USA, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 03/04/2019.

Paclitaxel. Drugs and Lactation Database (LactMed) [Internet]. Bethesda, MD. U.S. National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK501922/. Accessed 05/04/2019.

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