PACLITAXEL

PACLITAXEL
(pac-li-tax'el)
Abraxane, Taxol
Classifications: antineoplastic; taxane;
Therapeutic: antineoplastic

Pregnancy Category: D

Availability

6 mg/mL injection; 100 mg powder for injection (with 900 mg human albumin)

Action

Normal functioning microtubules within a cell are essential for cell shape and organelles present within cells. Paclitaxel is an antimicrotubular agent that interferes with the microtubule network essential for interphase and mitosis. Induces abnormal spindle formation and multiple asters during mitosis.

Therapeutic Effect

Interferes with growth of rapidly dividing cells including cancer cells, and eventually causes cell death.

Uses

Ovarian cancer, breast cancer, Kaposi's sarcoma, non-small cell lung cancer (NSCLC).

Unlabeled Uses

Other solid tumors, leukemia, melanoma.

Contraindications

Taxol: hypersensitivity to paclitaxel, or taxane; baseline neutrophil count <1500 cells/mm3; thrombocytopenia; with AIDS-related Kaposi sarcoma baseline neutrophil count <1000 cells/mm3. For Abraxane: baseline neutrophil count <1500 cells/mm3; pregnancy (category D), lactation.

Cautious Use

Cardiac arrhythmias, cardiac disease; impaired liver function; alcoholism; older adults; peripheral neuropathy. Safety and efficacy in children are not established.

Route & Dosage

Ovarian Cancer, NSCLC
Adult: IV 135 mg/m2 24-h infusion repeated q3wk

Breast Cancer
Adult: IV 175–250 mg/m2 over 3 h q3wk
Abraxane: IV 260 mg/m2 over 30 min q3wk

Kaposi's Sarcoma
Adult: IV 135 mg/m2 infused over 3 h q3wk or 100 mg/m2 infused over 3 h q2wk

Administration

Intravenous
  • Note: Premedication as follows (except with Abraxane) to avoid severe hypersensitivity: dexamethasone 20 mg (10 mg with AIDS-related Kaposi's) PO/IV at 12 & 6 h prior to infusion; diphenhydramine 50 mg IV 30–60 min prior to infusion; and cimetidine 300 mg or ranitidine 50 mg IV 30 min before infusion.
  • Do not administer to patients with AIDS-related Kaposi's unless neutrophil count is at least 1000/mm3; for all others, do not administer unless neutrophil count is at least 1500/mm3.
  • Follow institutional or standard guidelines for preparation, handling, and disposal of cytotoxic agents.

PREPARE: IV Infusion: Dilution of Conventional Paclitaxel: Do not use equipment or devices containing polyvinyl chloride (PVC) in preparation of infusion. Dilute to a final concentration of 0.3–1.2 mg/mL in any of the following: D5W, NS, D5/NS, or D5W in Ringer's injection. The prepared solution may be hazy, but this does not indicate a loss of potency. ?? Abraxane Vial Reconstitution: Slowly inject 20 mL NS over at least 1 min onto the inside wall of the vial to yield 5 mg/mL.?? DO NOT inject directly into the cake powder. Allow vial to sit for at least 5 min, then gently swirl for at least 2 min to completely dissolve. If foaming occurs, let stand for at least 15 min until foam subsides.??If particulates or settling are visible, gently invert vial to ensure complete resuspension prior to use. ??Remove the required dose and inject into an empty sterile, PVC or non-PVC type IV bag. 

ADMINISTER: IV Infusion: Because tissue necrosis occurs with extravasation, frequently assess patency of a peripheral IV site. ?? Conventional Paclitaxel: Infuse over 3 h through IV tubing containing an in-line (0.22 micron or less) filter. Do not use equipment containing PCV.?? Abraxane: DO NOT use an in-line filter. Infuse over 30 min. 

INCOMPATIBILITIES Solution/additive: PVC bags and infusion sets should be avoided (except with Abraxane) due to leaching of DEHP (plasticizer). Do not mix with any other medications. Y-site: Amphotericin B, amphotericin B cholesteryl sulfate complex, chlorpromazine, doxorubicin liposome, hydroxyzine, methylprednisolone, mitoxantrone.

  • Conventional paclitaxel solutions diluted for infusion are stable at room temperature (approximately 25° C/77° F) for up to 27 h. Reconstituted Abraxane should be used immediately but may be kept refrigerated for up to 8 h if needed.

Adverse Effects (≥1%)

CV: Ventricular tachycardia, ventricular ectopy, transient bradycardia, chest pain. CNS: Fatigue, headaches, peripheral neuropathy, weakness, seizures. GI: Nausea, vomiting, diarrhea, taste changes, mucositis, elevations in serum triglycerides. Hematologic: Neutropenia, anemia, thrombocytopenia. Body as a Whole: Hypersensitivity reactions (hypotension, dyspnea with bronchospasm, urticaria, abdominal and extremity pain, diaphoresis, angioedema), myalgias, arthralgias, alopecia. Skin: Alopecia, tissue necrosis with extravasation. Urogenital: Minor elevations in kidney and liver function tests.

Interactions

Drug: Increased myelosuppression if cisplatin, doxorubicin is given before paclitaxel; ketoconazole can inhibit metabolism of paclitaxel; additive bradycardia with beta blockers, digoxin, verapamil; additive risk of bleeding with anticoagulants, nsaids, platelet inhibitors (including aspirin), thrombolytic agents.

Pharmacokinetics

Distribution: >90% protein bound; does not cross CSF. Metabolism: In liver (CYP3A4, 2C8). Elimination: Feces 70%, urine 14%. Half-Life: 1–9 h.

Nursing Implications

Assessment & Drug Effects

  • Monitor for hypersensitivity reactions, especially during first and second administrations of the paclitaxel. S&S requiring treatment, but not necessarily discontinuation of the drug, include dyspnea, hypotension, and chest pain. Discontinue immediately and manage symptoms aggressively if angioedema and generalized urticaria develop.
  • Monitor vital signs frequently, especially during the first hour of infusion. Bradycardia occurs in approximately 12% of patients, usually during infusion. It does not normally require treatment. Cardiac monitoring is indicated for those with severe conduction abnormalities.
  • Lab tests: Monitor hematologic status throughout course of treatment. Severe neutropenia is common but usually of short duration (less than 500/mm3 for less than 7 d) with the nadir occurring about day 11. Thrombocytopenia occurs less often and is less severe with the nadir around day 8 or 9. The incidence and severity of anemia increase with exposure to paclitaxel.
  • Monitor for peripheral neuropathy, the severity of which is dose dependent. Severe symptoms occur primarily with higher than recommended doses.

Patient & Family Education

  • Immediately report to physician S&S of paclitaxel hypersensitivity: difficulty breathing, chest pain, palpitations, angioedema (subcutaneous swelling usually around face and neck), and skin rashes or itching.
  • Be sure to have periodic blood work as prescribed.
  • Avoid aspirin, NSAIDs, and alcohol to minimize GI distress.
  • Be aware of high probability of developing hair loss (>80%).

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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