Names and pronunciation
Abraxane
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Drug reference
Abraxane
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Func. class.: Antineoplastic— miscellaneous
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Chem. class.: Taxane
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Do not confuse: PACLitaxel/PARoxetine/Paxil
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ACTION: Inhibits reorganization of microtubule network needed for interphase and mitotic cellular functions; causes abnormal bundles of microtubules during cell cycle and multiple esters of microtubules during mitosis
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USES: PACLitaxel: metastatic carcinoma of the ovary, breast; AIDS- related Kaposi’s sarcoma (2nd-line), non–small-cell lung cancer (1st-line), adjuvant treatment for node-positive breast cancer, prostate cancer, esophageal cancer, melanoma PACLitaxel Protein Bound Parti cles: metastatic breast cancer after failure or relapse, metastatic pancre- atic adenocarcinoma refractory prostate cancer, bladder cancer
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Unlabeled uses: (Paclitaxel) endo- metrial, penile cancer
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CONTRAINDICATIONS: Preg nancy; hypersensitivity to PACLitaxel or other products with polyoxyethylated castor oil, albumin Black Box Warning: Neutropenia <1500/mm3 Precautions: Breastfeeding, children, females, geriatric patients, cardiovascular/ hepatic/renal disease, CNS disorder, bone marrow suppression, dental disease, dental work, extravasation, herpes, infection, infertility, jaundice, ocular exposure, radiation therapy, thrombocytopenia, vaccination
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Black Box Warning: Anaphylaxis, bone marrow suppression, requires a special- ized care setting, requires an experienced clinician Black Box Warning: Confirmation that dexamethasone was given 12 hr and 6 hr before infusion begins • Store prepared sol up to 27 hr in re- frigerator Intermittent IV INFUSION route Black Box Warning: After premedicating with dexamethasone 20 mg PO 12 hr and 6 hr before PACLitaxel, diphenhydrAMINE 50 mg IV 1/2-1 hr before PACLitaxel and cimetidine 300 mg or ranitidine 50 mg IV 1/2-1 hr before PACLitaxel • Assess for extravasation if given by regular IV, not port PACLitaxel Continuous IV INFUSION • Dilute 30 mg vial/5 mL • After diluting in 0.9% NaCl, D5W, D5 and 0.9% NaCl, D5LR (0.3-1.2 mg/mL), chemo dispensing pin or similar devices with spikes should not be used in vials of PACLitaxel; use in-line filter ≤0.22 micron; • Using only glass bottles, polypropyl- ene, polyolefin bags, and administration sets; do not use PVC infusion bags or sets PACLitaxel Protein Bound Par- ticles Intermittent IV INFUSION route • No premedication for allergic reaction is needed • Reconstitute vial by injecting 20 mL of 0.9% NaCl; slowly inject 20 mL of 0.9% NaCl over at least 1 min to direct sol flow on wall of vial (5 mg/mL); do not inject 0.9% NaCl directly onto lyophilized cake (foaming will occur); allow vial to sit for at least 15 min to ensure proper wetting of lyophilized cake; gently swirl or invert vial slowly for ≥2 min until completely dissolved, should look milky • Calculate dose by dosing vol/mL = to- tal dose (mg) ÷ 5 (mg/mL) • Use PVC IV bag, do not use filter • Solution is stable for 8 hr refrigerated • Give over 30 min, monitor for extrava- sation and hypersensitivity • Do not admix Black Box Warning: Requires a special- ized care setting such as a hospital or fa- cility with management of complications; should be used by a clinician experienced in cytotoxic agents Black Box Warning: Bone marrow suppression: CBC, differential, platelet count before treatment and weekly; with- hold product if WBC is <1500/mm3 or platelet count is <100,000/mm3; notify prescriber • Cardiovascular status: ECG continu- ously in CV conditions; monitor for hypo- tension, sinus bradycardia/tachycardia • Peripheral neuropathy: paresthesias, numbness; during infusion, use ice packs on extremities to lessen continued neurop- athy; may use acupuncture for some relief; use of ice on extremities when infusing • Arthralgia, myalgia: may begin 2-3 days after infusion and continue for 4-5 days; may use analgesics • Nausea, vomiting: premedicate with an- tiemetics; nausea and vomiting occur often • PACLitaxel: CBC and differential base- line and periodically, leukocytes <1500/ mm, platelets 100,000/mm3 hold, nadir is 11 days (leukopenia) recovery 15-21 days • PACLitaxel Protein Bound Particles: CBC and differential on days 1, 8, 15, hold if neutrophils <1500/mm3 × 1 wk, reduce all doses • Hepatic studies before, during therapy (bilirubin, AST, ALT, LDH) prn or monthly, check for jaundiced skin and sclera, dark urine, clay-colored stool, itchy skin, ab- dominal pain, fever, diarrhea • VS during 1st hr of infusion, check IV site for signs of infiltration Black Box Warning: Hypersensitivity reactions, anaphylaxis: hypotension, dyspnea, angioedema, generalized ur- ticaria Stevens-Johnson syndrome; discontinue infusion immediately; keep emergency equipment available, monitor continuously during first 30-60 min, then periodically, usually occurs in first few minutes, pretreat with dexamethasone, diphenhydramine • Flushing: for mild to moderate flush, may continue diphenhydrAMINE for ≤48 hr • Effects of alopecia on body image; discuss feelings about body changes • Pregnancy/breastfeeding: do not use in pregnancy, breastfeeding
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SIDE EFFECTS CNS: Peripheral neuropathy, dizziness, headache, seizures CV: Bradycardia, hypotension, abnormal ECG, supraventricular tachycardia (SVT) GI: Nausea, vomiting, diarrhea, muco sitis, stomatitis, pancreatitis HEMA: Neutropenia, leukopenia, throm- bocytopenia, anemia INTEG: Alopecia, tissue necrosis, gener- alized urticaria, flushing MS: Arthralgia, myalgia RESP: Pulmonary embolism, dyspnea, cough SYST: Hypersensitivity reactions, ana- phylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema GU: Renal failure
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INTERACTIONS Increase: myelosuppression—other anti- neoplastics, radiation Increase: DOXOrubicin levels—DOXO- rubicin P Increase: bleeding risk—NSAIDs, antico- agulants, platelet inhibitors, thrombolytics Decrease: PACLitaxel levels-CYP2C8, CYP 2C9 inducers: phenobarbitol, phenytoin Decrease: PACLitaxel metabolism—vera- pampil, cyclosporine, diazePAM, tenipo- side, etoposide, quinidine, vinecristine, testosterone, ketoconazole, estradiol Decrease: immune response—live virus vaccines Drug/Lab Test Increase: AST/ALT, alk phos, triglycerides Decrease: neutrophils, platelets, WBC, HB
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DOSAGE AND ROUTES PACLitaxel Ovarian carcinoma • Adult: IV INFUSION 135 mg/m2 given over 24 hr or 175 mg/m2 over 3 hr q3wk, then CISplatin 75 mg/m2 Breast carcinoma node positive • Adult: IV INFUSION 175 mg/m2 over 3 hr q3wk × 4 courses AIDS-related Kaposi’s sarcoma • Adult: IV INFUSION 135 mg/m2 over 3 hr q3wk or 100 mg/m2 over 3 hr q2wk First-line non–small-cell lung cancer • Adult: IV INFUSION 135 mg/m2/24 hr infusion with CISplatin 75 mg/m2 × 3 wk Hepatic dose • Adult: Dose reduction for 135 mg/m2 24-hr IV INFUSION—AST/ALT 2-10 × ULN, total bilirubin ≤1.5 mg/dL: give 100 mg/m2; AST/ALT <10 × ULN, total bilirubin 1.6-7.5 mg/dL: 50 mg/m2; AST/ALT ≥10 × ULN or total bilirubin >7.5 mg/dL: avoid use • Adult: Dose reduction for 175 mg/m2 3-hr IV INFUSION—AST/ALT <10 × ULN, total bilirubin 1.26-2 × ULN: give 135 mg/ m2; AST/ALT <10 × ULN, total bilirubin 2.01-5 × ULN: 90 mg/m2; AST/ALT ≥10 × ULN or total bilirubin >5 × ULN: avoid use PACLitaxel protein-bound particles Metastatic pancreatic cancer • Adult: IV infusion 125 mg/m2 over 30-40 min on days 1, 8, 15 of each 28- day cycle followed by gemcitabine 1000 mg/m2 IV over 30-40 min, on days 1, 8, 15, and 28
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Available forms: Inj 6 mg/5mL, pow- der for inj, lyophilized 100 mg in single- use vials (Abraxane)
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Administer: • If CISplatin is given, use after taxane • Use cytotoxic handling procedures
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Assess:
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Evaluate: • Therapeutic response: decreased tu- mor size, spread of malignancy
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To report signs of infection: fever, sore throat, flulike symptoms • To report signs of anemia: fatigue, headache, faintness, SOB, irritability • To report bleeding; to avoid use of ra- zors, commercial mouthwash; to use soft-bristle toothbrush; to use viscous xylocaine or compounded formula for stomatitis • To avoid use of aspirin, ibuprofen • To avoid crowds, persons with known infections • That hair may be lost during treatment; that a wig or hairpiece may make patient feel better; that new hair may be different in color, texture • That pain in muscles and joints 2-5 days after infusion is common • To notify prescriber if pregnancy is planned or suspected; do not breast- feed • To avoid receiving vaccinations while taking product HIGH ALERT
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PHARMACOKINETICS 89%-98% of product serum protein bound, metabolized in liver, excreted in bile and urine; terminal half-life 5.3-17.4 hr
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• Adult: IV INFUSION 135 mg/m2 given over 24 hr or 175 mg/m2 over 3 hr q3wk, then CISplatin 75 mg/m2 Breast carcinoma node positive
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• Adult: IV INFUSION 175 mg/m2 over 3 hr q3wk × 4 courses AIDS-related Kaposi’s sarcoma
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• Adult: IV INFUSION 135 mg/m2 over 3 hr q3wk or 100 mg/m2 over 3 hr q2wk First-line non–small-cell lung cancer
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• Adult: IV INFUSION 135 mg/m2/24 hr infusion with CISplatin 75 mg/m2 × 3 wk Hepatic dose
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• Adult: Dose reduction for 135 mg/m2 24-hr IV INFUSION—AST/ALT 2-10 × ULN, total bilirubin ≤1.5 mg/dL: give 100 mg/m2; AST/ALT <10 × ULN, total bilirubin 1.6-7.5 mg/dL: 50 mg/m2; AST/ALT ≥10 × ULN or total bilirubin >7.5 mg/dL: avoid use
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• Adult: Dose reduction for 175 mg/m2 3-hr IV INFUSION—AST/ALT <10 × ULN, total bilirubin 1.26-2 × ULN: give 135 mg/ m2; AST/ALT <10 × ULN, total bilirubin 2.01-5 × ULN: 90 mg/m2; AST/ALT ≥10 × ULN or total bilirubin >5 × ULN: avoid use PACLitaxel protein-bound particles Metastatic pancreatic cancer
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• Adult: IV infusion 125 mg/m2 over 30-40 min on days 1, 8, 15 of each 28- day cycle followed by gemcitabine 1000 mg/m2 IV over 30-40 min, on days 1, 8, 15, and 28
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