PACLITAXEL ■ PACLITAXEL PROTEIN-BOUND PARTICLES FOR INJECTABLE SUSPENSION (ALBUMIN-BOUND) 
Pronounciation
- (PACK-lih-tax-el)
Trade Name(s)
- Onxol, Taxol
Abraxane
PACLITAXEL ■ PACLITAXEL PROTEIN-BOUND PARTICLES FOR INJECTABLE SUSPENSION (ALBUMIN-BOUND)
Pronounciation
Trade Name(s)
Verify pregnancy status. Baseline studies required; see Monitor and Dose Adjustments.
Several regimens of paclitaxel, alone or in combination with other antineoplastics, are in use. Doses vary, depending on the regimen used. Consult literature. ■ For all uses, premedication, specific parameters, and specific equipment are required before or during administration; see Premedication, Dose Adjustments, and Precautions/Monitor.
Must be premedicated before each dose to prevent severe hypersensitivity reactions. Usual regimen includes oral dexamethasone 20 mg 12 and 6 hours before; IV diphenhydramine 50 mg 30 to 60 minutes before; and an H2antagonist (e.g., famotidine 20 mg) 30 to 60 minutes before dosing with paclitaxel. When premedicating patients with AIDS-related Kaposi’s sarcoma, reduce the dose of dexamethasone to 10 mg at 12 and 6 hours before paclitaxel. The doses of IV diphenhydramine and IV H2antagonists remain as above.
Ovarian cancer in previously untreated patients:
135 mg/M2 as an infusion over 24 hours. Follow with cisplatin 75 mg/M2 as an infusion over 6 to 8 hours. Repeat every 3 weeks. An alternative regimen is paclitaxel 175 mg/M2 as an infusion over 3 hours. Follow with cisplatin 75 mg/M2 (one source suggests an infusion over 24 hours; another suggests 6 to 8 hours, which would allow for outpatient therapy). Repeat every 3 weeks. See comments under Usual Dose.
Ovarian cancer in patients previously treated with chemotherapy:
135 or 175 mg/M2 as an infusion over 3 hours. An alternate regimen suggests the same dose given as a 24-hour infusion. Repeat every 3 weeks. Larger doses, with or without filgrastim (G-CSF, Neupogen), have produced similar responses. See comments under Usual Dose.
Adjuvant treatment of node-positive breast cancer:
175 mg/M2 as an infusion over 3 hours. Repeat every 3 weeks for four courses. Administered sequentially to doxorubicin-containing combination therapy. Clinical trials used four courses of doxorubicin and cyclophosphamide. Administer filgrastim (G-CSF) 5 mcg/kg/dose on Days 3 through 10. See comments under Usual Dose.
Breast cancer in patients previously treated with chemotherapy:
175 mg/M2 as an infusion over 3 hours. Repeat every 3 weeks. An alternate regimen suggests 175 to 250 mg/M2 over 3 hours every 3 weeks. See comments under Usual Dose.
First-line treatment of non–small-cell lung cancer:
135 mg/M2 as an infusion over 24 hours. Follow with cisplatin 75 mg/M2 over 6 to 8 hours. Repeat every 3 weeks. See comments under Usual Dose. A Canadian source recommends 175 mg/M2 as an infusion over 3 hours followed with cisplatin 75 mg/M2 over 6 to 8 hours and repeated every 3 weeks.
AIDS-related Kaposi’s sarcoma:
135 mg/M2 as an infusion over 3 hours. An alternate regimen suggests the same dose given as a 24-hour infusion. Repeat every 3 weeks. Another regimen is 100 mg/M2 as an infusion over 3 hours repeated every 2 weeks. Toxicity somewhat increased with 135 mg/M2 dose in clinical studies. See comments under Usual Dose.
Generally not required; see Precautions.
Metastatic breast cancer (MBC):
260 mg/M2 as an infusion over 30 minutes every 3 weeks.
Non–small-cell lung cancer (NSCLC):
100 mg/M2 as an infusion over 30 minutes on Days 1, 8, and 15 of each 21-day cycle. Given in combination with carboplatin on Day 1 only of each 21-day cycle, beginning immediately after the completion of Abraxane administration.
Adenocarcinoma of the pancreas:
125 mg/M2 as an infusion over 30 to 40 minutes followed by gemcitabine 1,000 mg/M2 as an infusion over 30 to 40 minutes on Days 1, 8, and 15 of each 28-day cycle.
Reduce dose by 20% for subsequent courses in patients who experience severe peripheral neuropathy or severe neutropenia (neutrophils less than 500 cells/mm3) for 1 week or longer. ■ Withhold therapy if neutrophils below 1,500/mm3 or platelets below 100,000/mm3. ■ Dose reduction not required in impaired renal function. ■ In AIDS-related Kaposi’s sarcoma the parameters are slightly different. Initiate or repeat paclitaxel only if neutrophil count is equal to or greater than 1,000/mm3; reduce dose of dexamethasone to 10 mg/dose; reduce dose of paclitaxel by 20% in patients who experience severe neutropenia (neutrophils less than 500/mm3 for a week or longer); use concomitant filgrastim (G-CSF) as clinically indicated. ■ Recommendations for dose adjustment of the initial course of therapy in patients with impaired hepatic function are listed in the following chart.
a These recommendations are based on clinical trials of dosages for patients without hepatic impairment of 135 mg/M2 over 24 hours or 175 mg/M2 over 3 hours; data are not available to make dose adjustment recommendations for other regimens (e.g., for AIDS-related Kaposi’s sarcoma). b Differences in criteria for bilirubin levels between the 3- and 24-hour infusion are due to differences in clinical trial design. c Dosage recommendations are for the first course of therapy; further dose reduction in subsequent courses should be based on individual tolerance. | |||||||||||||||||||||||||||||||||||||||||||||||||||
Adjustment of starting dose is not necessary in patients with mild to moderate renal impairment (CrCl equal to or greater than 30 to less than 90 mL/min). ■ Withhold therapy in all patients if neutrophils below 1,500/mm3.■ In patients with MBC, withhold therapy if platelets below 100,000/mm3. ■ For MBC, reduce dose to 220 mg/M2 in patients who experience severe neutropenia (neutrophils less than 500 cells/mm3 for 7 days or more) or severe sensory neuropathy. Further reduce dose to 180 mg/M2 for subsequent courses if severe neutropenia (less than 500 cells/mm3 for 7 days or more) or severe sensory neuropathy recurs. ■ If Grade 3 sensory neuropathy occurs, withhold treatment until resolution to Grade 1 or 2 for MBC or until resolution to less than or equal to Grade 1 for NSCLC, followed by a dose reduction for all subsequent courses. ■ No dose adjustment is necessary for patients with mild hepatic impairment (total bilirubin greater than the ULN and less than or equal to 1.5 times the ULN and AST less than or equal to 10 times the ULN), regardless of indication. ■ Do not administer Abraxane to patients with total bilirubin greater than 5 times the ULN or AST greater than 10 times the ULN regardless of indication because these patients have not been studied. ■ Do not administer Abraxane to patients with metastatic adenocarcinoma of the pancreas who have moderate to severe hepatic impairment. ■ Recommendations for a starting dose in patients with hepatic impairment are shown in the following chart. Doses for subsequent cycles should be based on patient tolerance.
a Dose recommendations are for the first course of therapy. The need for further dose adjustments in subsequent courses should be based on individual tolerance. b Patients with bilirubin levels above the ULN were excluded from clinical trials for pancreatic or lung cancer. c A dose increase to 260 mg/M2 for patients with MBC or to 100 mg/M2 for patients with NSCLC in subsequent courses should be considered if the patient tolerates the reduced dose for two cycles. | |||||||||||||||||||||||||||||||||||||||||||||
MBC, Metastatic breast cancer; N/R, not recommended; NSCLC, non–small-cell lung cancer.
■In patients with NSCLC who develop severe neutropenia or thrombocytopenia, withhold therapy until counts recover to an ANC of at least 1,500 cells/mm3 and platelets of at least 100,000 cells/mm3 on Day 1 or to an ANC of at least 500 cells/mm3 and platelets of at least 50,000 cells/mm3 on Day 8 or 15 of the cycle. Upon resumption of dosing, follow dose reduction outlined in the following chart.
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■Dose-level reductions for patients with adenocarcinoma of the pancreas are outlined in the following chart.
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■Dose modifications for neutropenia and/or thrombocytopenia for patients with adenocarcinoma of the pancreas are provided in the following chart.
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ANC, Absolute neutrophil count.
■Dose modifications for other adverse reactions for patients with adenocarcinoma of the pancreas are provided in the following chart.
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Specific techniques required; see Precautions.
Must be diluted and given as an infusion. May leach the toxic plasticizer DEHP from PVC infusion bags or sets; prepare and store in bottles (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administer through polyethylene-lined administration sets. Compatible with NS, D5W, D5NS, or D5R. Final concentration of 0.3 to 1.2 mg/mL required. For a 135 mg/M2 dose, a large adult (body surface about 2 M2) will receive 270 mg (45 mL of paclitaxel at 6 mg/mL). Will require dilution in an additional 180 mL to make a 1.2 mg/mL concentration or in an additional 855 mL to make a 0.3 mg/mL concentration. Solution may appear hazy. Do not use a chemo-dispensing pin; can cause the stopper to collapse and result in loss of sterility.
Available in single-use vials, each containing 100 mg (5 mg/mL after reconstitution with 20 mL of NS). Calculate the exact number of vials needed to achieve the total dosing volume of suspension required.
Total # of vials required = Total dose (mg) ÷ 100 mg
Dosing volume (mL) = Total dose (mg) ÷ 5 (mg/mL)
For example, a MBC patient with a body surface area (BSA) of 1.73 M2 would need a dose of 449.8 mg of Abraxane. 449.8 mg divided by 100 mg equals 4.498 vials, so 5 vials of Abraxane would be needed. 449.8 mg divided by 5 (mg/mL) equals a dosing volume of 90 mL of reconstituted solution.
Reconstitute each 100-mg vial with 20 mL of NS. A specific process is required to avoid foaming or clumping. Over a minimum of 1 minute, slowly inject the NS, directing it to the inside wall of the vial. Do not allow the NS to flow directly onto the lyophilized cake (will cause foaming). Allow each vial to sit for a minimum of 5 minutes while the NS wets the cake. Gently swirl and/or invert each vial slowly for at least 2 minutes until complete dissolution. Avoid generation of foam. If foaming or clumping occurs, allow solution to stand for at least 15 minutes until foam subsides. Solution should be milky and homogenous without visible particulates. If particulates are visible, gently invert to ensure complete resuspension before use.
Withdraw the calculated volume and inject into an empty sterile polyvinyl chloride (PVC) container or a PVC or non–PVC-type infusion bag (a total dosing volume of 90 mL in the previous example). The use of medical devices containing silicone oil as a lubricant (i.e., syringes and IV bags) to reconstitute and administer Abraxane may result in the formation of proteinaceous strands. Discard suspension if proteinaceous strands, particulate matter, or discoloration are observed.
Use of an in-line filter not greater than 0.22 microns required for administration.
Conventional paclitaxel: May be stored at CRT or refrigerated before dilution (may appear precipitated under refrigeration; will redissolve at room temperature). Diluted for infusion, it is stable at room temperature for up to 27 hours. Abraxane: Store vials in original package at 20° to 25° C (68° to 77° F). Protect from light. Refrigeration or freezing does not affect stability of the product. Immediate use of reconstituted solution is preferred, but reconstituted vial may be refrigerated at 2° to 8° C (36° to 46° F) for a maximum of 24 hours if necessary. If refrigeration required, return to original carton to protect from light. Ensure complete resuspension after removing from refrigerator by gently inverting. Discard unused portions of the vial. Reconstituted solution in an infusion bag should be used immediately; however, it may be refrigerated and protected from bright light for a maximum of 24 hours. The total combined refrigerated storage time of reconstituted Abraxane in the vial and in the infusion bag is 24 hours. This may be followed by storage in the infusion bag at ambient temperature and lighting conditions for a maximum of 4 hours.
Leaches out plasticizers; see Dilution.
Other sources suggest specific compatibilities dependent on concentration and manufacturer; consult a pharmacist.
Manufacturer states, “Use of specialized DEHP-free solution containers or administration sets is not necessary.” The use of medical devices containing silicone oil as a lubricant (i.e., syringes and IV bags) to reconstitute and administer Abraxane may result in the formation of proteinaceous strands. Additional specific information not available.
A single dose properly diluted must be equally distributed over 3 hours or as indicated in Usual Dose. Use of an in-line filter not greater than 0.22 microns required. Use a metriset (60 gtt/mL) or an infusion pump appropriate to control flow. Rate extended to 24 hours in some regimens.
A single dose properly reconstituted and equally distributed over 30 minutes.
An antineoplastic. A novel antimicrotubule inhibitor. Paclitaxel derived from the bark of Pacific yew has now been replaced by paclitaxel produced semi-synthetically from a renewable source (needles and twigs of the Himalayan yew). Both are chemically identical. Through specific processes it stabilizes microtubules by preventing depolymerization. This action inhibits the normal dynamic reorganization of the microtubule network essential for vital interphase and mitotic cellular functions. Also induces abnormal bundles of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis. Distribution and/or tissue binding is extensive. Evidence suggests metabolism in the liver via the cytochrome P450 isoenzyme system (CYP2C8 and CYP3A4). Terminal half-life ranges from 13.1 to 27 hours. Excreted primarily as metabolites in feces and, to a lesser extent, in urine.
More active in patients who have not received previous chemotherapy.
Consists of albumin-bound paclitaxel nanoparticles. Highly bound to serum proteins; metabolized in the liver, primarily by CYP2C8 and, to a lesser extent, by CYP3A4. Terminal half-life ranges from 13 to 27 hours. Minimal excretion in urine and feces.
First-line and subsequent therapy for the treatment of advanced carcinoma of the ovary. ■ First-line treatment for ovarian cancer in combination with cisplatin. ■ Adjuvant treatment of node-positive breast cancer administered sequentially to standard doxorubicin-containing combination chemotherapy. Most effective in estrogen- and progesterone-receptor–negative tumors. ■ Metastatic breast cancer refractory to initial chemotherapy or for a relapse within 6 months. ■ First-line treatment, in combination with cisplatin, for non–small-cell lung cancer in patients who are not candidates for potentially curative surgery or radiation therapy. ■ Second-line treatment of AIDS-related Kaposi’s sarcoma.
Treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated. ■ First-line treatment of locally advanced or metastatic non–small-cell lung cancer (NSCLC) (in combination with carboplatin) in patients who are not candidates for curative surgery or radiation therapy. ■ First-line treatment of patients with metastatic adenocarcinoma of the pancreas, in combination with gemcitabine.
Conventional paclitaxel: Advanced head and neck cancer. ■ Cancers of the bladder and cervix. ■ Small-cell lung cancer. ■ In combination with other agents for treatment of metastatic breast cancer. ■ Relapsed or refractory testicular cancer and testicular germ cell tumors. ■ Treatment of (unknown primary) adenocarcinoma. Abraxane: Recurrent ovarian, fallopian, and primary peritoneal cancers.
Baseline neutropenia less than 1,500 cells/mm3in patients with solid tumors or baseline neutropenia less than 1,000 cells/mm3in patients with AIDS-related Kaposi’s sarcoma. History of prior severe hypersensitivity reactions to paclitaxel or other drugs formulated in polyoxyethylated castor oil (Cremophor EL [e.g., cyclosporine, teniposide]).
Baseline neutrophil count less than 1,500 cells/mm3.■ Patients who experience a severe hypersensitivity reaction to Abraxane should not be rechallenged with the drug.
Follow guidelines for handling cytotoxic agents. See Appendix A. ■ Usually administered by or under the direction of the physician specialist in a facility with adequate diagnostic and treatment facilities to monitor the patient and respond to any medical emergency.
Use caution in patients with cardiac conduction abnormalities, CHF, and MI within previous 6 months. ■ Bradycardia, hypertension, and hypotension have been observed but rarely required treatment. Occasionally the infusion must be interrupted or discontinued because of initial or recurrent hypertension; see Monitor. ■ Pre-existing neuropathies resulting from prior therapies are not a contraindication for paclitaxel therapy. ■ Various studies show that incidence and severity of neurotoxicity and hematologic toxicity increase with dose, especially above 190 mg/M2. ■ Use with caution in patients with a total bilirubin greater than 2 times the ULN. May be at increased risk of toxicity, especially profound myelosuppression; see Dose Adjustments. ■ See Drug/Lab Interactions.
Do not substitute for or with other paclitaxel formulations.■ Use of gloves recommended. Wash skin immediately if contact occurs. Flush mucous membranes thoroughly with water if contact occurs. Topical exposure may result in tingling, burning, and redness. ■ Premedication to prevent hypersensitivity reactions is not required but may be needed in patients who have had a prior hypersensitivity reaction to Abraxane. Reports of severe and sometimes fatal hypersensitivity reactions have occurred; see Contraindications; do not rechallenge patients who have had a severe reaction. ■ Neutropenia is dose dependent and is a dose-limiting toxicity. Do not administer Abraxane to patients with a baseline absolute neutrophil count (ANC) of less than 1,500 cells/mm3; see Dose Adjustments. ■ Sensory neuropathy is dose dependent and schedule dependent and occurs frequently; see Dose Adjustments. ■ Sepsis occurred in 5% of patients, with or without neutropenia, who received Abraxane in combination with gemcitabine. Biliary obstruction or the presence of a biliary stent were risk factors for severe or fatal sepsis. ■ Pneumonitis, including some cases that were fatal, has been reported in patients receiving Abraxane in combination with gemcitabine; see Antidote. ■ Has not been studied in patients with severe renal dysfunction or end-stage renal disease. ■ Use with caution in patients with hepatic impairment. May be at increased risk for toxicity, particularly myelosuppression; see Dose Adjustments. ■ Derived from human albumin; may carry a risk of transmission of viral disease or Creutzfeldt-Jakob disease; risk considered extremely remote. ■ Has not been studied in patients who have had a hypersensitivity reaction to conventional paclitaxel.
Neutropenia is dose dependent and is the dose-limiting toxicity. Obtain baseline CBC with differential and platelet count. Monitor frequently during therapy and before each dose.■ Monitor injection site carefully; avoid extravasation. ■ Observe closely for signs of infection. Prophylactic antibiotics may be indicated pending results of C/S in a febrile neutropenic patient. ■ Use prophylactic antiemetics to reduce nausea and vomiting and increase patient comfort. ■ Monitor for thrombocytopenia (platelet count less than 50,000/mm3). Initiate precautions to prevent excessive bleeding (e.g., inspect IV sites, skin, and mucous membranes; use extreme care during invasive procedures; test urine, emesis, stool, and secretions for occult blood).
Neutrophil nadir occurs around Day 11; see Dose Adjustments. ■ Monitor VS frequently, particularly during the first hour of the infusion. ■ Consider obtaining a baseline ECG; arrhythmias have occurred. Continuous cardiac monitoring required for all patients with an abnormal baseline ECG or for those who experienced conduction arrhythmias during administration of a previous dose. ■ Monitoring of cardiac function is recommended when paclitaxel is used in combination with doxorubicin; see doxorubicin monograph. ■ Anaphylaxis and severe hypersensitivity reactions characterized by dyspnea, hypotension requiring treatment, angioedema, and generalized urticaria have been reported. Fatal reactions have occurred despite premedication.■ Most severe hypersensitivity reactions occur in the first hour; chest pain, dyspnea, flushing, and tachycardia were the most frequent initial symptoms; abdominal pain, diaphoresis, extremity pain, and hypertension also occurred. Monitor all vital signs, including BP, continuously for the first 30 minutes of the infusion and at frequent intervals after that. Incidence seems to decrease with subsequent doses. ■ Treatment can often be continued in patients with mild hypersensitivity reactions if proper premedication is given. ■ Monitor injection site carefully; avoid extravasation. Incidence of inflammation increased with 24-hour infusions. Injection site reactions may occur during administration or be delayed by 7 to 10 days. Recurrence of skin reactions at a site of previous extravasation following administration of paclitaxel (“recall”) has been reported.
Limited infusion time (30 minutes) reduces the likelihood of infusion-related reactions; however, they have been reported; monitor for S/S. ■ Monitor for S/S of hypersensitivity reactions. ■ Monitor for S/S of sensory neuropathy. ■ Monitor for S/S of pneumonitis. ■ Based on patient history, a baseline ECG may be indicated. ■ See Precautions and Dose Adjustments.
Effective birth control recommended for males and females; see Maternal/Child. ■ Review of monitoring requirements and adverse events before therapy imperative. ■ Report any unusual or unexpected symptoms, side effects, pain or burning at injection site, S/S of a hypersensitivity reaction (e.g., bronchospasm, difficulty breathing, rash, urticaria), signs of infection (e.g., chills, fever, night sweats), signs of sensory neuropathy (e.g., numbness, tingling, or burning in hands and/or feet), signs of pneumonitis (e.g., dry, persistent cough or shortness of breath), or signs of bleeding (e.g., bruising, tarry stools, blood in urine, pinpoint red spots on skin) as soon as possible. ■ Avoid tasks that require mental alertness (e.g., driving, operating machinery) until the effect of the medication is known. Side effects such as fatigue, lethargy, and malaise may affect the ability to perform these tasks. ■ See Appendix D. ■ Obtain name and telephone number of a contact person for emergencies, questions, or problems. ■ Seek resources for counseling or supportive therapy. ■ Manufacturer provides a patient information booklet.
Category D: females should avoid pregnancy, and males should avoid fathering a child. May cause fetal harm. ■ Discontinue breast-feeding. ■ Safety and effectiveness for use in pediatric patients not established.
CNS toxicity (rarely associated with death) was reported in one pediatric trial using high-dose paclitaxel. Use of antihistamines and the ethanol contained in the paclitaxel may have contributed to toxicity noted.
Studies suggest response is similar to that seen in younger patients.
Incidence of side effects, including myelosuppression, neuropathy, and cardiovascular events, may be increased in the elderly.
Increased incidence of dehydration, diarrhea, epistaxis, fatigue, and peripheral edema was seen in elderly patients receiving Abraxane as monotherapy for MBC. Incidence of myelosuppression, neuropathy, and arthralgia was more common in patients receiving Abraxane and carboplatin for treatment of NSCLC. Incidence of decreased appetite, dehydration, diarrhea, and epistaxis was more common in patients receiving Abraxane and gemcitabine for treatment of adenocarcinoma of the pancreas.
Do not administer chloroquine or live virus vaccines to patients receiving antineoplastic agents.
Formal drug interaction studies have not been conducted. To reduce potential for profound myelosuppression when using paclitaxel and cisplatin concurrently, give paclitaxel first, then cisplatin. ■ Neurotoxicity and symptomatic motor dysfunction occurring with higher doses (greater than 250 mg/M2) may be potentiated by cisplatin and filgrastim (G-CSF). ■ May cause additive effects with bone marrow–suppressing agents, radiation therapy, or agents that cause blood dyscrasias (e.g., amphotericin B, antithyroid agents [methimazole], azathioprine, chloramphenicol, ganciclovir, interferon, plicamycin, zidovudine). Reduced doses may be required. ■ May increase levels of doxorubicin and its active metabolite when drugs are used in combination. ■ Metabolized by cytochrome P450 isoenzymes CYP3A4 and CYP2C8. Use caution when administered concomitantly with known substrates (e.g., buspirone, eletriptan, felodipine, lovastatin, midazolam, sildenafil, simvastatin, and triazolam), inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir), and inducers (e.g., rifampin and carbamazepine) of CYP3A4.■ Other medications that are substrates and/or inducers of CYP3A4 may alter the metabolism of paclitaxel but have not been evaluated in clinical trials. ■ Use caution when administered concomitantly with known substrates (e.g., repaglinide), inhibitors (e.g., gemfibrozil), and inducers (e.g., rifampin) of CYP2C8.
Drug interaction studies have not been conducted. See All Formulations above. ■ Use caution when administering with medicines known to inhibit or induce CYP2C8 or CYP3A4. Drugs that may inhibit these enzymes include ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir, and nelfinavir. Drugs that may induce these enzymes include rifampin, carbamazepine, phenobarbital, phenytoin, efavirenz, and nevirapine.
Dose dependent and generally reversible, but may be fatal. All patients were premedicated to prevent hypersensitivity reactions. Abnormal ECG, alopecia, arthralgia/myalgia, asthenia, autonomic neuropathy resulting in paralytic ileus, bleeding, bone marrow suppression (anemia, leukopenia, neutropenia, thrombocytopenia), bradycardia, CHF (including cardiac dysfunction and reduction in left ventricular ejection fraction or ventricular failure [more common in patients receiving combination therapy with anthracyclines]), diarrhea, elevated alkaline phosphatase, elevated AST, elevated bilirubin, febrile neutropenia, fever, fluid retention and edema, hypersensitivity reactions (moderate [e.g., dyspnea, flushing, hypotension, rash, tachycardia]; severe [e.g., chest pain, dyspnea requiring bronchodilators, hypotension requiring treatment, generalized urticaria]), hypertension, hypotension, infections including opportunistic infections (chills, fever, night sweats), injection site reactions (cellulitis, fibrosis, induration, necrosis, phlebitis, skin exfoliation), mucositis, nausea and vomiting, numbness, optic nerve and/or visual disturbances, peripheral neuropathy, respiratory reactions (interstitial pneumonia, lung fibrosis, pleural effusions, pulmonary embolism, respiratory failure), Stevens-Johnson syndrome, toxic epidermal necrolysis, and visual disturbances. A grand mal seizure occurred in one patient. Other side effects (e.g., cardiac arrest, cardiac ischemia/infarction, CVA, hepatic necrosis, and hepatic encephalopathy leading to death; intestinal obstruction; intestinal perforation; ischemic colitis; pancreatitis; thrombosis/embolism) have been reported rarely. A higher incidence of elevated liver function tests and renal toxicity is seen in Kaposi’s sarcoma patients.
Diffuse edema, thickening, and sclerosing of the skin; exacerbation of S/S of scleroderma; ototoxicity.
Single-agent use in patients with MBC:
Abnormal ECG, alopecia, anemia, diarrhea, elevation of alkaline phosphate and AST, fatigue/asthenia, infections (oral candidiasis, pneumonia, and respiratory tract), myalgia/arthralgia, nausea, neutropenia, and sensory neuropathy are most common.
Combination use in patients with NSCLC:
Alopecia, anemia, fatigue, nausea, neutropenia, peripheral neuropathy, and thrombocytopenia are most common. The most serious side effects reported are anemia and pneumonia. The most common side effects that result in dose reduction, the withholding of a dose, or a delay in dosing are anemia, neutropenia, and thrombocytopenia. Neutropenia, peripheral neuropathy, and thrombocytopenia sometimes resulted in permanent discontinuation of Abraxane.
Combination use in patients with adenocarcinoma of the pancreas:
Alopecia, decreased appetite, dehydration, diarrhea, fatigue, fever, nausea, neutropenia, peripheral edema, peripheral neuropathy, rash, and vomiting. The most common serious side effects are dehydration, fever, pneumonia, and vomiting. The most common side effects that result in dose reduction or delay in dosing are anemia, diarrhea, fatigue, neutropenia, peripheral neuropathy, and thrombocytopenia. The most common side effects resulting in permanent discontinuation are fatigue, peripheral neuropathy, and thrombocytopenia.
Hypersensitivity reactions have occurred but are not usually severe; premedication is not indicated. Other side effects have been reported and include bradycardia, cardiovascular events (e.g., cardiac ischemia/infarction, SVT), dehydration, extravasation, fever, hypotension, pancytopenia, pneumonitis, pneumothorax, Stevens-Johnson syndrome, toxic epidermal necrolysis, and many others. Frequency of sensory neuropathy may increase with cumulative dose.
Many of these side effects occur with paclitaxel and Abraxane and include CHF, left ventricular dysfunction, and atrioventricular block; cranial nerve palsies; hepatic necrosis and hepatic encephalopathy; injection site reactions; interstitial pneumonia; intestinal obstruction or perforation; ischemic colitis; pancreatitis; paralytic ileus; pneumonitis; pulmonary embolism; visual disorders (reduced visual acuity); vocal cord paresis. Rare reports of severe hypersensitivity reactions have occurred with Abraxane.
Keep physician informed of all side effects. Most will be treated symptomatically as indicated. Most hypersensitivity reactions will subside with temporary discontinuation of paclitaxel, and incidence seems to decrease with subsequent doses. Moderate reactions such as dyspnea, flushing, hypotension, skin reactions, or tachycardia do not usually require interruption of treatment. Severe reactions may require epinephrine, antihistamines (e.g., diphenhydramine), corticosteroids (e.g., dexamethasone), or bronchodilators (e.g., albuterol, theophylline). Most severe reactions should not be rechallenged, but some patients tolerated subsequent doses of conventional paclitaxel; see Contraindications. Neutropenia can be profound, and the nadir usually occurs about Day 11 with conventional paclitaxel. Recovery is generally rapid and spontaneous but may be treated with filgrastim or pegfilgrastim. Severe thrombocytopenia (nadir Day 8 or 9 with conventional paclitaxel) may require platelet transfusions. Severe anemia (less than 8 Gm/dL) may require packed cell transfusions. Hypotension and bradycardia do not usually occur at the same time except in hypersensitivity. Treat only if symptomatic. Some arrhythmias (e.g., nonspecific repolarization abnormalities, sinus tachycardia, and PVCs) are common and may not require intervention. Promptly treat any serious or symptomatic arrhythmia (e.g., conduction abnormalities, ventricular tachycardia), and monitor continuously during subsequent doses. Neurologic symptoms tend to worsen with each course; see Dose Adjustments. Usually improve within several months. Severe peripheral neuropathies or seizure may necessitate discontinuation of paclitaxel. Permanently discontinue treatment with Abraxane and gemcitabine if pneumonitis develops. There is no specific antidote for overdose. Supportive therapy will help sustain the patient in toxicity. Resuscitate if indicated.