Abraxane

Paclitaxel protein-bound is a cancer medicine that interferes with the growth and spread of cancer cells in the body.

Paclitaxel protein-bound is used in the treatment of breast cancer, lung cancer, and pancreatic cancer.

Paclitaxel protein-bound is sometimes given with other cancer medicines.

Paclitaxel protein-bound may also be used for purposes not listed in this medication guide.

Paclitaxel protein-bound can be harmful if it gets in your eyes, mouth, or nose, or on your skin. If skin contact occurs, wash the area with soap and water or rinse the eyes thoroughly with plain water.

This medicine can pass into body fluids (urine, feces, vomit). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces. Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

• Black, tarry stools
• bloating or swelling of the face, arms, hands, lower legs, or feet
• blurred or double vision
• chest pain
• chills
• cough
• fever
• loss of taste
• lower back or side pain
• painful or difficult urination
• pale skin
• rapid weight gain
• sneezing
• sore mouth, tongue, or throat
• tightness in the chest
• tingling of the hands or feet
• troubled breathing with exertion
• ulcers, sores, or white spots in the mouth
• unusual bleeding or bruising
• unusual weight gain or loss
• unusual tiredness or weakness

• Anxiety
• bleeding
• blood in the urine or stools
• burning, tingling, numbness or pain in the hands, arms, feet, or legs
• confusion
• difficulty with swallowing
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fast, pounding, slow, or irregular heartbeat or pulse
• general feeling of discomfort or illness
• inability to move the arms, legs, or facial muscles
• inability to speak
• pain in the chest, groin, or legs, especially the calves
• pinpoint red spots on the skin
• rapid, shallow breathing
• sensation of pins and needles
• severe, sudden headache
• skin itching, rash, or redness
• slurred or slow speech
• stabbing pain
• sudden loss of coordination
• sudden, severe weakness or numbness in the arms or legs
• sudden, unexplained shortness of breath
• sweating
• swelling of the face, throat, or tongue
• thickening of bronchial secretions
• trouble thinking or walking

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Cracked lips
• decreased appetite
• diarrhea
• difficulty with moving
• headache
• lack or loss of strength
• loss of hair
• muscle pain or stiffness
• nausea
• pain in the joints
• swelling
• vomiting

• Bleeding, blistering, burning, coldness, discoloration of the skin, a feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site

• Nail changes

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.

Metastatic Breast Cancer

Abraxane is indicated for the 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.

Non-Small Cell Lung Cancer

Abraxane is indicated for the first-line treatment of locally advanced or metastatic non-small cell lung cancer, in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy.

Adenocarcinoma of the Pancreas

Abraxane is indicated for the first-line treatment of patients with metastatic adenocarcinoma of the pancreas, in combination with gemcitabine.

Pregnancy

Pregnancy Category D [see Warnings and Precautions (5.8)].

There are no adequate and well-controlled studies in pregnant women using Abraxane. Based on its mechanism of action and findings in animals, Abraxane can cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant while receiving Abraxane.

Administration of paclitaxel formulated as albumin-bound particles to rats during pregnancy, on gestation days 7 to 17 at doses of 6 mg/m2 (approximately 2% of the daily maximum recommended human dose on a mg/m2 basis) caused embryofetal toxicities, as indicated by intrauterine mortality, increased resorptions (up to 5-fold), reduced numbers of litters and live fetuses, reduction in fetal body weight and increase in fetal anomalies. Fetal anomalies included soft tissue and skeletal malformations, such as eye bulge, folded retina, microphthalmia, and dilation of brain ventricles. A lower incidence of soft tissue and skeletal malformations were also exhibited at 3 mg/m2 (approximately 1% of the daily maximum recommended human dose on a mg/m2 basis).

Nursing Mothers

It is not known whether paclitaxel is excreted in human milk. Paclitaxel and/or its metabolites were excreted into the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and effectiveness of Abraxane in pediatric patients have not been evaluated.

Geriatric Use

Of the 229 patients in the randomized study who received Abraxane for the treatment of metastatic breast cancer, 13% were at least 65 years of age and < 2% were 75 years or older. No toxicities occurred notably more frequently among patients who received Abraxane.

A subsequent pooled analysis was conducted in 981 patients receiving Abraxane monotherapy for metastatic breast cancer, of which 15% were 65 years of age or older and 2% were 75 years of age or older. A higher incidence of epistaxis, diarrhea, dehydration, fatigue and peripheral edema was found in patients 65 years of age or older.

Of the 514 patients in the randomized study who received Abraxane and carboplatin for the first-line treatment of non-small cell lung cancer, 31% were 65 years or older and 3.5% were 75 years or older. Myelosuppression, peripheral neuropathy, and arthralgia were more frequent in patients 65 years or older compared to patients younger than 65 years old. No overall difference in effectiveness, as measured by response rates, was observed between patients 65 years or older compared to patients younger than 65 years old.

Of the 431 patients in the randomized study who received Abraxane and gemcitabine for the first-line treatment of pancreatic adenocarcinoma, 41% were 65 years or older and 10% were 75 years or older. No overall differences in effectiveness were observed between patients who were 65 years of age or older and younger patients. Diarrhea, decreased appetite, dehydration and epistaxis were more frequent in patients 65 years or older compared with patients younger than 65 years old. Clinical studies of Abraxane did not include sufficient number of patients with pancreatic cancer who were 75 years and older to determine whether they respond differently from younger patients.

Patients with Hepatic Impairment

The exposure to paclitaxel may be higher in patients with hepatic impairment than in patients with normal hepatic function. Reduce Abraxane starting dose in patients with moderate to severe hepatic impairment. Do not administer Abraxane to patients with total bilirubin > 5 x ULN or AST > 10 x ULN [see Dosage and Administration (2.4), Warnings and Precautions (5.6) and Clinical Pharmacology (12.3)]. Do not administer to patients with metastatic adenocarcinoma of the pancreas who have moderate to severe hepatic impairment [see Dosage and Administration (2.4)].

Patients with Renal Impairment

Adjustment of the starting Abraxane dose is not required for patients with mild to moderate renal impairment (estimated creatinine clearance ≥30 to <90 mL/min) [see Clinical Pharmacology (12.3)]. There are insufficient data to permit dosage recommendations in patients with severe renal impairment or end stage renal disease (estimated creatinine clearance <30 mL/min).

Included as part of the PRECAUTIONS section.

Mechanism Of Action

ABRAXANE is a microtubule inhibitor that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. Paclitaxel induces abnormal arrays or “bundles” of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.

Pharmacokinetics

The pharmacokinetics of total paclitaxel following 30 and 180-minute infusions of ABRAXANE at dose levels of 80 to 375 mg/m² were determined in clinical studies. Dose levels of mg/m² refer to mg of paclitaxel in ABRAXANE. Following intravenous administration of ABRAXANE, paclitaxel plasma concentrations declined in a biphasic manner, the initial rapid decline representing distribution to the peripheral compartment and the slower second phase representing drug elimination.

The drug exposure (AUCs) was dose proportional over 80 to 300 mg/m² and the pharmacokinetics of paclitaxel for ABRAXANE were independent of the duration of intravenous administration.

The pharmacokinetic data of 260 mg/m² ABRAXANE administered over a 30-minute infusion was compared to the pharmacokinetics of 175 mg/m² paclitaxel injection over a 3-hour infusion. Clearance was larger (43%) and the volume of distribution was higher (53%) for ABRAXANE than for paclitaxel injection. There were no differences in terminal half-lives.

Following ABRAXANE administration to patients with solid tumors, paclitaxel is evenly distributed into blood cells and plasma and is highly bound to plasma proteins (94%). In a within-patient comparison study, the fraction of unbound paclitaxel in plasma was significantly higher with ABRAXANE (6.2%) than with solvent-based paclitaxel (2.3%). This contributes to significantly higher exposure to unbound paclitaxel with ABRAXANE compared with solvent-based paclitaxel, when the total exposure is comparable. In vitro studies of binding to human serum proteins, using paclitaxel concentrations ranging from 0.1 to 50 μg/mL, indicated that the presence of cimetidine, ranitidine, dexamethasone, or diphenhydramine did not affect protein binding of paclitaxel. The total volume of distribution is approximately 1741 L; the large volume of distribution indicates extensive extravascular distribution and/or tissue binding of paclitaxel.

In vitro studies with human liver microsomes and tissue slices showed that paclitaxel was metabolized primarily to 6α- hydroxypaclitaxel by CYP2C8; and to two minor metabolites, 3'-p-hydroxypaclitaxel and 6α, 3'-p-dihydroxypaclitaxel, by CYP3A4. In vitro, the metabolism of paclitaxel to 6α-hydroxypaclitaxel was inhibited by a number of agents (ketoconazole, verapamil, diazepam, quinidine, dexamethasone, cyclosporin, teniposide, etoposide, and vincristine), but the concentrations used exceeded those found in vivo following normal therapeutic doses. Testosterone, 17α-ethinyl estradiol, retinoic acid, and quercetin, a specific inhibitor of CYP2C8, also inhibited the formation of 6α-hydroxypaclitaxel in vitro. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with compounds that are substrates, inducers, or inhibitors of CYP2C8 and/or CYP3A4 [see DRUG INTERACTIONS].

At the clinical dose range of 80 to 300 mg/m², the mean total clearance of paclitaxel ranges from 13 to 30 L/h/m², and the mean terminal half-life ranges from 13 to 27 hours.

After a 30-minute infusion of 260 mg/m² doses of ABRAXANE, the mean values for cumulative urinary recovery of unchanged drug (4%) indicated extensive non-renal clearance. Less than 1% of the total administered dose was excreted in urine as the metabolites 6α-hydroxypaclitaxel and 3'-p-hydroxypaclitaxel.

Fecal excretion was approximately 20% of the total dose administered.

Specific Populations

The effect of hepatic impairment on the pharmacokinetics of paclitaxel following ABRAXANE administration was studied in patients with advanced solid tumors. The results showed that mild hepatic impairment (total bilirubin > 1 to ≤ 1.5 x ULN, AST ≤ 10 x ULN, n=8) had no clinically important effect on pharmacokinetics of paclitaxel. Patients with moderate (total bilirubin > 1.5 to ≤ 3 x ULN, AST ≤ 10 x ULN, n=7) or severe (total bilirubin > 3 to ≤ 5 x ULN, n=5) hepatic impairment had a 22% to 26% decrease in the maximum elimination rate of paclitaxel and approximately 20% increase in mean paclitaxel AUC compared with patients with normal hepatic function (total bilirubin ≤ ULN, AST ≤ ULN, n=130). [see DOSAGE AND ADMINISTRATION and Use In Specific Populations].

Elimination of paclitaxel shows an inverse correlation with total bilirubin and a positive correlation with serum albumin. Pharmacokinetic/pharmacodynamic modeling indicates that there is no correlation between hepatic function (as indicated by the baseline albumin or total bilirubin level) and neutropenia after adjusting for ABRAXANE exposure. Pharmacokinetic data are not available for patients with total bilirubin > 5 x ULN or for patients with metastatic adenocarcinoma of the pancreas [see DOSAGE AND ADMINISTRATION and Use in Specific Populations].

The effect of pre-existing mild (creatinine clearance ≥ 60 to < 90 mL/min, n=61) or moderate (creatinine clearance ≥ 30 to < 60 mL/min, n=23) renal impairment on the pharmacokinetics of paclitaxel following ABRAXANE administration was studied in patients with advanced solid tumors. Mild to moderate renal impairment had no clinically important effect on the maximum elimination rate and systemic exposure (AUC and Cmax) of paclitaxel [see Use In Specific Populations].

Population pharmacokinetic analyses for ABRAXANE show that body weight (40 to 143 kg), body surface area (1.3 to 2.4 m²), gender, race (Asian vs. White), age (24 to 85 years) and type of solid tumors do not have a clinically important effect on the maximum elimination rate and systemic exposure (AUC and Cmax) of paclitaxel.

Administration of carboplatin immediately after the completion of the ABRAXANE infusion to patients with NSCLC did not cause clinically meaningful changes in paclitaxel exposure. The observed mean AUCinf of free carboplatin was approximately 23% higher than the targeted value (6 min*mg/mL), but its mean half-life and clearance were consistent with those reported in the absence of paclitaxel.

Pharmacokinetic interactions between ABRAXANE and gemcitabine have not been studied in humans.

Clinical Studies

Metastatic Breast Cancer

Data from 106 patients accrued in two single arm open label studies and from 460 patients enrolled in a randomized comparative study were available to support the use of ABRAXANE in metastatic breast cancer.

In one study, ABRAXANE was administered as a 30-minute infusion at a dose of 175 mg/m² to 43 patients with metastatic breast cancer. The second trial utilized a dose of 300 mg/m² as a 30-minute infusion in 63 patients with metastatic breast cancer. Cycles were administered at 3-week intervals. Objective responses were observed in both studies.

This multicenter trial was conducted in 460 patients with metastatic breast cancer. Patients were randomized to receive ABRAXANE at a dose of 260 mg/m² given as a 30-minute infusion, or paclitaxel injection at 175 mg/m² given as a 3-hour infusion. Sixty-four percent of patients had impaired performance status (ECOG 1 or 2) at study entry; 79% had visceral metastases; and 76% had > 3 sites of metastases. Fourteen percent of the patients had not received prior chemotherapy; 27% had received chemotherapy in the adjuvant setting, 40% in the metastatic setting and 19% in both metastatic and adjuvant settings. Fifty-nine percent received study drug as second or greater than second-line therapy. Seventy-seven percent of the patients had been previously exposed to anthracyclines.

In this trial, patients in the ABRAXANE treatment arm had a statistically significantly higher reconciled target lesion response rate (the trial primary endpoint) of 21.5% (95% CI: 16.2% to 26.7%), compared to 11.1% (95% CI: 6.9% to 15.1%) for patients in the paclitaxel injection treatment arm. See Table 11. There was no statistically significant difference in overall survival between the two study arms.

Table 11: Efficacy Results from Randomized Metastatic Breast Cancer Trial

Non-Small Cell Lung Cancer

A multicenter, randomized, open-label study was conducted in 1052 chemonaive patients with Stage IIIb/IV non-small cell lung cancer to compare ABRAXANE in combination with carboplatin to paclitaxel injection in combination with carboplatin as first-line treatment in patients with advanced non-small cell lung cancer. ABRAXANE was administered as an intravenous infusion over 30 minutes at a dose of 100 mg/m² on Days 1, 8, and 15 of each 21-day cycle. Paclitaxel injection was administered as an intravenous infusion over 3 hours at a dose of 200 mg/m², following premedication. In both treatment arms carboplatin at a dose of AUC =6 mg•min/mL was administered intravenously on Day 1 of each 21-day cycle after completion of ABRAXANE/paclitaxel infusion. Treatment was administered until disease progression or development of an unacceptable toxicity. The major efficacy outcome measure was overall response rate as determined by a central independent review committee using RECIST guidelines (Version 1.0).

In the intent-to-treat (all-randomized) population, the median age was 60 years, 75% were men, 81% were White, 49% had adenocarcinoma, 43% had squamous cell lung cancer, 76% were ECOG PS 1, and 73% were current or former smokers. Patients received a median of 6 cycles of treatment in both study arms.

Patients in the ABRAXANE/carboplatin arm had a statistically significantly higher overall response rate compared to patients in the paclitaxel injection/carboplatin arm [(33% versus 25%) see Table 12]. There was no statistically significant difference in overall survival between the two study arms.

Table 12: Efficacy Results from Randomized Non-Small Cell Lung Cancer Trial (Intent-to-Treat Population)

Adenocarcinoma Of The Pancreas

A multicenter, multinational, randomized, open-label study was conducted in 861 patients comparing ABRAXANE plus gemcitabine versus gemcitabine monotherapy as first-line treatment of metastatic adenocarcinoma of the pancreas. Key eligibility criteria were Karnofsky Performance Status (KPS) ≥ 70, normal bilirubin level, transaminase levels ≤ 2.5 times the upper limit of normal (ULN) or ≤ 5 times the ULN for patients with liver metastasis, no prior cytotoxic chemotherapy in the adjuvant setting or for metastatic disease, no ongoing active infection requiring systemic therapy, and no history of interstitial lung disease. Patients with rapid decline in KPS ( ≥ 10%) or serum albumin ( ≥ 20%) during the 14 day screening period prior to study randomization were ineligible.

A total of 861 patients were randomized (1:1) to the ABRAXANE/gemcitabine arm (N=431) or to the gemcitabine arm (N=430). Randomization was stratified by geographic region (Australia, Western Europe, Eastern Europe, or North America), KPS (70 to 80 versus 90 to 100), and presence of liver metastasis (yes versus no). Patients randomized to ABRAXANE/gemcitabine received ABRAXANE 125 mg/m² as an intravenous infusion over 30-40 minutes followed by gemcitabine 1000 mg/m² as an intravenous infusion over 30-40 minutes on Days 1, 8, and 15 of each 28-day cycle. Patients randomized to gemcitabine received 1000 mg/m² as an intravenous infusion over 30-40 minutes weekly for 7 weeks followed by a 1-week rest period in Cycle 1 then as 1000 mg/m² on Days 1, 8 and 15 of each subsequent 28-day cycle. Patients in both arms received treatment until disease progression or unacceptable toxicity. The major efficacy outcome measure was overall survival (OS). Additional outcome measures were progression-free survival (PFS) and overall response rate (ORR), both assessed by independent, central, blinded radiological review using RECIST (version 1.0).

In the intent to treat (all randomized) population, the median age was 63 years (range 27-88 years) with 42% ≥ 65 years of age; 58% were men; 93% were White and KPS was 90-100 in 60%. Disease characteristics included 46% of patients with 3 or more metastatic sites; 84% of patients had liver metastasis; and the location of the primary pancreatic lesion was in the head of pancreas (43%), body (31%), or tail (25%).

Results for overall survival, progression-free survival, and overall response rate are shown in Table 13.

Table 13: Efficacy Results from Randomized Study in Patients with Adenocarcinoma of the Pancreas (ITT Population)

In exploratory analyses conducted in clinically relevant subgroups with a sufficient number of subjects, the treatment effects on overall survival were similar to that observed in the overall study population.

Figure 1: Kaplan-Meier Curve of Overall Survival (Intent-to-treat Population)

Abraxane is usually administered by a healthcare provider in a medical setting making it unlikely for an overdose to occur. However, if overdose is suspected, seek emergency medical attention.

>10%

Alopecia (90%)

Neutropenia (<2 x 10^9/L) (80%)

Sensory neuropathy, any (71%)

Abnormal EKG, all patients (60%)

Asthenia (47%)

Myalgia/arthralgia (44%)

AST increased (39%)

Alkaline phosphatase increased (36%)

Abnormal EKG, patients normal at baseline (35%)

Anemia (<11 g/dL) (33%)

Nausea (30%)

Diarrhea (27%)

Infections (24%)

Vomiting (18%)

Dyspnea (12%)

Neutropenia (grade 3-4)

• NSCLC (47%)
• Pancreatic cancer (38%)
• Metastatic breast cancer (34%)

1-10%

Sensory neuropathy, severe (10%)

Edema (10%)

Neutropenia (<0.5 x 10^9/L) (9%)

Cough (7%)

Mucositis (7%)

Bilirubin increased (7%)

Hypotension, during infusion (5%)

Hypersensitivity reactions (4%)

Thrombocytopenia (2%)

Febrile neutropenia (2%)

Bleeding (2%)

Anemia (<8 g/dL) (1%)

Postmarketing Reports

Hypersensitivity: Severe hypersensitivity reactions

Cardiovascular: Congestive heart failure, left ventricular dysfunction, and atrioventricular block; most of the individuals were previously exposed to cardiotoxic drugs, such as anthracyclines, or had underlying cardiac history

Respiratory: Interstitial pneumonia, pulmonary embolism, lung fibrosis

Neurologic: Cranial nerve palsies, vocal cord paresis, autonomic neuropathy resulting in paralytic ileu

Vision Disorders: Persistent optic nerve damage; reduced visual acuity due to cystoid macular edema

Hepatic: Hepatic necrosis and hepatic encephalopathy leading to death

Gastrointestinal: Intestinal obstruction, intestinal perforation, pancreatitis, ischemic colitis, neutropenic enterocolitis (typhlitis)

Injection Site Reaction: Extravasation, severe events such as phlebitis, cellulitis, induration, necrosis, and fibrosis (may be delayed by 7-10 ten days)

Paclitaxel protein-bound can be harmful if it gets in your eyes, mouth, or nose, or on your skin. If skin contact occurs, wash the area with soap and water or rinse the eyes thoroughly with plain water.

You should not receive Abraxane if you have a very low white blood cell count.

You may need frequent medical tests at your doctor's office to be sure Abraxane is not causing harmful effects. Your cancer treatments may be delayed based on the results of these tests.

Abraxane can weaken your immune system. Your blood may need to be tested often.

Abraxane is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting.

Abraxane is usually given for breast cancer once every 3 weeks. For lung cancer or pancreatic cancer, this medicine is given in a 21-day or 28-day treatment cycle, and you may only need to receive the medicine during the first 1 to 2 weeks of each cycle. Follow your doctor's dosing instructions very carefully.

Tell your caregivers if you feel any burning, pain, or swelling around the IV needle when this medicine is injected.

Abraxane can lower blood cells that help your body fight infections and help your blood to clot. Your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests.

Call your doctor for instructions if you miss an appointment for your Abraxane injection.

Common side effects of Abraxane include: infection, severe peripheral sensory neuropathy, bone marrow depression, neutropenia, alopecia, anemia, and peripheral sensory neuropathy. Other side effects include: hypersensitivity reaction. See below for a comprehensive list of adverse effects.

Applies to paclitaxel protein-bound: intravenous powder for injection

Dermatologic

Very common (10% or more): Alopecia (90%), rash
Common (1% to 10%): Nail disorder, pruritus, dry skin, erythema, nail pigmentation/discoloration, skin hyperpigmentation, onycholysis, nail changes
Uncommon (0.1% to 1%): Nail bed tenderness, urticaria, skin pain, photosensitivity reaction, pigmentation disorder, pruritic rash, skin disorder, hyperhidrosis, onychomadesis, erythematous rash, generalized rash, dermatitis, night sweats, maculopapular rash, vitiligo, hypotrichosis, nail discomfort, generalized pruritus, macular rash, papular rash, skin lesion, swollen face
Very rare (less than 0.01%): Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN)[Ref]

Hematologic

Very common (10% or more): Neutropenia (up to 82%), anemia (up to 25%), leukopenia, thrombocytopenia, lymphopenia, bone marrow suppression
Common (1% to 10%): Febrile neutropenia
Rare (less than 0.1%): Pancytopenia[Ref]

Nervous system

Very common (10% or more): Peripheral neuropathy, neuropathy, hypoesthesia, paresthesia
Common (1% to 10%): Peripheral sensory neuropathy, headache, dysgeusia, dizziness, peripheral motor neuropathy, ataxia, sensory disturbance, somnolence
Uncommon (0.1% to 1%): Polyneuropathy, areflexia, dyskinesia, hyporeflexia, neuralgia, sensory loss, syncope, postural dizziness, neuropathic pain, tremor, abnormal gait[Ref]

Cardiovascular

Very common (10% or more): Abnormal ECG (60%) including abnormal ECG in patients with a normal baseline (35%)
Common (1% to 10%): Tachycardia, arrhythmia, supraventricular tachycardia, flushing, hot flushes, hypertension, lymphedema, peripheral edema, chest pain
Uncommon (0.1% to 1%): Hypotension, peripheral coldness, orthostatic hypotension, chest discomfort, increased blood pressure
Rare (less than 0.1%): Bradycardia, cardiac arrest, left ventricular dysfunction, congestive heart failure, atrioventricular block, thrombosis[Ref]

Musculoskeletal

Very common (10% or more): Arthralgia/myalgia (44%)
Common (1% to 10%): Pain in extremity, bone pain, back pain, muscle cramps, limb pain, rigors
Uncommon (0.1% to 1%): Chest wall pain, muscular weakness, neck pain, groin pain, muscle spasms, musculoskeletal pain, flank pain, limb discomfort, muscle weakness[Ref]

Hepatic

Very common (10% or more): AST (SGOT) elevations (39%), alkaline phosphatase elevations (36%), gamma-glutamyl transpeptidase (GGT) elevations (14%) patients
Common (1% to 10%): Bilirubin elevations
Uncommon (0.1% to 1%): Hepatomegaly
Rare (less than 0.1%): Hepatic necrosis, hepatic encephalopathy[Ref]

Gastrointestinal

Very common (10% or more): Nausea (30%), diarrhea (26%), vomiting (18%), constipation, stomatitis
Common (1% to 10%): Abdominal pain, abdominal distension, upper abdominal pain, dyspepsia, gastroesophageal reflux disease, oral hypoesthesia, mucosal inflammation
Uncommon (0.1% to 1%): Dysphagia, flatulence, glossodynia, dry mouth, gingival pain, esophagitis, lower abdominal pain, mouth ulceration, oral pain, rectal hemorrhage
Rare (less than 0.1%): Intestinal obstruction, intestinal perforation, pancreatitis, ischemic colitis, neutropenic enterocolitis[Ref]

Other

Very common (10% or more): Fatigue, asthenia, pyrexia
Common (1% to 10%): Vertigo, pain, edema, weakness, decreased performance status, malaise, lethargy, hyperpyrexia
Uncommon (0.1% to 1%): Ear pain, tinnitus[Ref]

Respiratory

Common (1% to 10%): Upper respiratory tract infection, sinusitis, interstitial pneumonitis, dyspnea, epistaxis, pharyngolaryngeal pain, cough, rhinitis, rhinorrhea
Uncommon (0.1% to 1%): Nasopharyngitis, pneumonia, productive cough, exertional dyspnea, sinus congestion, decreased breath sounds, pleural effusion, allergic rhinitis, hoarseness, nasal congestion, nasal dryness, wheezing, pulmonary emboli, pulmonary thromboembolism[Ref]

Hypersensitivity

Very common (10% or more): Hypersensitivity (up to 12%)
Rare (less than 0.1%): Severe hypersensitivity[Ref]

Local

Uncommon (0.1% to 1%): Swelling, injection site reaction
Rare (0.01% to 0.1%): Extravasation[Ref]

Ocular

Common (1% to 10%): Increased lacrimation, blurred vision, dry eye, keratoconjunctivitis sicca, madarosis
Uncommon (0.1% to 1%): Eye irritation, eye pain, abnormal vision, reduced visual acuity, conjunctivitis, visual disturbance, eye pruritus, keratitis
Rare (less than 0.1%): Cystoid macular edema[Ref]

Genitourinary

Common (1% to 10%): Urinary tract infection
Uncommon (0.1% to 1%): Dysuria, pollakiuria, hematuria, nocturia, polyuria, urinary incontinence, breast pain[Ref]

Metabolic

Very common (10% or more): Anorexia
Common (1% to 10%): Dehydration, hypokalemia, weight loss, increased alanine aminotransferase, increased aspartate aminotransferase, increased gamma-glutamyltransferase, decreased hematocrit, decreased red blood cell count, increased blood alkaline phosphatase
Uncommon (0.1% to 1%): Hypophosphatasemia, fluid retention, hypoalbuminemia, polydipsia, hyperglycemia, hypocalcemia, hypoglycemia, hyponatremia, weight gain, increased blood lactate dehydrogenase, increased blood creatinine, increased blood glucose, increased blood phosphorus, decreased blood potassium, increased bilirubin[Ref]

Oncologic

Uncommon (0.1% to 1%): Metastatic pain, tumor necrosis[Ref]

Psychiatric

Common (1% to 10%): Insomnia, depression, anxiety
Uncommon (0.1% to 1%): Restlessness[Ref]

Immunologic

Very common (10% or more): Infections (up to 24%)
Common (1% to 10%): Febrile neutropenia, folliculitis, candidiasis, influenza-like illness
Uncommon (0.1% to 1%): Neutropenic sepsis, oral candidiasis, cellulitis, herpes simplex, viral infection, catheter-related infection, fungal infection, herpes zoster, injection site infection, sepsis, neutropenic sepsis[Ref]

Some side effects of Abraxane may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

135 mg/m2 IV over 24 hours followed by cisplatin every 3 weeks

Comment:
-All patients should be premedicated prior to receiving this drug to prevent severe hypersensitivity reactions. Consult the manufacturer product information or local protocol for premedication guidelines.

Use: For the first-line treatment of non-small cell lung cancer in combination with cisplatin in patients who are not candidates for potentially curative surgery and/or radiation therapy

For patients with AIDS-Related Kaposi's Sarcoma:
135 mg/m2 IV over 3 hours every 3 weeks
OR
100 mg/m2 IV over 3 hours every 2 weeks

Note: In patients with advanced HIV disease:
1) Reduce the dose of dexamethasone as one of the premedication drugs (consult the manufacturer product information).
2) Initiate or repeat treatment with this drug only if the neutrophil count is at least 1000 cells/mm3.
3) Reduce the dose of subsequent courses of this drug by 20% for patients who experience severe neutropenia (a neutrophil count less than 500 cells/mm3 for a week or longer).
4) Initiate concomitant hematopoietic growth factor (G-CSF) as clinically indicated.

Comment:
-All patients should be premedicated prior to receiving this drug to prevent severe hypersensitivity reactions. Consult the manufacturer product information or local protocol for premedication guidelines.

Use: For the second-line treatment of AIDS-related Kaposi's sarcoma