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  • CLASSES

    Taxanes

    BOXED WARNING

    Bone marrow suppression, neutropenia, thrombocytopenia

    Bone marrow suppression (e.g., neutropenia, thrombocytopenia) is the dose-limiting toxicity of nanoparticle albumin-bound (nab) paclitaxel. Nab-paclitaxel is contraindicated in patients with a baseline absolute neutrophil count (ANC) of less than 1,500 cells/mm3. Obtain a complete blood count (CBC) panel prior to starting a new cycle of nab-paclitaxel therapy on day 1 in all patients and prior to therapy on day 8 and 15 in patients with non-small cell lung cancer and pancreatic cancer. Do not resume a new cycle of therapy until the ANC is 1,500 cells/mm3 or more and the platelet count is 100,000 cells/mm3 or more. In patients who develop severe neutropenia or thrombocytopenia, hold nab-paclitaxel and reduce the dose of therapy for subsequent cycles as recommended for the particular indication of use and chemotherapy regimen.

    DEA CLASS

    Rx

    DESCRIPTION

    Nanoparticle albumin-bound taxane; a microtubule inhibitor
    Used for metastatic breast cancer, locally advanced or metastatic NSCLC, and metastatic pancreatic cancer
    Do not start a new cycle if ANC is less than 1,500 cells/mm3; myelosuppression requires monitoring and possible adjustments in therapy

    COMMON BRAND NAMES

    Abraxane

    HOW SUPPLIED

    Abraxane Intravenous Inj Pwd F/Susp: 100mg

    DOSAGE & INDICATIONS

    For the treatment of breast cancer.
    For metastatic breast cancer after the failure of combination chemotherapy or relapse within 6 months of adjuvant chemotherapy.
    NOTE: Prior therapy should have included an anthracycline unless clinically contraindicated. 
    Intravenous dosage
    Adults

    260 mg/m2 IV over 30 minutes every 3 weeks. The primary endpoint of overall response rate (ORR) was significantly improved with nab-paclitaxel compared with standard paclitaxel (33% vs. 19%; p = 0.001) administered every 3 weeks in patients with metastatic breast cancer in a multicenter, randomized, phase III trial (n = 460). Additionally, the median time to progression (TTP) was significantly longer with nab-paclitaxel compared with standard paclitaxel (23 weeks vs. 16.9 weeks; hazard ratio = 0.75; p = 0.006). The TTP was significantly longer in patients treated with nab-paclitaxel as second line or greater (20.9 weeks vs. 16.1 weeks; p = 0.02) but not as first line (24 weeks vs. 19.7 weeks) therapy. The median overall survival (OS) time was not significantly improved with nab-paclitaxel compared with standard paclitaxel (65 weeks vs. 55.7 weeks); however, the median OS time was significantly improved in the subpopulation of patients treated with nab-paclitaxel as second line or greater (56.4 weeks vs. 46.7 weeks; p = 0.024).

    For the treatment of taxane-refractory metastatic breast cancer†.
    Intravenous dosage
    Adults

    100 mg/m2 IV over 30 minutes once per week for 3 weeks, then 1 week off, every 28 days. In a phase II, open-label non-randomized study of taxane-refractory metastatic breast cancer patients, 14% achieved a response and 12% had stable disease.

    For the treatment of previously untreated metastatic breast cancer†.
    Intravenous dosage
    Adults

    100 mg/m2 to 150 mg/m2 IV over 30 minutes once per week for 3 weeks, then 1 week off, every 28 days. In a phase 2 trial, 302 patients with previously untreated metastatic breast cancer were randomized to receive nab-paclitaxel 100 mg/m2 or 150 mg/m2 weekly for 3 out of 4 weeks, nab-paclitaxel 300 mg/m2 once every 3 weeks, or docetaxel 100 mg/m2 once every 3 weeks. Overall response rate, the primary endpoint, was not significantly different between the groups. However, when reviewed by an independent radiologist, progression-free survival (PFS) was significantly improved in the nab-paclitaxel 150 mg/m2 arm vs. docetaxel (12.9 months vs. 7.5 months) and in the nab-paclitaxel 100 mg/m2 arm (12.8 months vs. 7.5 months); in the nab-paclitaxel 300 mg/m2 every 3 weeks arm PFS was 11 months.

    For the first-line treatment of locally advanced or metastatic, hormone-receptor (HR)-negative, HER2-negative (triple-negative) breast cancer, in combination with atezolizumab†.
    NOTE: Do not substitute nab-paclitaxel with paclitaxel. In a phase 3 clinical trial (the IMpassion131 trial), treatment with atezolizumab and paclitaxel did not significantly reduce the risk of cancer progression and death compared with placebo and paclitaxel in the PD-L1-positive population; interim overall survival results favored paclitaxel plus placebo over paclitaxel plus atezolizumab in both the PD-L1-positive population and total population.
    NOTE: Atezolizumab is FDA-approved for this indication in combination with nab-paclitaxel.
    Intravenous dosage
    Adults

    100 mg/m2 IV over 30 minutes on days 1, 8, and 15, in combination with atezolizumab 840 mg IV over 60 minutes on days 1 and 15, repeated every 28 days until disease progression or unacceptable toxicity. In the absence of disease progression, nab-paclitaxel should be continued for at least 6 cycles. If the first atezolizumab infusion is tolerated, all subsequent atezolizumab infusions may be infused over 30 minutes. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. First-line treatment with atezolizumab plus nab-paclitaxel significantly improved progression-free survival (PFS) compared with placebo plus nab-paclitaxel in the first interim analysis of a phase 3 clinical trial. Overall survival was not significantly improved in the intent-to-treat population, and testing was not performed in the PD-L1 positive subgroup; however, numerical improvements were evident in both groups, and the final analysis may shed more light on this outcome.

    For the treatment of non-small cell lung cancer (NSCLC).
    For the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) in patients who are not candidates for curative surgery or radiation, in combination with carboplatin.
    Intravenous dosage
    Adults

    100 mg/m2 IV over 30 minutes on days 1, 8, and 15 in combination with carboplatin (AUC 6 IV) on day 1 (immediately following the nab-paclitaxel infusion) of each 21-day cycle. The primary endpoint of overall response rate (ORR) assessed by independent radiologic review was significantly improved with nab-paclitaxel plus carboplatin (median number of cycles, 6) compared with solvent-based (sb) paclitaxel plus carboplatin (33% vs. 25%) in patients with previously untreated non-resectable stage IIIB or stage IV NSCLC in a multicenter, randomized, phase 3 trial (n = 1,052). All responding patients in the nab-paclitaxel arm had a partial response (PR); one patient in the sb-paclitaxel arm achieved a complete response, all others had a PR. In a subgroup analysis, the ORR was significantly improved with nab-paclitaxel plus carboplatin in patients with squamous cell histology (41% vs. 24%) but not nonsquamous cell histology (26% vs. 25%). Although treatment with nab-paclitaxel plus carboplatin was not statistically superior compared with sb-paclitaxel plus carboplatin for the secondary endpoints of median progression-free survival (6.3 months vs. 5.8 months) and overall survival (12.1 months vs. 11.2 months), noninferiority was demonstrated.

    For the first-line treatment of metastatic squamous non-small cell lung cancer (NSCLC), in combination with carboplatin and pembrolizumab.
    Intravenous dosage
    Adults

    100 mg/m2 IV on days 1, 8, and 15 and carboplatin (AUC 6 IV on day 1) repeated every 3 weeks for 4 cycles in combination with pembrolizumab (200 mg IV every 3 weeks OR 400 mg IV every 6 weeks until disease progression or up to a maximum of 24 months). Administer pembrolizumab prior to chemotherapy when given on the same day. Pembrolizumab therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. In a multicenter, randomized, double-blind clinical trial, treatment with pembrolizumab plus carboplatin and either paclitaxel or nab-paclitaxel (n = 278) significantly improved median overall survival (15.9 months vs. 11.3 months) and progression-free survival (6.4 months vs. 4.8 months) compared with placebo plus carboplatin and paclitaxel/nab-paclitaxel (n = 281) in patients with metastatic squamous NSCLC. The overall response rate was also significantly improved in the pembrolizumab arm (58% vs. 35%), for a median duration of 7.2 months and 4.9 months, respectively.

    For the first-line treatment of metastatic nonsquamous non-small cell lung cancer (NSCLC) without EGFR or ALK mutations, in combination with atezolizumab and carboplatin.
    NOTE: Atezolizumab is FDA-approved in combination with nab-paclitaxel and carboplatin for this indication.
    Intravenous dosage
    Adults

    100 mg/m2 IV over 30 minutes on days 1, 8, and 15, in combination with atezolizumab (1,200 mg IV over 60 minutes on day 1) and carboplatin (AUC 6 IV on day 1), every 3 weeks for a maximum of 4 to 6 cycles of chemotherapy. Administer atezolizumab prior to chemotherapy when given on the same day. After completion of 4 to 6 cycles of chemotherapy, continue atezolizumab monotherapy at a dose of 840 mg IV every 2 weeks; 1,200 mg IV every 3 weeks; OR 1,680 mg IV every 4 weeks. First-line treatment of EGFR- and ALK-negative metastatic NSCLC with atezolizumab plus nab-paclitaxel and carboplatin significantly improved median overall survival (18.6 months vs. 13.9 months) and median progression-free survival (7.2 months vs. 6.5 months) compared with nab-paclitaxel and carboplatin alone in a multicenter, randomized, open-label trial (Impower130). The overall response rate was 46% (complete response [CR], 5%) in the atezolizumab arm compared with  32% (CR, 1%) in the control arm, for a median duration of 10.8 months versus 7.8 months, respectively.

    For the first-line treatment of metastatic pancreatic cancer in combination with gemcitabine.
    Intravenous dosage
    Adults

    125 mg/m2 IV over 30 to 40 minutes on days 1, 8, and 15 followed by gemcitabine (1,000 mg/m2 IV over 30 to 40 minutes on days 1, 8, and 15), every 28 days. In a multinational, randomized, open-label study, nab-paclitaxel plus gemcitabine (n = 431) was compared to gemcitabine 1,000 mg/m2 IV weekly for 7 weeks with a 1 week rest period in cycle 1, and then on days 1, 8, and 15 of each subsequent 28 day cycle (n = 430) until disease progression or unacceptable toxicity in patients with metastatic adenocarcinoma of the pancreas. Median overall survival (8.5 months vs. 6.7 months) and median progression free survival (5.5 months vs. 3.7 months) were significantly improved by the combination of nab-paclitaxel and gemcitabine. Additionally, 23% of patients treated with combination therapy had a confirmed complete or partial overall response, compared to 7% of patients treated with gemcitabine alone.

    MAXIMUM DOSAGE

    Adults

    260 mg/m2 IV.

    Geriatric

    260 mg/m2 IV.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Baseline Hepatic Impairment
    Metastatic Breast Cancer
    Mild hepatic impairment (AST 10 times the upper limit of normal (ULN) or less and total bilirubin 1.5 times ULN or less): No dose adjustment is necessary. Base the need for subsequent dose adjustments on individual patient tolerance.
    Moderate hepatic impairment (AST less than 10 times ULN and total bilirubin 1.6 to 3 times ULN): Reduce the dose of nab-paclitaxel to 200 mg/m2; if this dose is tolerated for 2 cycles, consider an increase to the full dose of 260 mg/m2 in subsequent cycles. Base the need for subsequent dose adjustments on individual patient tolerance.
    Severe hepatic impairment (AST less than 10 times ULN and total bilirubin 3.1 to 5 times ULN): Reduce the dose of nab-paclitaxel to 200 mg/m2; if this dose is tolerated for 2 cycles, consider an increase to the full dose of 260 mg/m2 in subsequent cycles. Base the need for subsequent dose adjustments on individual patient tolerance.
    AST greater than 10 times ULN or total bilirubin greater than 5 times ULN: The use of nab-paclitaxel is not recommended.
     
    Non-Small Cell Lung Cancer (NSCLC)
    NOTE: Patients with bilirubin levels above the upper limit of normal were excluded from clinical trials for NSCLC.
    Mild hepatic impairment (AST 10 times the upper limit of normal (ULN) or less and total bilirubin 1.5 times ULN or less): No dose adjustment is necessary. Base the need for subsequent dose adjustments on individual patient tolerance.
    Moderate hepatic impairment (AST less than 10 times ULN and total bilirubin 1.6 to 3 times ULN): Reduce the dose of nab-paclitaxel to 80 mg/m2; if this dose is tolerated for 2 cycles, consider an increase to the full dose of 100 mg/m2 in subsequent cycles. Base the need for subsequent dose adjustments on individual patient tolerance.
    Severe hepatic impairment (AST less than 10 times ULN and total bilirubin 3.1 to 5 times ULN): Reduce the dose of nab-paclitaxel to 80 mg/m2; if this dose is tolerated for 2 cycles, consider an increase to the full dose of 100 mg/m2 in subsequent cycles. Base the need for subsequent dose adjustments on individual patient tolerance.
    AST greater than 10 times ULN or total bilirubin greater than 5 times ULN: The use of nab-paclitaxel is not recommended.
     
    Pancreatic Adenocarcinoma
    NOTE: Patients with bilirubin levels above the upper limit of normal were excluded from clinical trials for pancreatic cancer.
    Mild hepatic impairment (AST 10 times the upper limit of normal (ULN) or less and total bilirubin 1.5 times ULN or less): No dose adjustment is necessary. Base the need for subsequent dose adjustments on individual patient tolerance.
    Moderate hepatic impairment (AST less than 10 times ULN and total bilirubin 1.6 to 3 times ULN): The use of nab-paclitaxel is not recommended.
    Severe hepatic impairment (AST less than 10 times ULN and total bilirubin 3.1 to 5 times ULN): The use of nab-paclitaxel is not recommended.
    AST greater than 10 times ULN or total bilirubin greater than 5 times ULN: The use of nab-paclitaxel is not recommended.

    Renal Impairment

    Baseline Renal Impairment
    Mild to moderate renal impairment (CrCl 30 to 89 mL/min): No adjustment to the starting dose of nab-paclitaxel is necessary.
    Severe renal impairment or end-stage renal disease (CrCl less than 30 mL/min): Insufficient data exist to make dosage recommendations.

    ADMINISTRATION

    CAUTION: Observe and exercise usual precautions for handling, preparing, and administering solutions of cytotoxic drugs. If nanoparticle albumin-bound (nab) paclitaxel comes in contact with the skin, wash the affected area immediately and thoroughly with soap and water. Following topical exposure, tingling, burning, and redness may occur. If contact occurs with mucous membranes, flush the affected area thoroughly with water.
    For storage information, see specific product information within the How Supplied section.

    Injectable Administration

    Visually inspect parenteral product prior to administration; discard if proteinaceous strands, particulate matter, or discoloration are observed.

    Intravenous Administration

    Administer as an intravenous (IV) infusion over 30 minutes. Limiting the infusion time to 30 minutes reduces the likelihood of infusion-related reactions.
    Each single-use 100-mg vial contains approximately 900 mg of human albumin.
    Substitution for (or with) other paclitaxel formulations is prohibited. The albumin formulation of nab-paclitaxel significantly affects the volume of distribution, exposure, and clearance of unbound drugs relative to those of solvent-based paclitaxel.
    Consider premedication for patients who have had prior hypersensitivity reactions to nab-paclitaxel.
     
    Reconstitution
    Slowly inject 20 mL of 0.9% Sodium Chloride Injection, USP onto the inside wall of the vial of lyophilized powder over a minimum of 1 minute.
    Do not inject the 0.9% Sodium Chloride Injection, USP direction onto the lyophilized cake as this will cause foaming.
    Allow the vial to sit for a minimum of 5 minutes to ensure proper wetting of the lyophilized cake/powder.
    Gently swirl and/or invert the vial slowly for at least 2 minutes until complete dissolution occurs; avoid the generation of foam.
    If foaming or clumping occurs, allow the solution to stand for at least 15 minutes until the foam subsides.
    The reconstituted suspension should be milky and homogenous without visible particles. If particulates or settling are visible, gently invert the vial again to ensure complete resuspension prior to use. Each mL of the reconstituted suspension contains 5 mg/mL of paclitaxel.
    Stability after reconstitution: Use immediately if possible. If not used immediately, each reconstituted vial should be replaced in the original carton to protect it from bright light; refrigerate between 2 to 8 degrees C (36 to 46 degrees F) for a maximum of 24 hours. The total combined refrigerated storage time of reconstituted nab-paclitaxel in the vial and in the infusion bag is 24 hours. This may be followed by storage in the infusion bag at ambient temperature (approximately 25 degrees C) and lighting conditions for a maximum of 4 hours.
     
    Dilution
    Inject the appropriate amount of reconstituted nab-paclitaxel into an empty, sterile IV bag (plasticized PVC containers, PVC or non-PVC type IV bag).
    It is not necessary to use specialized DEHP-free solution containers or administration sets for preparation or administration. However, the use of medical devices containing silicone oil as a lubricant (i.e., syringes and IV bags) may result in the formation of proteinaceous strands.
    Stability after dilution: Use immediately if possible. If not used immediately, protect from bright light and refrigerate at 2 to 8 degrees C (36 to 46 degrees F) for a maximum of 24 hours. The total combined refrigerated storage time of reconstituted nab-paclitaxel in the vial and in the infusion bag is 24 hours. This may be followed by storage in the infusion bag at ambient temperature (approximately 25 degrees C) and lighting conditions for a maximum of 4 hours.

    STORAGE

    Abraxane:
    - Do not freeze
    - Do not refrigerate
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in original container

    CONTRAINDICATIONS / PRECAUTIONS

    Albumin hypersensitivity, taxane hypersensitivity

    Patients with a history of taxane hypersensitivity should be closely monitored during the initiation of nanoparticle albumin-bound (nab) paclitaxel therapy; cross-hypersensitivity between nab-paclitaxel and other taxane products has been reported and may include severe reactions such as anaphylaxis. Severe hypersensitivity reactions (e.g., anaphylaxis) have also been reported with nab-paclitaxel use in patients who have not previously received taxane therapy; some cases were fatal. Consider premedication for patients who have had prior hypersensitivity reactions to nab-paclitaxel. Nab-paclitaxel is contraindicated in patients who have experienced a severe hypersensitivity to the product; these patients should not be rechallenged. Also use caution in patients with an albumin hypersensitivity, as nab-paclitaxel is formulated with human albumin.

    Ensure correct formulation selection

    Ensure correct formulation selection and do not substitute nab-paclitaxel for or with other paclitaxel formulations. Exposure to unbound paclitaxel is significantly higher with nanoparticle albumin-bound (nab) paclitaxel compared to solvent-based paclitaxel when total exposure is comparable. The drug clearance of nab-paclitaxel is also higher and volume of distribution, larger, than for solvent-based paclitaxel.

    Bone marrow suppression, neutropenia, thrombocytopenia

    Bone marrow suppression (e.g., neutropenia, thrombocytopenia) is the dose-limiting toxicity of nanoparticle albumin-bound (nab) paclitaxel. Nab-paclitaxel is contraindicated in patients with a baseline absolute neutrophil count (ANC) of less than 1,500 cells/mm3. Obtain a complete blood count (CBC) panel prior to starting a new cycle of nab-paclitaxel therapy on day 1 in all patients and prior to therapy on day 8 and 15 in patients with non-small cell lung cancer and pancreatic cancer. Do not resume a new cycle of therapy until the ANC is 1,500 cells/mm3 or more and the platelet count is 100,000 cells/mm3 or more. In patients who develop severe neutropenia or thrombocytopenia, hold nab-paclitaxel and reduce the dose of therapy for subsequent cycles as recommended for the particular indication of use and chemotherapy regimen.

    Peripheral neuropathy

    Peripheral neuropathy has been reported commonly with nab-paclitaxel use. Sensory neuropathy is dose-and schedule-dependent. An interruption of therapy and dose reduction is necessary for grade 3 or higher sensory neuropathy, with specific recommendations differing according to indication.

    Biliary obstruction, fever, sepsis

    Patients with biliary obstruction or who have a biliary stent may be at increased risk for severe or fatal sepsis when treated with nab-paclitaxel in combination with gemcitabine. If a patient develops a fever (regardless of ANC), initiate appropriate broad-spectrum antibiotics. If febrile neutropenia occurrs, an interruption of therapy and dose reduction may be necessary.[30742]

    Hepatic disease

    Use nab-paclitaxel cautiously in patients with hepatic disease and/or hyperbilirubinemia, as they are at an increased risk of paclitaxel-associated toxicity, including hematologic toxicity. The starting dose should be reduced for patients breast cancer or NSCLC who have moderate or severe hepatic impairment; nab-paclitaxel is not recommended in patients with metastatic pancreatic cancer who have moderate to severe hepatic impairment (total bilirubin more than 1.5 times the upper limit of normal [ULN] and AST 10 times ULN or less). Do not administer nab-paclitaxel to any cancer patient with an AST level greater than 10 times ULN or a bilirubin level greater than 5 times ULN. If nab-paclitaxel is administered to patients with hepatic impairment, monitor closely for the development of severe myelosuppression.

    Chronic lung disease (CLD), pneumonitis, pulmonary disease

    Use nab-paclitaxel with caution in patients with a history of pulmonary disease or chronic lung disease (CLD). In clinical trials, 4% of patients treated with nab-paclitaxel and gemcitabine developed pneumonitis; some cases were fatal. Interrupt nab-paclitaxel and gemcitabine if patients develop shortness of breath (dyspnea), cough, and chest pain until the patient is evaluated. Permanently discontinue treatment with nab-paclitaxel and gemcitabine if pneumonitis is diagnosed and an infectious cause of the pulmonary symptoms is eliminated.

    Viral infection

    Nab-paclitaxel carries a risk for transmission of viral infection because it contains human albumin, a derivative of human blood; a theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) also exists. Due to effective donor screening and product manufacturing processes, the risk of transmission of viral infection or CJD is considered to be extremely remote; no cases of transmission of viral diseases or CJD have been identified for albumin.

    Geriatric

    Use caution when treating geriatric patients (65 years and older) with nab-paclitaxel. An increased incidence of some adverse effects, including arthralgia, decreased appetite, dehydration, diarrhea, epistaxis, fatigue, myelosuppression, peripheral neuropathy, and peripheral edema were reported more often in patients 65 years or older compared with younger adult patients in 3 separate randomized trials (n = 1,926). Toxicity was similar among geriatric patients and younger patients with metastatic breast cancer who received nab-paclitaxel in another randomized study (n = 229).

    Extravasation

    Closely monitor the infusion site for possible infiltration and extravasation during the administration of nab-paclitaxel. If nab-paclitaxel (as lyophilized cake, reconstituted suspension, or IV solution) contacts the skin, wash the skin immediately and thoroughly with soap and water; tingling, burning, and redness may occur. If nab-paclitaxel contacts mucous membranes, flush thoroughly with water.

    Accidental exposure

    Nab-paclitaxel is a cytotoxic drug; the use of gloves during administration is recommended. Upon accidental exposure to nab-paclitaxel (either the lyophilized cake or reconstituted suspension), wash the skin immediately and thoroughly with soap and water. Following topical exposure, events may include tingling, burning, and redness. Shortness of breath, chest pain, burning eyes, and sore throat have been reported upon inhalation of paclitaxel.

    Pregnancy

    Pregnancy should be avoided by females of reproductive potential during nab-paclitaxel treatment and for at least 6 months after the last dose. Although there are no adequately controlled studies in pregnant humans, nab-paclitaxel can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Women who are pregnant or who become pregnant while receiving nab-paclitaxel should be apprised of the potential hazard to the fetus. In animal reproduction studies, administration of nab-paclitaxel to pregnant rats during organogenesis resulted in embryo-fetal toxicity at doses approximately 2% of the maximum recommended human dose (MRHD) on a mg/m2 basis. These toxicities included intrauterine mortality, increased resorptions (up to 5-fold), reduced numbers of litters and live fetuses, reduced fetal body weight, and increased fetal anomalies such as soft tissue and skeletal malformations (e.g. eye bulge, folded retina, microphthalmia, dilation of brain ventricles).

    Contraception requirements, infertility, male-mediated teratogenicity, pregnancy testing, reproductive risk

    Counsel patients about the reproductive risk and contraception requirements during nab-paclitaxel treatment. Nab-paclitaxel can be teratogenic if taken by the mother during pregnancy. Females of reproductive potential should avoid pregnancy and use effective contraception during and for at least 6 months after treatment with nab-paclitaxel. Male-mediated teratogenicity is also possible. Males with female partners of reproductive potential should avoid fathering a child and use effective contraception during and for at least 3 months after treatment with nab-paclitaxel. Females of reproductive potential should undergo pregnancy testing prior to initiation of nab-paclitaxel. Women who become pregnant while receiving nab-paclitaxel should be apprised of the potential hazard to the fetus. Although there are no data regarding the effect of nab-paclitaxel on human fertility, male and female infertility has been observed in animal studies.

    Breast-feeding

    Due to the potential for serious adverse reactions in nursing infants from nab-paclitaxel, advise women to discontinue breast-feeding during treatment and for 2 weeks after the final dose. It is not known whether nab-paclitaxel is present in human milk, although many drugs are excreted in human milk.

    ADVERSE REACTIONS

    Severe

    neutropenia / Delayed / 34.0-34.0
    fatigue / Early / 18.0-18.0
    peripheral neuropathy / Delayed / 3.0-17.0
    heart failure / Delayed / 0-10.0
    macular edema / Delayed / 0-10.0
    arthralgia / Delayed / 1.0-8.0
    myalgia / Early / 1.0-8.0
    asthenia / Delayed / 7.0-8.0
    dehydration / Delayed / 0-7.0
    vomiting / Early / 4.0-6.0
    nausea / Early / 3.0-6.0
    diarrhea / Early / 0-6.0
    anorexia / Delayed / 5.0-5.0
    hypokalemia / Delayed / 0-4.0
    fever / Early / 3.0-3.0
    cystitis / Delayed / 0-2.0
    anemia / Delayed / 1.0-1.0
    thrombocytopenia / Delayed / 0-1.0
    bradycardia / Rapid / 0-1.0
    alopecia / Delayed / 1.0-1.0
    stomatitis / Delayed / 1.0-1.0
    visual impairment / Early / 0-1.0
    keratitis / Delayed / 0-1.0
    blurred vision / Early / 0-1.0
    headache / Early / 0-1.0
    depression / Delayed / 0-1.0
    renal failure (unspecified) / Delayed / 1.0-1.0
    pancytopenia / Delayed / Incidence not known
    thromboembolism / Delayed / Incidence not known
    pulmonary embolism / Delayed / Incidence not known
    stroke / Early / Incidence not known
    cardiac arrest / Early / Incidence not known
    thrombosis / Delayed / Incidence not known
    pneumothorax / Early / Incidence not known
    pulmonary fibrosis / Delayed / Incidence not known
    cranial nerve palsies / Delayed / Incidence not known
    ileus / Delayed / Incidence not known
    GI perforation / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    typhlitis / Delayed / Incidence not known
    GI obstruction / Delayed / Incidence not known
    hepatic encephalopathy / Delayed / Incidence not known
    hepatic necrosis / Delayed / Incidence not known
    tumor lysis syndrome (TLS) / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known

    Moderate

    peripheral edema / Delayed / 10.0-43.0
    elevated hepatic enzymes / Delayed / 14.0-39.0
    constipation / Delayed / 0-16.0
    dyspnea / Early / 12.0-12.0
    edema / Delayed / 0-10.0
    sinus tachycardia / Rapid / 0-10.0
    hypertension / Early / 0-10.0
    candidiasis / Delayed / 0-10.0
    hyperbilirubinemia / Delayed / 7.0-7.0
    hypotension / Rapid / 1.0-5.0
    pneumonitis / Delayed / 0-4.0
    chest pain (unspecified) / Early / 1.0-3.0
    bleeding / Early / 2.0-2.0
    bone marrow suppression / Delayed / Incidence not known
    supraventricular tachycardia (SVT) / Early / Incidence not known
    phlebitis / Rapid / Incidence not known
    paresis / Delayed / Incidence not known
    colitis / Delayed / Incidence not known
    conjunctivitis / Delayed / Incidence not known

    Mild

    infection / Delayed / 24.0-24.0
    cough / Delayed / 7.0-17.0
    dysgeusia / Early / 0-16.0
    epistaxis / Delayed / 7.0-15.0
    injection site reaction / Rapid / Incidence not known
    lacrimation / Early / Incidence not known

    DRUG INTERACTIONS

    Abiraterone: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with abiraterone is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and abiraterone is a weak CYP2C8 inhibitor.
    Acetaminophen; Butalbital: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with butalbital is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and butalbital is a moderate CYP3A4 inducer.
    Acetaminophen; Butalbital; Caffeine: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with butalbital is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and butalbital is a moderate CYP3A4 inducer.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with butalbital is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and butalbital is a moderate CYP3A4 inducer.
    Amiodarone: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with amiodarone is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and amiodarone is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Amobarbital: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with amobarbital is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and amobarbital is a moderate CYP3A4 inducer.
    Amoxicillin; Clarithromycin; Lansoprazole: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with clarithromycin is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with clarithromycin is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Apalutamide: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with apalutamide is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer.
    Aprepitant, Fosaprepitant: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with a 3-day oral regimen of aprepitant is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and aprepitant, administered orally over 3 days, is a moderate CYP3A4 inhibitor. Single oral doses of aprepitant and intravenous doses of fosaprepitant have not been shown to alter concentrations of CYP3A4 substrates.
    Armodafinil: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with armodafinil is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and armodafinil is a weak CYP3A4 inducer.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with butalbital is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and butalbital is a moderate CYP3A4 inducer.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with butalbital is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and butalbital is a moderate CYP3A4 inducer.
    Atazanavir: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with atazanavir is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Atazanavir; Cobicistat: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with atazanavir is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors. (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with cobicistat is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with phenobarbital is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with phenobarbital is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer.
    Bexarotene: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with bexarotene is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer.
    Bosentan: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with bosentan is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and bosentan is a moderate CYP3A4 inducer.
    Brigatinib: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with brigatinib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and brigatinib is a moderate CYP3A4 inducer.
    Butabarbital: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with butabarbital is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and butabarbital is a moderate CYP3A4 inducer.
    Cannabidiol: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with cannabidiol is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and cannabidiol is a weak CYP2C8 inhibitor.
    Carbamazepine: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with carbamazepine is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
    Cenobamate: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with cenobamate is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and cenobamate is a moderate CYP3A4 inducer.
    Ceritinib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with ceritinib is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Chloramphenicol: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with chloramphenicol is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Ciprofloxacin: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with ciprofloxacin is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and ciprofloxacin is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Clarithromycin: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with clarithromycin is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Clobazam: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with clobazam is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and clobazam is a weak CYP3A4 inducer.
    Clopidogrel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with clopidogrel is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and clopidogrel is a strong CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8.
    Cobicistat: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with cobicistat is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Conivaptan: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with conivaptan is necessary due to the risk of increased plasma concentrations of paclitaxel; consider a washout period of 1 week after the infusion of conivaptan before administering nab-paclitaxel if possible. Nab-paclitaxel is a CYP3A4 substrate and conivaptan is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Crizotinib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with crizotinib is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and crizotinib is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Cyclosporine: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with cyclosporine is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and cyclosporine is a moderate CYP3A4 inhibitor. In vitro, the metabolism of paclitaxel is inhibited by cyclosporine at concentrations that exceed those found in vivo following normal therapeutic doses.
    Dabrafenib: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with dabrafenib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer.
    Danazol: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with danazol is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Darunavir: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with darunavir is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Darunavir; Cobicistat: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with cobicistat is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors. (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with darunavir is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with cobicistat is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors. (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with darunavir is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with ritonavir is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Deferasirox: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with deferasirox is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and deferasirox is a moderate CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8.
    Delavirdine: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with delavirdine is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Dexamethasone: (Moderate) Monitor for decreased efficacy of nab-paclitaxel or increased paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with dexamethasone is necessary. Nab-paclitaxel is a CYP3A4 substrate and dexamethasone is a moderate CYP3A4 inducer; plasma concentrations of dexamethasone may decrease. In vitro however, the metabolism of paclitaxel is inhibited by dexamethasone at concentrations that exceed those found in vivo following normal therapeutic doses.
    Diltiazem: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with diltiazem is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and diltiazem is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Dronedarone: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with dronedarone is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and dronedarone is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Duvelisib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with duvelisib is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Efavirenz: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with efavirenz is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and efavirenz is a moderate CYP3A4 inducer.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with efavirenz is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and efavirenz is a moderate CYP3A4 inducer.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with efavirenz is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and efavirenz is a moderate CYP3A4 inducer.
    Elagolix: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with elagolix is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and elagolix is a weak-to-moderate CYP3A4 inducer.
    Elagolix; Estradiol; Norethindrone acetate: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with elagolix is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and elagolix is a weak-to-moderate CYP3A4 inducer.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with cobicistat is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with cobicistat is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Enzalutamide: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with enzalutamide is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer.
    Erlotinib: (Moderate) The use of taxane-based chemotherapy with erlotinib appears to be one of the risk factors for gastrointestinal (GI) perforation with erlotinib. Monitor for symptoms of GI perforation (e.g., severe abdominal pain, fever, nausea, and vomiting) if coadministration of erlotinib with a taxane chemotherapy agent is necessary.
    Erythromycin: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with erythromycin is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Erythromycin; Sulfisoxazole: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with erythromycin is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Eslicarbazepine: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with eslicarbazepine is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer.
    Etravirine: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with etravirine is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer.
    Fedratinib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with fedratinib is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and fedratinib is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Fluconazole: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with fluconazole is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and fluconazole is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Fluoxetine: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with fluoxetine is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate; fluoxetine is a weak inhibitor of CYP3A4, but its metabolite norfluoxetine is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Fluoxetine; Olanzapine: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with fluoxetine is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate; fluoxetine is a weak inhibitor of CYP3A4, but its metabolite norfluoxetine is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Fosamprenavir: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with fosamprenavir is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and fosamprenavir is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Fosphenytoin: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with fosphenytoin is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and fosphenytoin is a strong CYP3A4 inducer.
    Gemfibrozil: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with gemfibrozil is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and gemfibrozil is a strong CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8.
    Grapefruit juice: (Major) Advise patients to avoid grapefruit juice while taking nab-paclitaxel due to the risk of increased paclitaxel exposure. Nab-paclitaxel is a CYP3A4 substrate and grapefruit juice is a strong CYP3A4 inhibitor.
    Idelalisib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with idelalisib is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Imatinib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with imatinib is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Indinavir: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with indinavir is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and indinavir is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Isavuconazonium: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with isavuconazonium is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and isavuconazonium is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with rifampin is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 and CYP2C8 substrate. Rifampin is a strong CYP3A4 inducer and a moderate inducer of CYP2C8.
    Isoniazid, INH; Rifampin: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with rifampin is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 and CYP2C8 substrate. Rifampin is a strong CYP3A4 inducer and a moderate inducer of CYP2C8.
    Itraconazole: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with itraconazole is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and itraconazole is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Ketoconazole: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with ketoconazole is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. In vitro, coadministration with ketoconazole increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Lapatinib: (Moderate) Monitor for an increase in nab-paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with lapatinib is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and lapatinib is a weak CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8.
    Lefamulin: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with oral lefamulin is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and oral lefamulin is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Leflunomide: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with leflunomide is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and leflunomide is a moderate CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8.
    Lesinurad: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with lesinurad is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer.
    Lesinurad; Allopurinol: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with lesinurad is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer.
    Letermovir: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with letermovir is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates is similar to a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Lopinavir; Ritonavir: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with ritonavir is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors. (Moderate) Monitor for paclitaxel-related adverse reactions during coadministration with lopinavir as concurrent use may increase exposure to paclitaxel. Paclitaxel is a substrate for the transporter organic anion-transporting polypeptide (OATP1B1); lopinavir is an OATP1B1 inhibitor.
    Lorlatinib: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with loraltinib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and loraltinib is a moderate CYP3A4 inducer.
    Lumacaftor; Ivacaftor: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with lumacaftor; ivacaftor is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and lumacaftor is a strong CYP3A4 inducer.
    Lumacaftor; Ivacaftor: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with lumacaftor; ivacaftor is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and lumacaftor is a strong CYP3A4 inducer.
    Mephobarbital: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with mephobarbital is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and mephobarbital is a strong CYP3A4 inducer.
    Methohexital: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with methohexital is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and methohexital is a moderate CYP3A4 inducer.
    Mifepristone: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with mifepristone is necessary due to the risk of increased plasma concentrations of paclitaxel. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. Nab-paclitaxel is a CYP3A4 and CYP2C8 substrate. Mifepristone is a strong CYP3A4 inhibitor and a moderate inhibitor of CYP2C8. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Mitotane: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with mitotane is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and mitotane is a strong CYP3A4 inducer.
    Modafinil: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with modafinil is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and modafinil is a moderate CYP3A4 inducer.
    Nafcillin: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with nafcillin is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and nafcillin is a moderate CYP3A4 inducer.
    Nefazodone: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with nefazodone is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and nefazodone is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Nelfinavir: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with nelfinavir is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and nelfinavir is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Netupitant, Fosnetupitant; Palonosetron: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with netupitant is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and netupitant is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Nevirapine: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with nevirapine is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and nevirapine is a moderate CYP3A4 inducer.
    Nicardipine: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with nicardipine is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and nicardipine is a weak CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8.
    Nilotinib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with nilotinib is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and nilotinib is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with ritonavir is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Omeprazole; Amoxicillin; Rifabutin: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with rifabutin is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and rifabutin is a moderate CYP3A4 inducer.
    Oritavancin: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with oritavancin is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and oritavancin is a weak CYP3A4 inducer.
    Oxcarbazepine: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with oxcarbazepine is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and oxcarbazepine is a weak CYP3A4 inducer.
    Palifermin: (Moderate) Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents.
    Penicillamine: (Major) Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity.
    Pentobarbital: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with pentobarbital is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and pentobarbital is a CYP3A4 inducer.
    Pexidartinib: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with pexidartinib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Phenobarbital: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with phenobarbital is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer.
    Phenytoin: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with phenytoin is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and phenytoin is a strong CYP3A4 inducer.
    Posaconazole: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with posaconazole is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Primidone: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with primidone is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and primidone is a strong CYP3A4 inducer.
    Ribociclib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with ribociclib is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Ribociclib; Letrozole: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with ribociclib is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Rifabutin: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with rifabutin is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and rifabutin is a moderate CYP3A4 inducer.
    Rifampin: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with rifampin is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 and CYP2C8 substrate. Rifampin is a strong CYP3A4 inducer and a moderate inducer of CYP2C8.
    Rifapentine: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with rifapentine is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 and CYP2C8 substrate. Rifapentine is a moderate CYP3A4 and CYP2C8 inducer.
    Rifaximin: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with rifaximin is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate. Rifaximin is a moderate CYP3A4 inducer, although in patients with normal liver function, rifaximin at the recommended dosage regimen is not expected to induce CYP3A4.
    Ritonavir: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with ritonavir is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Saquinavir: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with saquinavir is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and saquinavir is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Secobarbital: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with secobarbital is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and secobarbital is a moderate CYP3A4 inducer.
    Selpercatinib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with selpercatinib is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and selpercatinib is a moderate CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8.
    St. John's Wort, Hypericum perforatum: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with St. John's Wort is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and St. John's Wort is a strong CYP3A4 inducer.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with trimethoprim is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and trimethoprim is a weak CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8.
    Tazemetostat: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with tazemetostat is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and tazemetostat is a weak CYP3A4 inducer.
    Telithromycin: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with telithromycin is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 and CYP2C8 substrate. Telithromycin is a strong CYP3A4 inhibitor and a weak inhibitor of CYP2C8. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was also inhibited by another inhibitor of CYP2C8.
    Telotristat Ethyl: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with telotristat is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and telotristat is a weak CYP3A4 inducer.
    Teriflunomide: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with teriflunomide is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and teriflunomide is a moderate CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8.
    Thiopental: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with thiopental is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and thiopental is a CYP3A4 inducer.
    Tipranavir: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with tipranavir is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and tipranavir is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Trandolapril; Verapamil: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with verapamil is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and verapamil is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Trimethoprim: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with trimethoprim is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and trimethoprim is a weak CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8.
    Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
    Tucatinib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with tucatinib is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Verapamil: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with verapamil is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and verapamil is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Voriconazole: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with voriconazole is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Zanubrutinib: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with zanubrutinib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and zanubrutinib is a weak CYP3A4 inducer.

    PREGNANCY AND LACTATION

    Pregnancy

    Pregnancy should be avoided by females of reproductive potential during nab-paclitaxel treatment and for at least 6 months after the last dose. Although there are no adequately controlled studies in pregnant humans, nab-paclitaxel can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Women who are pregnant or who become pregnant while receiving nab-paclitaxel should be apprised of the potential hazard to the fetus. In animal reproduction studies, administration of nab-paclitaxel to pregnant rats during organogenesis resulted in embryo-fetal toxicity at doses approximately 2% of the maximum recommended human dose (MRHD) on a mg/m2 basis. These toxicities included intrauterine mortality, increased resorptions (up to 5-fold), reduced numbers of litters and live fetuses, reduced fetal body weight, and increased fetal anomalies such as soft tissue and skeletal malformations (e.g. eye bulge, folded retina, microphthalmia, dilation of brain ventricles).

    Due to the potential for serious adverse reactions in nursing infants from nab-paclitaxel, advise women to discontinue breast-feeding during treatment and for 2 weeks after the final dose. It is not known whether nab-paclitaxel is present in human milk, although many drugs are excreted in human milk.

    MECHANISM OF ACTION

    Paclitaxel 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.
     
    Paclitaxel is hydrophobic and must be formulated in a solvent (Cremophohr EL) to increase solubility and bioavailability. Albumin carries water-insoluble molecules in the human body. Nanoparticle albumin-bound (nab) technology improves tumor penetration via albumin receptor-mediated (gp60) endothelial transcytosis.

    PHARMACOKINETICS

    Nab-paclitaxel is administered intravenously. In patients with solid tumors, nab-paclitaxel is extensively protein bound (94%) to plasma proteins and is evenly distributed into blood cells and plasma. In a within-patient comparison study, the fraction of unbound paclitaxel was significantly higher with nab-paclitaxel than with solvent-based paclitaxel (6.2% vs. 2.3%), contributing to significantly higher unbound paclitaxel exposure with nab-paclitaxel compared to solvent-based paclitaxel even when total exposure is comparable. The mean volume of distribution is 1,741 liters, indicating extensive extravascular distribution and/or tissue binding. The volume of distribution is 53% higher for nab-paclitaxel (260 mg/m2 IV over 30 minutes) compared to paclitaxel (175 mg/m2 IV over 3 hours). At 0.31 to 1.15 times the maximum approved recommended dosage, the mean total clearance of paclitaxel ranges from 13 to 30 liters/hour/m2, and the mean terminal elimination half-life ranges from 13 to 27 hours. Clearance was 43% higher for nab-paclitaxel (260 mg/m2 IV over 30 minutes) compared to paclitaxel (175 mg/m2 IV over 3 hours); there were no differences in terminal half-lives. Nab-paclitaxel undergoes extensive nonrenal clearance. After a 30-minute infusion, 4% of a 260 mg/m2 dose of nab-paclitaxel was recovered in the urine as unchanged paclitaxel, with less than 1% as either 6-alpha-hydroxypaclitaxel and 3'-p-hydroxypaclitaxel. Approximately 20% of the total dose is eliminated in the feces.
     
    Affected Cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP2C8, CYP3A4
    Paclitaxel is primarily metabolized via CYP2C8 to 6-alpha-hydroxypaclitaxel in vitro; it also has 2 minor metabolites via CYP3A4 (3'-p-hydroxypaclitaxel and 6-alpha,3'-para-dihydroxypaclitaxel). In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by several agents (i.e., ketoconazole, verapamil, diltiazem, quinidine, dexamethasone, cyclosporine, teniposide, etoposide, and vincristine), but the concentrations exceeded those found in vivo at therapeutic doses; testosterone, 17-alpha-ethinyl estradiol, retinoic acid, and quercetin also inhibited the in vitro formation of 6-alpha hydroxypaclitaxel. Substrates, inhibitors, and inducers of CYP2C8 and/or CYP3A4 may affect the pharmacokinetics of paclitaxel.

    Intravenous Route

    Paclitaxel exhibited linear drug exposure (AUC) across clinical doses ranging from 80 mg/m2 to 300 mg/m2 after IV administration of nab-paclitaxel. In patients with solid tumors, paclitaxel concentrations declined in a biphasic manner after IV administration of nab-paclitaxel, with an initial rapid decline representing distribution to the peripheral compartment and the slower second phase representing drug elimination. The pharmacokinetics of paclitaxel in nab-paclitaxel were independent of the duration of IV infusion.