Nanoparticle albumin-bound (nab) paclitaxel is a microtubule inhibitor that works by assembling and stabilizing microtubules which prevents depolymerization and cell division during mitosis. It is indicated as a single-agent for the treatment of metastatic breast cancer (mBC), in combination with carboplatin for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), and in combination with gemcitabine for the treatment of metastatic adenocarcinoma of the pancreas. The nab-paclitaxel formulation uses nanotechnology to combine human albumin with paclitaxel allowing for the delivery of an insoluble drug in the form of nanoparticles (less than 200 nanometers in diameter). This formulation increases the bioavailability of paclitaxel and results in higher intratumor concentrations. Nab-paclitaxel targets tumors and tumor penetration is facilitated by albumin-receptor (gp60) mediated endothelial transcytosis. This formulation does not require the solvent, Cremophor; therefore, no premedication or special tubing are required with nab-paclitaxel use. Severe neutropenia has been reported and may necessitate an interruption of therapy or dose reduction; new cycles of nab-paclitaxel should not begin until the ANC is 1,500 cells/mm3 or more.
General Administration Information
For storage information, see specific product information within the How Supplied section.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 1
-NIOSH (Draft) 2020 List: Table 1
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
-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.
Emetic Risk
-Low
-Administer routine antiemetic prophylaxis prior to treatment.
Extravasation Risk
-Vesicant
-Administer drug through central line.
Route-Specific Administration
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.
Severe bone marrow suppression, including pancytopenia, has been reported with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) use and is a dose-dependent and dose-limiting toxicity. When administered as monotherapy to patients with advanced breast cancer, neutropenia was reported in 80% (grade 3 or 4, 34%), thrombocytopenia in 2% (grade 3 or 4, less than 1%), and anemia in 33% (grade 3 or 4, 1%) of patients who received nab-paclitaxel in a randomized clinical trial; the frequency of these occurrences were similar to patients treated with paclitaxel. Additionally, febrile neutropenia was reported in 2% of patients, with neutropenic sepsis in less than 1% of nab-paclitaxel patients. The incidence of anemia (all grade, 98%; grade 3 or 4, 28%), thrombocytopenia (all grade, 68%; grade 3 or 4, 18%), and grade 3 or 4 neutropenia (all grade, 85% grade 3 or 4, 47%) were increased when nab-paclitaxel was administered to patients with NSCLC in combination with carboplatin in another clinical trial. Thrombocytopenia (all grade, 74%; grade 3 or 4, 13%) and severe neutropenia (all grade, 73%; grade 3 or 4, 38%) were also reported at higher frequencies when nab-paclitaxel was administered with gemcitabine to patients with advanced pancreatic cancer. Monitor complete blood counts frequently to evaluate patients for myelotoxicity; dose adjustments may be necessary. 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. Bleeding (2%) and epistaxis (7% to 15%) have been reported in the various clinical trials for nab-paclitaxel.
Congestive heart failure was reported in less than 10% of patients with advanced pancreatic cancer treated with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus gemcitabine. Additionally, there have been reports of congestive heart failure and left ventricular dysfunction in postmarketing experience with nab-paclitaxel; most patients were previously exposed to cardiotoxic drugs, such as anthracyclines, or had an underlying cardiac history. In patients with advanced breast cancer treated with nab-paclitaxel or paclitaxel monotherapy, edema occurred in 10% (grade 3 or 4, 0%) versus 8% (grade 3 or 4, less than 1%) of patients, respectively. Peripheral edema occurred in 10% (grade 3 or 4, 0%) of patients with advanced NSCLC treated with nab-paclitaxel plus carboplatin compared with 4% (grade 3 or 4, less than 1%) of patients receiving paclitaxel plus carboplatin. In another clinical trial, peripheral edema was reported in 46% (grade 3 or 4, 3%) of patients with advanced pancreatic cancer treated with nab-paclitaxel plus gemcitabine compared with 30% (grade 3 or 4, 3%) of patients who received gemcitabine alone.
An abnormal ECG (most commonly non-specific repolarization abnormalities, sinus bradycardia, and sinus tachycardia) was reported during treatment with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) monotherapy in 60% of patients with advanced breast cancer, compared with 52% of those who received paclitaxel; the incidence was 35% versus 30% in patients with an abnormal ECG at baseline. ECG abnormalities on study did not usually result in symptoms, were not dose-limiting, and required no intervention. During the 30-minute infusion, hypotension occurred in 5% of patients and bradycardia in less than 1% of patients; these vital sign changes most often caused no symptoms and required neither specific therapy or treatment discontinuation. Severe cardiovascular events possibly related to nab-paclitaxel monotherapy occurred in approximately 3% of patients, including cardiac ischemia/infarction, chest pain (unspecified), cardiac arrest, supraventricular tachycardia (SVT), edema, thrombosis, pulmonary thromboembolism, pulmonary embolism, and hypertension; cases of cerebrovascular attacks (stroke) and transient ischemic attacks have been reported. Hypertension and sinus tachycardia were reported in less than 10% of patients with advanced pancreatic cancer who received nab-paclitaxel and gemcitabine, while atrioventricular block has been reported in postmarketing experience with nab-paclitaxel. In postmarketing reports, most patients with cardiovascular adverse reactions had been previously exposed to cardiotoxic drugs (e.g., anthracyclines), or had an underlying cardiac history.
Pneumonitis, including some cases that were fatal, occurred in 4% of patients with advanced pancreatic cancer treated with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus gemcitabine in a randomized clinical trial compared with 1% of patients who received gemcitabine alone; two of the patients in the nab-paclitaxel arm died (0.5%). In patients with advanced breast cancer, pneumothorax occurred in less than 1% of patients treated with nab-paclitaxel. Cough (7% to 17%) and dyspnea (12%) have been reported in patients treated with nab-paclitaxel as monotherapy or in combination with chemotherapy. There have been postmarketing reports of pneumonitis and interstitial pneumonia in patients receiving nab-paclitaxel, as well as reports of radiation pneumonitis in patients receiving concurrent radiotherapy. Reports of pulmonary fibrosis have been received as part of the continuing surveillance of paclitaxel injection safety and may also be observed with nab-paclitaxel.
Rash was reported in 10% of patients with advanced NSCLC treated with nab-paclitaxel plus carboplatin, and in 30% (grade 3 or 4, 2%) of patients with advanced pancreatic cancer who received nab-paclitaxel plus gemcitabine in separate clinical trials; nail discoloration has also been reported. Maculopapular rash, erythema, pruritus, and scleroderma have been reported in postmarketing experience with nab-paclitaxel, as well as case reports of photosensitivity reactions, radiation recall reaction, and in some patients previously exposed to capecitabine, reports of palmar-plantar erythrodysesthesia (hand and foot syndrome). Stevens-Johnson syndrome and toxic epidermal necrolysis have also been reported.
In a randomized clinical trial of patients with advanced breast cancer treated with nab-paclitaxel monotherapy, alopecia was the most common dermatologic adverse reaction, occurring in 90% of patients treated with nab-paclitaxel compared with 94% of patients who received paclitaxel. Alopecia was reported less frequently in another clinical trial where nab-paclitaxel plus gemcitabine was compared with gemcitabine monotherapy in patients with advanced pancreatic cancer, alopecia (all grade, 50% vs. 5%; grade 3 or 4, 1% vs. 0%).
Injection site reaction occurred in less than 1% of patients treated with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) monotherapy in a randomized clinical trial of patients with advanced breast cancer. In postmarketing surveillance, injection site reactions such as extravasation, phlebitis, cellulitis, induration, tissue necrosis, and fibrosis have been reported in patients who received nab-paclitaxel; some reactions occurred during prolonged infusions or as late as 7 to 10 days after the infusion. Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during administration.
Sensory neuropathy has been reported commonly with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) use and is dose- and schedule-dependent; the frequency and severity may increase with cumulative doses. Peripheral neuropathy occurred in 71% (grade 3, 10%) of metastatic breast cancer patients who received nab-paclitaxel monotherapy compared with 56% (grade 3 or higher, 2%) of patients treated with paclitaxel in a randomized clinical trial; over half of the nab-paclitaxel patients with severe neuropathy (58%) improved after a median of 22 days. One incident of grade 2 motor neuropathy was observed. Peripheral neuropathy occurred in 48% to 54% (grade 3, 3% to 17%) of patients treated with nab-paclitaxel in combination with either carboplatin or gemcitabine in separate clinical trials; grade 3 neuropathy improved to grade 1 or less in 59% of patients who received nab-paclitaxel plus carboplatin. When administered in combination with gemcitabine, the median time to onset of peripheral neuropathy was 140 days and the median time to improvement (grade 1 or less) was 29 days. Additional neurologic adverse reactions include dysgeusia when administered in combination with gemcitabine (grade 1 or 2, 16%), as well as cranial nerve palsies and vocal cord paresis in postmarketing experience. Autonomic neuropathy resulting in paralytic ileus was also reported in postmarketing experience with nab-paclitaxel.
Myalgia/arthralgia (all grade, 44% vs. 49%; grade 3 or 4, 8% vs. 4%) occurred in less frequently in metastatic breast cancer patients who received nanoparticle albumin-bound paclitaxel (nab-paclitaxel) monotherapy compared with paclitaxel in a randomized clinical trial; symptoms typically occurred within 2 to 3 days of nab-paclitaxel therapy, were transient, and resolved within a few days. When nab-paclitaxel was administered in combination with carboplatin or gemcitabine in separate clinical trials, arthralgia occurred in 11% to 13% of patients (grade 3 or 4, less than or equal to 1%) and myalgia in 10% (grade 3 or 4, less than or equal to 1%) of patients. Fatigue (all grade, 59%; grade 3 or 4, 18%) and asthenia (all grade, 19%; grade 3 or 4, 7%) were additionally reported in patients with advanced pancreatic cancer who received nab-paclitaxel plus gemcitabine.
In a randomized clinical trial, the incidence of gastrointestinal adverse reactions in patients with advanced breast cancer treated with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) monotherapy were slightly higher than in patients who received paclitaxel monotherapy, including nausea (all grade, 30% vs 22%; grade 3 or higher, 3% vs. less than 1%), vomiting (all grade, 18% vs. 10%; grade 3 or 4, 4% vs. 1%), diarrhea (all grade, 27% vs. 15%; grade 3 or 4, less than 1% vs. 1%), and mucositis/stomatitis (all grade, 7% vs. 6%; grade 3 or 4, less than 1% vs. 0%); dehydration was also reported. In general, the incidence of gastrointestinal adverse reactions was similar in a different clinical trial of advanced lung cancer patients treated with nab-paclitaxel plus carboplatin, including nausea (27%), anorexia (17%), constipation (16%), diarrhea (15%), and vomiting (12%). Gastrointestinal effects were more frequent in combination with gemcitabine, including nausea (all grade, 54%; grade 3 or 4, 6%), diarrhea (all grade, 44%; grade 3 or 4, 6%), vomiting (all grade, 36%; grade 3 or 4, 6%), anorexia (all grade, 36%; grade 3 or 4, 5%), dehydration (all grade, 21%; grade 3 or 4, 7%), and mucositis (all grade, 10%; grade 3 or 4, 1%). Diarrhea, dehydration, and anorexia occurred more frequently in patients 65 years old or older compared with younger patients. Other GI adverse reactions reported in postmarketing surveillance of nab-paclitaxel include GI obstruction, GI perforation, pancreatitis, and ischemic colitis. Neutropenic enterocolitis (typhlitis) has been reported rarely with paclitaxel injection alone and in combination with other chemotherapeutic agents, despite the use of granulocyte colony-stimulating factors.
Reports in the literature of abnormal visual evoked potentials in patients treated with paclitaxel injection suggest persistent optic nerve damage; these may also be observed with nanoparticle albumin-bound paclitaxel (nab-paclitaxel). Ocular/visual disturbances occurred in 13% of patients with advanced breast cancer treated with nab-paclitaxel monotherapy. Severe cases of visual impairment (e.g., keratitis, blurred vision) occurred in 1% of patients, typically in those who received higher doses than those recommended (300 or 375 mg/m2); these effects generally have been reversible. Reduced visual acuity due to cystoid macular edema (CME) has been reported during treatment with nab-paclitaxel in postmarketing experience, as well as with other taxanes; CMS occurred in less than 10% of patients with advanced pancreatic cancer treated with nab-paclitaxel plus gemcitabine. After cessation of treatment, CME improves and visual acuity may return to baseline. Conjunctivitis and increased lacrimation have also been reported with paclitaxel injection.
Reports of hepatic necrosis and hepatic encephalopathy leading to death have been received as part of the continuing surveillance of paclitaxel injection safety and may occur following nanoparticle albumin-bound paclitaxel (nab-paclitaxel) treatment. In patients with advanced breast cancer, hyperbilirubinemia occurred with the same frequency in patients treated with nab-paclitaxel monotherapy compared with paclitaxel monotherapy (7% vs. 7%). The incidence of elevated alkaline phosphatase (36% vs. 31%), increased AST (elevated hepatic enzymes) (39% vs. 32%), and grade 3 or 4 increases in GGT (14% vs. 10%) were slightly higher in the nab-paclitaxel arm.
Infection occurred in 24% of patients with advanced breast cancer treated with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) monotherapy compared with 20% who received paclitaxel; oral candidiasis, respiratory tract infections, and pneumonia were the most frequently reported infections. Fever occurred in 41% (grade 3 or 4, 3%) of patients with advanced pancreatic cancer treated with nab-paclitaxel plus gemcitabine compared with 28% (grade 3 or 4, 1%) of those receiving gemcitabine alone; it was also reported in patients receiving nab-paclitaxel monotherapy. Urinary tract infections, including cystitis and urosepsis, occurred in 11% (grade 3 or 4, 2%) of patients in the nab-paclitaxel arm, while oral candidiasis and pneumonia were each reported in less than 10%. Sepsis occurred in 5% of patients who received nab-paclitaxel plus gemcitabine compared with 2% treated with gemcitabine alone, regardless of the presence or absence of neutropenia. Risk factors for sepsis included biliary obstruction or presence of biliary stent.
Headache (all grade, 14% vs. 9%; grade 3 or 4, less than 1% vs. less than 1%), depression (all grade, 12% vs. 6%; grade 3 or 4, less than 1% vs. 0%), and pain in extremities (all grade, 11% vs. 6%; grade 3 or 4, 1% vs. 1%) occurred more often in patients with advanced pancreatic cancer treated with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus gemcitabine compared with gemcitabine alone in a randomized clinical trial.
Hypokalemia was reported in 12% of patients (grade 3 or 4, 4%) with metastatic adenocarcinoma of the pancreas treated with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus gemcitabine compared wtih 7% (grade 3 or 4, 1%) of those who received gemcitabine alone in a multinational, randomized, open-label trial.
Tumor lysis syndrome (TLS) has been reported in postmarketing experience with nanoparticle albumin-bound paclitaxel (nab-paclitaxel).
Overall, 11% of patients with advanced breast cancer treated with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) monotherapy experienced serum creatinine elevation, with a 1% incidence of severe renal dysfunction (renal failure (unspecified)).
Severe and sometimes fatal hypersensitivity reactions, including anaphylactic/anaphylactoid reactions, have been reported with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) therapy. In a randomized clinical trial of patients with advanced breast cancer, 4% of patients treated with nab-paclitaxel experienced hypersensitivity compared with 12% who received paclitaxel; severe reactions were reported in 0% versus 2% of patients, respectively. Symptoms of hypersensitivity occurring on the day of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) administration included dyspnea (1%), flushing (less than 1%), hypotension (less than 1%), chest pain (less than 1%), and arrhythmia (less than 1%). In postmarketing experience, cross-hypersensitivity between nab-paclitaxel and other taxanes has been reported.
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 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 (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 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.
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.
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.
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.
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.
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).
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.
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 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).
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.
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.
For the treatment of breast cancer:
-for the neoadjuvant treatment of hormone receptor (HR)-negative, HER2-negative (triple-negative) breast cancer, in combination with atezolizumab and sequentially followed by cyclophosphamide plus doxorubicin (dose-dense AC) plus atezolizumab*:
Intravenous dosage:
Adults: 125 mg/m2 once weekly in combination with atezolizumab (840 mg IV every 2 weeks) for 12 weeks, followed by atezolizumab 840 mg IV every 2 weeks in combination with doxorubicin (60 mg/m2 IV) plus cyclophosphamide (600 mg/m2 IV) every 2 weeks for 8 weeks (dose-dense AC), followed by surgery. After surgery, continue atezolizumab 1,200 mg IV every 3 weeks for 11 cycles to complete approximately 12 months of atezolizumab therapy. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a randomized, phase 3 clinical trial (IMpassion031), neoadjuvant treatment with atezolizumab plus sequential nab-paclitaxel and AC chemotherapy significantly improved pCR compared with neoadjuvant placebo plus sequential nab-paclitaxel and AC chemotherapy in patients with early TNBC, regardless of PD-L1 status.
-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 increased the risk of death compared with placebo and paclitaxel in the PD-L1-positive population.
NOTE: Atezolizumab is FDA-approved for this indication in combination with nab-paclitaxel.
Intravenous dosage:
Adults: 100 mg/m2 IV on days 1, 8, and 15, every 28 days until disease progression or unacceptable toxicity. Administer in combination with atezolizumab 840 mg IV every 2 weeks; OR 1,200 mg IV every 3 weeks; OR 1,680 mg IV every 4 weeks until disease progression or unacceptable toxicity. Administer atezolizumab prior to nab-paclitaxel when given on the same day. Atezolizumab and nab-paclitaxel may be discontinued independently of each other. 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 (IMpassion130). In the subgroup of patients with PD-L1 expression of 1% or more, PFS was 7.4 months in the atezolizumab arm compared with 4.8 months in the placebo arm; the objective response rate was 53% versus 33% for a median duration of 9.2 months versus 6.2 months, respectively. 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 locally recurrent unresectable or metastatic, PD-L1 positive (CPS 10 or more), triple negative breast cancer (TNBC), in combination with pembrolizumab*:
NOTE: Select patients for treatment based on the presence of positive PD-L1 expression. Information on FDA-approved tests for the detection of PD-L1 expression in TNBC is available at http://www.fda.gov/CompanionDiagnostics.
NOTE: Pembrolizumab is FDA-approved in combination with carboplatin and gemcitabine for this indication.
Intravenous dosage:
Adults: 100 mg/m2 on days 1, 8, and 15, every 28 days in combination with pembrolizumab (200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression); the number of cycles of nab-paclitaxel was not specified. In a multicenter, double-blind clinical trial (KEYNOTE-355), patients with locally recurrent unresectable or metastatic TNBC who had not been previously treated with chemotherapy in the metastatic setting were randomized to treatment with either pembrolizumab or placebo in combination with paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin regardless of tumor PD-L1 expression. The addition of pembrolizumab to chemotherapy significantly improved the median progression-free survival (9.7 months vs. 5.6 months) compared with placebo plus chemotherapy in the subgroup of patients with a CPS of 10 or more. The objective response rate was 53% compared with 40%, respectively (complete response, 17% vs. 13%) for a median duration of 19.3 months in the pembrolizumab arm and 7.3 months in the placebo arm.
-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 3 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). The TTP was significantly longer in patients treated with nab-paclitaxel as second line or greater (20.9 weeks vs. 16.1 weeks) 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).
-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 2, 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 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 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. In a multicenter, randomized, double-blind clinical trial (KEYNOTE-407), treatment with pembrolizumab plus carboplatin and either paclitaxel or nab-paclitaxel (n = 278) significantly improved median overall survival (17.1 months vs. 11.6 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 on days 1, 8, and 15, every 3 weeks for a maximum of 4 to 6 cycles. Administer in combination with carboplatin (AUC 6 IV on day 1 every 3 weeks for up to 4 to 6 cycles) and atezolizumab (840 mg IV every 2 weeks; OR 1,200 mg IV every 3 weeks; OR 1,680 mg IV every 4 weeks until disease progression or unacceptable toxicity). Administer atezolizumab prior to chemotherapy when given on the same day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. 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.
Therapeutic Drug Monitoring:
Dosage Adjustments for Treatment-Related Toxicities
Metastatic Breast Cancer
Hematologic: Do not begin a new cycle of every-3-week nab-paclitaxel until the ANC is at least 1,500 cells/mm3 and platelets are at least 100,000 cells/mm3.
Neutropenia
-Severe prolonged neutropenia (ANC less than 500 cells/mm3 for 7 days or more): Hold nab-paclitaxel therapy. When the ANC recovers to greater than 1,500 cells/mm3 and platelets are greater than 100,000 cells/mm3, resume therapy at a reduced nab-paclitaxel dose of 220 mg/m2. If severe neutropenia recurs, further reduce the dose of nab-paclitaxel to 180 mg/m2 upon neutrophil recovery.
Neuropathy
-Grade 3 or 4 sensory neuropathy: Hold nab-paclitaxel therapy. When neuropathy resolves to grade 1 or 2, resume therapy at a reduced nab-paclitaxel dose of 220 mg/m2. If grade 3 or higher sensory neuropathy recurs, further reduce the dose of nab-paclitaxel to 180 mg/m2 upon recovery to grade 1 or 2 neuropathy.
Non-Small Cell Lung Cancer (NSCLC), in combination with carboplatin
Hematologic: Do not administer nab-paclitaxel unless the ANC is at least 1,500 cells/mm3 on Day 1 or at least 500 cells/mm3 on Days 8 or 15, and the platelet count is at least 100,000 cells/mm3 on Day 1 or at least 50,000 cells/mm3 on Days 8 or 15.
Neutropenia
-Prolonged Neutropenia: If Day 1 chemotherapy is delayed by more than 7 days due to an ANC of less than 1,500 cells/mm3, initially reduce the weekly dose of nab-paclitaxel to 75 mg/m2 and reduce the dose of every-3-week carboplatin to an AUC of 4. If a delay of more than 7 days due to neutropenia recurs, further reduce the weekly dose of nab-paclitaxel to 50 mg/m2 and reduce the dose of every-3-week carboplatin to an AUC of 3. For the third occurrence of prolonged neutropenia, discontinue treatment.
-Severe prolonged neutropenia (ANC less than 500 cells/mm3 for 7 days or more): Do not administer nab-paclitaxel. If the ANC is less than 500 cells/mm3 for more than 7 days, initially reduce the weekly dose of nab-paclitaxel to 75 mg/m2 and reduce the dose of every-3-week carboplatin to an AUC of 4. If a delay of more than 7 days due to neutropenia recurs, further reduce the weekly dose of nab-paclitaxel to 50 mg/m2 and reduce the dose of every-3-week carboplatin to an AUC of 3. For the third occurrence of prolonged neutropenia, discontinue treatment.
Neutropenic Fever (ANC less than 500 cells/mm3 with fever greater than 38 degrees C)
-After the first occurrence of neutropenic fever, reduce the weekly dose of nab-paclitaxel to 75 mg/m2 and reduce the dose of every-3-week carboplatin to an AUC of 4. If neutropenic fever recurs, further reduce the weekly dose of nab-paclitaxel to 50 mg/m2 and reduce the dose of every-3-week carboplatin to an AUC of 3. For the third occurrence of neutropenic fever, discontinue treatment.
Thrombocytopenia
-Severe thrombocytopenia (platelet counts less than 50,000 cells/mm3): Do not administer nab-paclitaxel. If the platelet count decreases to less than 50,000 cells/mm3, initially reduce the weekly dose of nab-paclitaxel to 75 mg/m2 and reduce the dose of every-3-week carboplatin to an AUC of 4.5. If the platelet count decreases to less than 50,000 cells/mm3 again, discontinue treatment.
Neuropathy
-Grade 3 or 4 sensory neuropathy: Hold nab-paclitaxel therapy. When neuropathy resolves to grade 1 or less, initially resume therapy at a reduced weekly nab-paclitaxel dose of 75 mg/m2; also reduce the dose of every-3-week carboplatin to an AUC of 4.5. If grade 3 or 4 sensory neuropathy recurs, further reduce the weekly dose of nab-paclitaxel to 50 mg/m2 and every-3-week carboplatin dose to an AUC of 3 upon recovery to grade 1 or less. Discontinue treatment if grade 3 or 4 sensory neuropathy occurs for the third time.
Pancreatic Adenocarcinoma, in combination with gemcitabine
Cutaneous toxicity
-Grade 2 or 3: Reduce the dose of nab-paclitaxel (125 mg/m2 to 100 mg/m2; 100 mg/m2 to 75 mg/m2) and gemcitabine (1,000 mg/m2 to 800 mg/m2; 800 mg/m2 to 600 mg/m2) by one dose level; if additional dose reductions are required, discontinue therapy. If cutaneous toxicity persists, discontinue treatment.
Gastrointestinal toxicity
-Grade 3 mucositis or diarrhea: Hold both nab-paclitaxel and gemcitabine. When symptoms resolve to grade 1 or less, resume therapy at a reduced dose of nab-paclitaxel (125 mg/m2 to 100 mg/m2; 100 mg/m2 to 75 mg/m2) and gemcitabine (1,000 mg/m2 to 800 mg/m2; 800 mg/m2 to 600 mg/m2); if additional dose reductions are required, discontinue therapy.
Hematologic: Do not administer nab-paclitaxel or gemcitabine unless the ANC is at least 1,500 cells/mm3 on Day 1 or at least 500 cells/mm3 on Days 8 or 15, and the platelet count is at least 100,000 cells/mm3 on Day 1 or at least 50,000 cells/mm3 on Days 8 or 15.
Neutropenia, Day 1
-Do not administer nab-paclitaxel or gemcitabine unless the ANC is at least 1,500 cells/mm3 on Day 1.
Neutropenia, Day 8
-ANC 500 to 999 cells/mm3: Reduce the dose of nab-paclitaxel (125 mg/m2 to 100 mg/m2; 100 mg/m2 to 75 mg/m2) and gemcitabine (1,000 mg/m2 to 800 mg/m2; 800 mg/m2 to 600 mg/m2) by one dose level from Day 1; if additional dose reductions are required, discontinue therapy.
-ANC less than 500 cells/mm3: Hold both nab-paclitaxel and gemcitabine.
Neutropenia, Day 15
-ANC 1,000 cells/mm3 or more: If the Day 8 doses were administered (either at a reduced dose or without modification), continue therapy at Day 8 doses. If Day 8 doses were withheld, restart therapy at a reduced dose of nab-paclitaxel (125 mg/m2 to 100 mg/m2; 100 mg/m2 to 75 mg/m2) and gemcitabine (1,000 mg/m2 to 800 mg/m2; 800 mg/m2 to 600 mg/m2) by one dose level from Day 1. If additional dose reductions are required, discontinue therapy.
-ANC 500 to 999 cells/mm3: If the Day 8 doses were administered (either at a reduced dose or without modification), reduce the dose of nab-paclitaxel (125 mg/m2 to 100 mg/m2; 100 mg/m2 to 75 mg/m2) and gemcitabine (1,000 mg/m2 to 800 mg/m2; 800 mg/m2 to 600 mg/m2) by one dose level from Day 8; if additional dose reductions are required, discontinue therapy. If Day 8 doses were withheld, restart therapy at a reduced dose of nab-paclitaxel (125 mg/m2 to 75 mg/m2) and gemcitabine (1,000 mg/m2 to 600 mg/m2) by 2 dose levels from Day 1; discontinue therapy if the dose of nab-paclitaxel on Day 8 was 100 mg/m2 and the dose of gemcitabine was 800 mg/m2.
-ANC less than 500 cells/mm3: Hold both nab-paclitaxel and gemcitabine.
Neutropenic fever
-Grade 3 or 4: Hold both nab-paclitaxel and gemcitabine. When the fever resolves and ANC is 1,500 cells/mm3 or more, resume therapy at a reduced dose of nab-paclitaxel (125 mg/m2 to 100 mg/m2; 100 mg/m2 to 75 mg/m2) and gemcitabine (1,000 mg/m2 to 800 mg/m2; 800 mg/m2 to 600 mg/m2). If additional dose reductions are required, discontinue therapy.
Thrombocytopenia, Day 1
-Do not administer nab-paclitaxel or gemcitabine unless the platelet count is at least 100,000 cells/mm3 on Day 1.
Thrombocytopenia, Day 8
-Platelets 50,000 to 74,999 cells/mm3: Reduce the dose of nab-paclitaxel (125 mg/m2 to 100 mg/m2; 100 mg/m2 to 75 mg/m2) and gemcitabine (1,000 mg/m2 to 800 mg/m2; 800 mg/m2 to 600 mg/m2) by one dose level from Day 1; if additional dose reductions are required, discontinue therapy.
-Platelets less than 50,000 cells/mm3: Hold both nab-paclitaxel and gemcitabine.
Thrombocytopenia, Day 15
-Platelets 75,000 cells/mm3 or more: If the Day 8 doses were administered (either at a reduced dose or without modification), continue therapy at Day 8 doses. If Day 8 doses were withheld, restart therapy at a reduced dose of nab-paclitaxel (125 mg/m2 to 100 mg/m2; 100 mg/m2 to 75 mg/m2) and gemcitabine (1,000 mg/m2 to 800 mg/m2; 800 mg/m2 to 600 mg/m2) by one dose level from Day 1. If additional dose reductions are required, discontinue therapy.
-Platelets 50,000 to 74,999 cells/mm3: If the Day 8 doses were administered (either at a reduced dose or without modification), reduce the dose of nab-paclitaxel (125 mg/m2 to 100 mg/m2; 100 mg/m2 to 75 mg/m2) and gemcitabine (1,000 mg/m2 to 800 mg/m2; 800 mg/m2 to 600 mg/m2) by one dose level from Day 8; if additional dose reductions are required, discontinue therapy. If Day 8 doses were withheld, restart therapy at a reduced dose of nab-paclitaxel (125 mg/m2 to 75 mg/m2) and gemcitabine (1,000 mg/m2 to 600 mg/m2) by 2 dose levels from Day 1; discontinue therapy if the dose of nab-paclitaxel on Day 8 was 100 mg/m2 and the dose of gemcitabine was 800 mg/m2.
-Platelets less than 50,000 cells/mm3: Hold both nab-paclitaxel and gemcitabine.
Peripheral neuropathy
-Grade 3 or 4: Hold nab-paclitaxel; when peripheral neuropathy resolves to grade 1 or less, resume therapy at a reduced dose of nab-paclitaxel (125 mg/m2 to 100 mg/m2; 100 mg/m2 to 75 mg/m2); if additional dose reductions are required, discontinue therapy. No dose reduction of gemcitabine is necessary.
Maximum Dosage Limits:
-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.
Patients with Hepatic Impairment Dosing
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.
Patients with Renal Impairment Dosing
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.
*non-FDA-approved indication
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.
Adagrasib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with adagrasib is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor. In vitro, coadministration with both strong and moderate CYP3A 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 CYP3A 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; 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.
Asciminib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of asciminib is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and asciminib is a weak CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8.
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.
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.
Belzutifan: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with belzutifan is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A substrate and belzutifan is a weak CYP3A inducer.
Berotralstat: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with berotralstat is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and berotralstat 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.
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 weak CYP3A4 inducer.
Butalbital; Acetaminophen: (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.
Butalbital; Acetaminophen; 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.
Butalbital; Acetaminophen; 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.
Butalbital; Aspirin; 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.
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 CYP3A and CYP2C8 substrate and carbamazepine is a strong CYP3A inducer and a CYP2C8 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.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
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 moderate 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. Nab-paclitaxel is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor. In vitro, coadministration with moderate CYP3A 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 CYP3A 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.
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.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Dexamethasone: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with dexamethasone is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A substrate and dexamethasone is a weak CYP3A inducer.
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 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.
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.
Enasidenib: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with enasidenib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A substrate and enasidenib is a weak CYP3A inducer.
Encorafenib: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with encorafenib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A substrate and encorafenib is a strong CYP3A inducer.
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.
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.
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 CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. In vitro, coadministration with both strong and moderate CYP3A 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 CYP3A 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.
Glycerol Phenylbutyrate: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with glycerol phenylbutyrate is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A substrate and glycerol phenylbutyrate is a weak CYP3A inducer.
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.
Lansoprazole; Amoxicillin; 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.
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.
Lenacapavir: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with lenacapavir is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor. In vitro, coadministration with both strong and moderate CYP3A 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 CYP3A inhibitors.
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.
Levoketoconazole: (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.
Lonafarnib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with lonafarnib is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and lonafarnib 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.
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.
Mavacamten: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with mavacamten is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Meropenem: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with meropenem is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 and CYP3A substrate and meropenem is a weak CYP2C8 and weak CYP3A inducer.
Meropenem; Vaborbactam: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with meropenem is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 and CYP3A substrate and meropenem is a weak CYP2C8 and weak CYP3A 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.
Mitapivat: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with mitapivat is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A substrate and mitapivat is a weak CYP3A inducer.
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.
Mobocertinib: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with mobocertinib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and mobocertinib is a weak CYP3A 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 CYP3A substrate and nevirapine is a weak CYP3A 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.
Niraparib; 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.
Nirmatrelvir; 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.
Nirogacestat: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with nirogacestat is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A substrate and nirogacestat is a moderate CYP3A inhibitor. In vitro, coadministration with both strong and moderate CYP3A 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 CYP3A inhibitors.
Odevixibat: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with odevixibat is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A substrate and odevixibat is a weak CYP3A inducer.
Olanzapine; 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.
Olutasidenib: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with olutasidenib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A substrate and olutasidenib is a weak CYP3A inducer.
Omaveloxolone: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with omaveloxolone is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A and CYP2C8 substrate and omaveloxolone is a weak CYP3A and CYP2C8 inducer.
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.
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.
Phenobarbital; Hyoscyamine; Atropine; 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.
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.
Pirtobrutinib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with pirtobrutinib is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and pirtobrutinib is a moderate CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8.
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.
Repotrectinib: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with repotrectinib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A substrate and repotrectinib is a moderate CYP3A inducer.
Resmetirom: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with resmetirom is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and resmetirom is a weak CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8.
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 substrate and rifapentine is a strong CYP3A4 inducer.
Ritlecitinib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with ritlecitinib is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor. In vitro, coadministration with both strong and moderate CYP3A 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 CYP3A inhibitors.
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.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
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.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Monitor for decreased efficacy and/or increased paclitaxel-related adverse reactions if coadministration with taurursodiol is necessary. Concomitant use may alter nab-paclitaxel exposure. Paclitaxel is a CYP3A and CYP2C8 substrate and taurursodiol is a weak CYP3A inducer and CYP2C8 inhibitor. The net effect on paclitaxel exposure is unknown.
Sotorasib: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with sotorasib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and sotorasib is a moderate CYP3A4 inducer.
Spironolactone: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with spironolactone is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and spironolactone is a weak CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with spironolactone is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate and spironolactone is a weak 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.
Stiripentol: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions or decreased efficacy of nab-paclitaxel if coadministration of nab-paclitaxel with stiripentol is necessary due to the risk of altered plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate. Stiripentol is a weak CYP2C8 inhibitor, as well as being both an inhibitor and inducer of CYP3A4. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by inhibitors of CYP3A4 and CYP2C8.
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.
Tecovirimat: (Moderate) Monitor for decreased efficacy of nab-paclitaxel or an increase in paclitaxel-related adverse reactions if coadministration with tecovirimat is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 and CYP2C8 substrate. Tecovirimat is a weak CYP3A4 inducer and a weak CYP2C8 inhibitor.
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.
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.
Vonoprazan; Amoxicillin; 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.
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.
Voxelotor: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with voxelotor is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor. In vitro, coadministration with both strong and moderate CYP3A 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 CYP3A 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.
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.
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.
-Route-Specific Pharmacokinetics
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.
-Special Populations
Hepatic Impairment
Mild hepatic impairment (total bilirubin 1.5 times the upper limit of normal [ULN] or less and AST 10 times ULN or less) did not have a clinically meaningful effect on the pharmacokinetics of paclitaxel in nab-paclitaxel. Patients with moderate (total bilirubin 1.6 to 3 times ULN and AST 10 times ULN or less) to severe (total bilirubin 3.1 to 5 times ULN) hepatic impairment had a 22% to 26% decrease in the maximum elimination rate of paclitaxel and approximately 20% increase in mean paclitaxel AUC compared with patients with normal hepatic function.
Renal Impairment
Mild to moderate renal impairment (CrCl 30 to 89 mL/min) did not have a clinically meaningful effect on the pharmacokinetics of paclitaxel in nab-paclitaxel. The effect of severe renal impairment or end stage renal disease (CrCl less than 30 mL/min) on the pharmacokinetics of paclitaxel in nab-paclitaxel is unknown.
Pediatrics
The safety and effectiveness of nab-paclitaxel in pediatric patients have not been established. The maximum tolerated dose (MTD) for body surface area (BSA) was lower in pediatric patients with recurrent or refractory solid tumors (n = 96; age 1.4 to 16 years) compared to adults in an open-label, dose-escalation, dose-expansion study; no new safety signals were observed. Nab-paclitaxel exposures normalized by dose were also higher in these pediatric patients compared to adults.
Geriatric
Age (24 to 85 years) did not have a clinically meaningful effect on the pharmacokinetics of paclitaxel in nab-paclitaxel.
Gender Differences
Gender did not have a clinically meaningful effect on the pharmacokinetics of paclitaxel in nab-paclitaxel.
Ethnic Differences
Ethnicity (Asian vs. Caucasian) did not have a clinically meaningful effect on the pharmacokinetics of paclitaxel in nab-paclitaxel.
Obesity
Body weight (40 kg to 143 kg) and body surface area (1.3 m2 to 2.4 m2) did not have a clinically meaningful effect on the pharmacokinetics of paclitaxel in nab-paclitaxel.
Other
The type of solid tumor did not have a clinically meaningful effect on the pharmacokinetics of paclitaxel in nab-paclitaxel.