CONTRAINDICATIONS / PRECAUTIONS
Polyoxyethylated castor oil hypersensitivity, serious hypersensitivity reactions or anaphylaxis, taxane hypersensitivity
Paclitaxel is contraindicated in patients who have a history of severe paclitaxel hypersensitivity; those patients with a history of other taxane hypersensitivity should be given paclitaxel with caution. A risk of serious hypersensitivity reactions or anaphylaxis has been reported in patients receiving paclitaxel. Patients with known polyoxyethylated castor oil hypersensitivity should not receive the Taxol formulation or should receive it cautiously and with premedication. Polyoxyethylated compound (Cremophor EL) is believed to be responsible for anaphylactoid reactions. Severe hypersensitivity reactions (e.g., acute bronchospasm and/or hypotension) have occurred despite antihistamine (H1- and H2-blockers) and corticosteroid premedication. Hypersensitivity reactions may occur within minutes of beginning an infusion. Severe may reactions necessitate the immediate discontinuation of the infusion. Patients should be monitored closely.
Bone marrow suppression, herpes infection, infection, Kaposi's sarcoma, neutropenia, requires a specialized care setting, requires an experienced clinician, thrombocytopenia, varicella, viral infection
Paclitaxel is associated with dose-related bone marrow suppression. It should not be given to patients with severe thrombocytopenia or neutropenia, with solid tumors who have baseline neutrophil counts of less than 1,500 cells/mm3, with AIDS-related Kaposi's sarcoma, or with baseline neutrophil count is less than 1000 cells/mm3; these patients may have more frequent and severe hematologic toxicities, infections (including opportunistic infections), and febrile neutropenia compared to patients with solid tumors. In all patients, blood counts should be monitored frequently during treatment. Generally, the next cycle should not be given until neutrophils reach 1500/mm3 and higher (1000/mm3 for Kaposi's sarcoma patients) and platelets recover to 100,000/mm3 or higher. In patients with a neutrophil count of less than 500 cells/mm3 for longer than 1 week, consider adding colony-stimulating factor support or reducing subsequent paclitaxel doses by 20%. Due to these severe adverse reactions, paclitaxel requires an experienced clinician knowledgeable in the use of cancer chemotherapeutic agents. Administration requires a specialized care setting such as a hospital or treatment facility so that facilities are readily available for appropriate management of complications. Use cautiously in patients who have myelosuppression due to previous therapy such as other chemotherapy or radiotherapy; these patients may be more susceptible to the myelosuppressive effects of paclitaxel. Patients with active infection should be treated prior to receiving paclitaxel. Patients with a history of varicella zoster, other herpes infection (e.g., herpes simplex), or other viral infection are at risk for reactivation of the infection when treated with chemotherapy.
Angina, AV block, bradycardia, cardiac arrhythmias, cardiac disease, heart failure, myocardial infarction
Severe conduction abnormalities have been documented in during paclitaxel therapy and in some cases requiring pacemaker placement. If patients develop significant cardiac conduction abnormalities during paclitaxel infusion, appropriate therapy should be administered and continuous cardiac monitoring should be performed during subsequent therapy with paclitaxel. Patients with cardiac disease including angina, cardiac arrhythmias including AV block, history of congestive heart failure, or myocardial infarction within the past 6 months should be carefully monitored during paclitaxel therapy due to the potential for serious cardiac complications. In addition, patients receiving paclitaxel in combination with doxorubicin for metastatic breast cancer should be considered for cardiac monitoring. In a review of gynecologic cancer patients with major risk factors who received paclitaxel, no evidence of additive adverse effects was noted. As many of the reports of severe cardiac events were seen in early trials of paclitaxel as a result of hypersensitivity reactions, appropriate premedication appears to have decreased the incidence of these effects. It should be noted that patients with severe conduction abnormalities were not included in this review. Because bradycardia is a common adverse reaction, patients receiving drugs known to cause bradycardia, such as beta-blockers, calcium-channel blockers, and digoxin, also should be monitored carefully.
Peripheral neuropathy
Preexisting peripheral neuropathy is not a contraindication for paclitaxel; although, these patients may be at increased risk to develop paclitaxel-induced neurotoxicity. Exacerbation of pre-existing neuropathies may occur at relatively low paclitaxel doses. Patients who have been exposed to agents that may cause neurotoxicity, such as cisplatin, may also be at increased risk for paclitaxel-induced neurotoxicity. Patients with severe neurotoxic symptoms should have their paclitaxel doses reduced by 20%.
Geriatric
Geriatric patients are at increased risk for adverse reactions to paclitaxel therapy. In most studies, severe myelosuppression was more frequent in elderly patients; in some studies, severe neuropathy was more common in the elderly. In two clinical studies of non-small cell lung cancer (NSCLC), the elderly patients treated with paclitaxel had a higher incidence of cardiovascular events.
Hepatic disease
Paclitaxel should be used cautiously in patients with known hepatic disease. Because paclitaxel is extensively metabolized through cytochrome P-450 system, excessive toxicity may occur in patients with hyperbilirubinemia and elevated liver enzymes. Limited data suggest myelotoxicity may be increased in patients with serum bilirubin > 2 times ULN. Patients with hepatic disease may require dose reductions (see Dosage).
Pregnancy
Paclitaxel is classified as FDA pregnancy risk category D and has been shown to produce toxic effects, including death, in fetal animal studies. There are no data concerning the effects in pregnant women. Therefore, paclitaxel should be avoided during pregnancy, and females of childbearing potential should be instructed to avoid becoming pregnant during paclitaxel therapy. If a women becomes pregnant while receiving this drug, she should be counseled of the potential harm to the fetus and the possibility of loss of pregnancy.
Breast-feeding
It is unknown whether paclitaxel is excreted into human breast milk; paclitaxel was excreted into the breast milk of lactating rats at concentrations higher than those seen in plasma. Because of the potential for serious adverse reactions in nursing infants, patients should be instructed to discontinue breast-feeding during paclitaxel therapy.
Radiation therapy
Patients who have received prior radiation therapy are at risk for radiation recall reactions when receiving paclitaxel. These patients should be monitored closely. In addition, paclitaxel may increase the efficacy and/or the adverse reactions of radiation therapy.
Intramuscular injections
Intramuscular injections should be avoided in patients with platelet counts < 50,000/mm3 who are receiving paclitaxel. IM injections can cause bleeding, bruising, or hematomas in patients with paclitaxel-induced thrombocytopenia.
Dental disease, dental work
Myelosuppressive effects of paclitaxel can increase the risk of infection or bleeding; therefore, dental work should be delayed until blood counts have returned to normal. Patients, especially those with dental disease, should be instructed in proper oral hygiene, including caution in use of regular toothbrushes, dental floss, and toothpicks.
Alcoholism, driving or operating machinery
The Taxol formulation of paclitaxel contains a high concentration of ethanol (49.7% (v/v)). Consideration should be given to the CNS effects and other effects of alcohol. Special consideration may be prudent in individuals with alcoholism or a history of substance abuse. Patients should be cautioned regarding driving or operating machinery following infusion of Taxol as the high alcohol content infused over a short period of time may theoretically cause impairment in some persons.
Children
The safe and effective use of paclitaxel in children has not been established. There have been reports of central nervous system toxicity, rarely associated with death, in a pediatric clinical trial in which Taxol was infused at doses ranging from 350—420 mg/m2 IV over 3 hours. The toxicity is thought to be due to the high concentration of alcohol in the Taxol vehicle and the short infusion time. However, the effect of antihistamine premedication and the high dose of paclitaxel used in this study, over twice the adult recommended dose, cannot be discounted as possible attributing factors.
Extravasation, intramuscular administration, subcutaneous administration
Paclitaxel is considered a vesicant. Extravasation of paclitaxel infusions should be avoided as tissue necrosis has been reported following paclitaxel extravasation. Patients should be closely monitored during IV infusions for signs and symptoms of extravasation such as pain, swelling and poor blood return. In some cases the onset of the extravasation reaction either occurred during a prolonged infusion or was delayed by 7 to 10 days. Patients who have previously experienced a paclitaxel extravasation may have a 'recall' reaction at the previous extravasation site during subsequent paclitaxel infusions. It is recommended that prolonged paclitaxel infusions not be given through peripheral lines due to the potential for severe reactions if extravasated. Intramuscular administration and subcutaneous administration of paclitaxel should be avoided.
Accidental exposure, ocular exposure
Use care to avoid accidental exposure to paclitaxel during preparation, handling and administration. The use of protective gowns, gloves and goggles is recommended. Avoid ocular exposure of paclitaxel solutions. If exposure occurs, the eye should be rinsed immediately and thoroughly; seek medical attention.
Vaccination
Vaccination during chemotherapy with paclitaxel or radiation therapy should be avoided because the antibody response is suboptimal. When chemotherapy is being planned, vaccination should precede the initiation of chemotherapy by >= 2 weeks. The administration of live vaccines to immunocompromised patients should be avoided. Those undergoing chemotherapy should not be exposed to others who have recently received the oral poliovirus vaccine (OPV). Measles-mumps-rubella (MMR) vaccination is not contraindicated for the close contacts, including health care professionals, of immunocompromised patients. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination. When exposed to a vaccine-preventable disease such as measles, severely immunocompromised children should be considered susceptible regardless of their vaccination history.
DRUG INTERACTIONS
Acetaminophen; Ibuprofen: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Adagrasib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with adagrasib is necessary due to the risk of increased plasma concentrations of paclitaxel. 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.
Amlodipine; Celecoxib: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Amoxicillin; Clarithromycin; Omeprazole: (Minor) Paclitaxel is partially metabolized by CYP3A4. The systemic clearance of paclitaxel may be decreased if coadministered with clarithromycin, an inhibitor of CYP3A4.
Apalutamide: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with apalutamide is necessary. Paclitaxel is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer.
Aprepitant, Fosaprepitant: (Moderate) Aprepitant, fosaprepitant is indicated for the prophylaxis of chemotherapy-induced nausea/vomiting and is often used in combination with paclitaxel. However, use caution and monitor for a possible increase in non-emetogenic paclitaxel-related adverse effects for several days after administration of a multi-day aprepitant regimen. Paclitaxel is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer. The AUC of another CYP3A4 substrate, midazolam, was significantly increased when coadministered with oral aprepitant; theoretically, this could also occur with paclitaxel. However, oral aprepitant was commonly administered with paclitaxel in clinical trials without dose adjustments for potential drug interactions; the aprepitant manufacturer does not recommend a paclitaxel dose adjustment. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction.
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. 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.
Atazanavir: (Moderate) Due to atazanavir-induced inhibition of CYP3A4 isoenzymes, atazanavir may inhibit the metabolism and thus, increase the serum concentrations of drugs that are largely metabolized via CYP3A4 including paclitaxel. If atazanavir and paclitaxel must be coadministered, the dosage of paclitaxel may need to be downwardly adjusted and conversely, upward dosage adjustment of paclitaxel may be required when atazanavir is discontinued.
Atazanavir; Cobicistat: (Moderate) Due to atazanavir-induced inhibition of CYP3A4 isoenzymes, atazanavir may inhibit the metabolism and thus, increase the serum concentrations of drugs that are largely metabolized via CYP3A4 including paclitaxel. If atazanavir and paclitaxel must be coadministered, the dosage of paclitaxel may need to be downwardly adjusted and conversely, upward dosage adjustment of paclitaxel may be required when atazanavir is discontinued. (Moderate) Plasma concentrations of paclitaxel may be elevated when administered concurrently with cobicistat. Cobicistat is a strong inhibitor of CYP3A4 and P-glycoprotein (P-gp) inhibitor, while paclitaxel is a CYP3A4 and P-gp substrate. Some experts state that pharmacokinetic interactions between paclitaxel and some CYP3A4 inhibitors do not appear to be clinically significant. However, combining the drugs in clinical practice may require close monitoring to ensure proper therapeutic responses.
Barbiturates: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. Potential interactions may occur in vivo with any agent that induces CYP2C8 or CYP3A4 isoenzymes including barbiturates.
Belzutifan: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with belzutifan is necessary due to the risk of decreased plasma concentrations of paclitaxel. 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 paclitaxel with berotralstat is necessary due to the risk of increased plasma concentrations of paclitaxel. 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.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Medications with significant alcohol content should not be ingested during therapy with metronidazole and should be avoided for 3 days after therapy is discontinued. Some formulations of paclitaxel contain a high level of ethanol. Administration to patients receiving or who have recently received metronidazole may result in disulfiram-like reactions. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Medications with significant alcohol content should not be ingested during therapy with metronidazole and should be avoided for 3 days after therapy is discontinued. Some formulations of paclitaxel contain a high level of ethanol. Administration to patients receiving or who have recently received metronidazole may result in disulfiram-like reactions. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations.
Bortezomib: (Minor) Monitor patients for the development of peripheral neuropathy when receiving bortezomib in combination with other drugs that can cause peripheral neuropathy like paclitaxel; the risk of peripheral neuropathy may be additive.
Bosentan: (Minor) Co-administration of bosentan with other drugs which are metabolized by hepatic enzymes has not been studied. Bosentan is an inducer of cytochrome P450 enzymes, specifically the CYP2C9 and CYP3A4 isoenzymes, and may decrease concentrations of drugs metabolized by these enzymes including paclitaxel.
Brigatinib: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with brigatinib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A4 substrate and brigatinib is a weak CYP3A4 inducer.
Bupivacaine; Meloxicam: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Cabozantinib: (Minor) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with cabozantinib is necessary; a dose adjustment of paclitaxel may be necessary. Paclitaxel is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Carbamazepine: (Moderate) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. Potential interactions may occur in vivo with any agent that induces CYP2C8 or CYP3A4 isoenzymes including carbamazepine. Clinicians should be alert to changes in the clinical effects of paclitaxel. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with paclitaxel.
Carboplatin: (Minor) In vitro studies have shown an increase in cytotoxicity with either the simultaneous or sequential administration of paclitaxel and carboplatin. It appears that paclitaxel followed by carboplatin is more cytotoxic. The pharmacokinetics of either agent is not affected by this sequence of administration.
Celecoxib: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Celecoxib; Tramadol: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Cenobamate: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with cenobamate is necessary due to the risk of decreased paclitaxel concentrations of paclitaxel. 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 with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor and paclitaxel is metabolized by CYP3A4. 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.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
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.
Clarithromycin: (Minor) Paclitaxel is partially metabolized by CYP3A4. The systemic clearance of paclitaxel may be decreased if coadministered with clarithromycin, an inhibitor of CYP3A4.
Clopidogrel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with clopidogrel is necessary due to the risk of increased plasma concentrations of paclitaxel. 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) Plasma concentrations of paclitaxel may be elevated when administered concurrently with cobicistat. Cobicistat is a strong inhibitor of CYP3A4 and P-glycoprotein (P-gp) inhibitor, while paclitaxel is a CYP3A4 and P-gp substrate. Some experts state that pharmacokinetic interactions between paclitaxel and some CYP3A4 inhibitors do not appear to be clinically significant. However, combining the drugs in clinical practice may require close monitoring to ensure proper therapeutic responses.
Conivaptan: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with conivaptan is necessary due to the risk of increased plasma concentrations of paclitaxel. 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 with crizotinib is necessary. Paclitaxel is a CYP3A4 substrate and crizotinib is a moderate CYP3A inhibitor.
Cyclophosphamide: (Moderate) Closely monitor complete blood counts if coadministration of cyclophosphamide with paclitaxel is necessary. Increased hematologic toxicity has been reported when cyclophosphamide was administered after paclitaxel infusion.
Cyclosporine: (Major) In vitro, the metabolism of paclitaxel is inhibited by cyclosporine, but cyclosporine concentrations used exceeded those found in vivo following normal therapeutic doses used in transplantation. Additionally, cyclosporine blocks the multidrug resistance (MDR) P-glycoprotein, which is a mechanism of resistance to naturally occurring (non-synthetic) chemotherapy agents. These agents could enhance paclitaxel's activity and toxicity. Paclitaxel has poor oral availability due to its high affinity for P-glycoprotein present in high levels in the GI tract. In clinical studies, oral paclitaxel has been given in combination with cyclosporine to improve the bioavailability of paclitaxel, due to cyclosporine-induced blockade of P-glycoprotein located in the in GI tract. The bioavailability of oral paclitaxel was 8-fold higher when given in combination with cyclosporine than after oral paclitaxel alone. Therapeutic concentrations were achieved within 7.4 hours, comparable to an equivalent IV dose.
Daclatasvir: (Moderate) Systemic exposure of paclitaxel, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of paclitaxel; monitor patients for potential adverse effects.
Darunavir; Cobicistat: (Moderate) Plasma concentrations of paclitaxel may be elevated when administered concurrently with cobicistat. Cobicistat is a strong inhibitor of CYP3A4 and P-glycoprotein (P-gp) inhibitor, while paclitaxel is a CYP3A4 and P-gp substrate. Some experts state that pharmacokinetic interactions between paclitaxel and some CYP3A4 inhibitors do not appear to be clinically significant. However, combining the drugs in clinical practice may require close monitoring to ensure proper therapeutic responses.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Plasma concentrations of paclitaxel may be elevated when administered concurrently with cobicistat. Cobicistat is a strong inhibitor of CYP3A4 and P-glycoprotein (P-gp) inhibitor, while paclitaxel is a CYP3A4 and P-gp substrate. Some experts state that pharmacokinetic interactions between paclitaxel and some CYP3A4 inhibitors do not appear to be clinically significant. However, combining the drugs in clinical practice may require close monitoring to ensure proper therapeutic responses.
Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Minor) Concurrent administration of paclitaxel (or nanoparticle albumin-bound paclitaxel) with dasabuvir; ombitasvir; paritaprevir; ritonavir may result in increased paclitaxel plasma concentrations and risk for toxicity. Caution and close monitoring are advised if these drugs are administered together. Paclitaxel is metabolized by the hepatic isoenzymes CYP2C8 and CYP3A4; ritonavir is a potent CYP3A4 inhibitor. In addition, paclitaxel is a substrate of the drug transporter P-glycoprotein (P-gp), and ritonavir also inhibits P-gp. Paritaprevir also inhibits P-gp. (Minor) Due to ritonavir's potential inhibitory effects on various hepatic isoenzymes, numerous drug interactions may occur with ritonavir. Close monitoring of serum drug concentrations and/or therapeutic and adverse effects is required when paclitaxel (a CYP2C8 and CYP3A4 substrate) is coadministered with ritonavir (a CYP3A4 inhibitor). In addition, paclitaxel is a substrate of the drug transporter P-glycoprotein (P-gp), and ritonavir also inhibits P-gp.
Deferasirox: (Moderate) Deferasirox inhibits CYP2C8. Paclitaxel is a substrate for CYP2C8. The concomitant administration of deferasirox and the CYP2C8 substrate repaglinide (single dose of 0.5 mg) resulted in an increase in repaglinide Cmax by 62% and an increase in AUC 2.3-fold. Although specific drug interaction studies of deferasirox and paclitaxel are not available, a similar interaction may occur. The dose of paclitaxel may need to be decreased if coadministered with deferasirox.
Delavirdine: (Minor) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as paclitaxel, should be expected with concurrent use of delavirdine.
Diclofenac: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diclofenac; Misoprostol: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diflunisal: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diltiazem: (Minor) Additive bradycardia may occur in patients receiving paclitaxel and other drugs known to cause bradycardia, such as certain calcium-channel blockers, such as diltiazem. These patients should be monitored carefully. Paclitaxel is metabolized by hepatic cytochrome P450 (CYP) isoenzymes 2C8 and 3A4. Paclitaxel metabolism may be inhibited by diltiazem, a moderate CYP3A4 inhibitor. Combining the drugs in clinical practice may require close monitoring to ensure proper therapeutic responses; monitor patients for symptoms and signs of toxicity, such as myelosuppression and peripheral neuropathy.
Diphenhydramine; Ibuprofen: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diphenhydramine; Naproxen: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Disulfiram: (Major) Some formulations of paclitaxel injection contain a high level of ethanol. Administration to patients receiving or who have recently received disulfiram may result in disulfiram-like reactions. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations.
Doxorubicin Liposomal: (Moderate) Use paclitaxel and doxorubicin together with caution. Administer doxorubicin prior to paclitaxel; the AUC values of doxorubicin and its metabolites may increase if paclitaxel is given first. Paclitaxel and doxorubicin are both CYP3A4 substrates.
Doxorubicin: (Moderate) Use paclitaxel and doxorubicin together with caution. Administer doxorubicin prior to paclitaxel; the AUC values of doxorubicin and its metabolites may increase if paclitaxel is given first. Paclitaxel and doxorubicin are both CYP3A4 substrates.
Dronedarone: (Moderate) Dronedarone is metabolized by and is an inhibitor of CYP3A; dronedarone also inhibits P-gp. Paclitaxel is a substrate for CYP3A4 and P-gp. The concomitant administration of dronedarone with CYP3A4 and P-gp substrates may result in increased exposure of the substrate and should, therefore, be undertaken with caution.
Duvelisib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with duvelisib is necessary. Coadministration may increase the exposure of paclitaxel. Paclitaxel is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor.
Efavirenz: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as paclitaxel.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as paclitaxel.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as paclitaxel.
Elbasvir; Grazoprevir: (Moderate) Administering paclitaxel with elbasvir; grazoprevir may result in elevated paclitaxel plasma concentrations. Paclitaxel is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Monitor for paclitaxel-related adverse reactions during coadministration of elexacaftor; tezacaftor; ivacaftor as concurrent use may increase exposure of paclitaxel. Paclitaxel is a substrate for the transporters OATP1B1 and OATP1B3; elexacaftor; tezacaftor; ivacaftor may inhibit uptake of OATP1B1 and OATP1B3.
Eltrombopag: (Moderate) Monitor patients for paclitaxel adverse reactions if coadministered with eltrombopag. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as paclitaxel, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Plasma concentrations of paclitaxel may be elevated when administered concurrently with cobicistat. Cobicistat is a strong inhibitor of CYP3A4 and P-glycoprotein (P-gp) inhibitor, while paclitaxel is a CYP3A4 and P-gp substrate. Some experts state that pharmacokinetic interactions between paclitaxel and some CYP3A4 inhibitors do not appear to be clinically significant. However, combining the drugs in clinical practice may require close monitoring to ensure proper therapeutic responses.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Plasma concentrations of paclitaxel may be elevated when administered concurrently with cobicistat. Cobicistat is a strong inhibitor of CYP3A4 and P-glycoprotein (P-gp) inhibitor, while paclitaxel is a CYP3A4 and P-gp substrate. Some experts state that pharmacokinetic interactions between paclitaxel and some CYP3A4 inhibitors do not appear to be clinically significant. However, combining the drugs in clinical practice may require close monitoring to ensure proper therapeutic responses.
Emapalumab: (Moderate) Monitor for decreased efficacy of paclitaxel and adjust the dose as needed during coadministration with emapalumab. Paclitaxel is a CYP2C8 substrate with a narrow therapeutic range. Emapalumab may normalize CYP450 activity, which may decrease the efficacy of drugs that are CYP450 substrates due to increased metabolism.
Enzalutamide: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with enzalutamide is necessary. Paclitaxel is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer.
Epirubicin: (Moderate) Monitor for an increase in epirubicin-related adverse reactions, including hematologic and gastrointestinal toxicities, if coadministration with paclitaxel is necessary. Coadministration of paclitaxel immediately before or after epirubicin increased the mean AUC of epirubicin by 5% to 109%; the mean AUC of epirubicinol and 7-deoxy-aglycone (inactive metabolites) increased by 120% and 70%, respectively, when paclitaxel was administered immediately after epirubicin. Epirubicin had no effect on the exposure of paclitaxel.
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: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 (CYP) isoenzymes 2C8 and 3A4. Erythromycin is a CYP3A4 inhibitor. In vitro, the metabolism of paclitaxel is inhibited by various agents (e.g., ketoconazole, verapamil, diazepam, quinidine, dexamethasone, tenopiside, etoposide, and vincristine) but concentrations used exceeded those found in vivo following normal therapeutic doses. Closely monitor patients for toxicity when administering paclitaxel with any of these agents.
Etodolac: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Etravirine: (Moderate) Etravirine is a CYP3A4 inducer/substrate and a P-glycoprotein (PGP) inhibitor and paclitaxel is a CYP3A4 and PGP substrate. Caution is warranted if these drugs are coadministered.
Fedratinib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with fedratinib is necessary. Coadministration may increase the exposure of paclitaxel. Paclitaxel is a CYP3A4 substrate and fedratinib is a moderate CYP3A4 inhibitor.
Fenofibrate: (Minor) Paclitaxel is a substrate of CYP2C8, and fenofibrate is a CYP2C8 inhibitor. If coadministration is necessary, use caution and monitor for increased paclitaxel side effects, including myelosuppression and peripheral neuropathy.
Fenofibric Acid: (Minor) Paclitaxel is a substrate of CYP2C8, and fenofibric acid is a weak CYP2C8 inhibitor. If coadministration is necessary, use caution and monitor for increased paclitaxel side effects, including myelosuppression and peripheral neuropathy.
Fenoprofen: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Filgrastim, G-CSF: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert their toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Fluconazole: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. The metabolism of paclitaxel may be inhibited by drugs that inhibit these enzymes, including fluconazole. Closely monitor patients for toxicity when administering paclitaxel with fluconazole.
Fluoxetine: (Minor) Paciltaxel is metabolized by cytochrome P450 3A enzymes. Drugs that inhibit the CYP3A enzymes, such as fluoxetine, can significantly reduce the metabolism of paclitaxel.
Flurbiprofen: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Fluvoxamine: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. Inhibitors of these enzymes, such as fluvoxamine, may increase the serum concentration of paclitaxel. Closely monitor patients for toxicity when administering paclitaxel with fluvoxamine.
Fosamprenavir: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with fosamprenavir is necessary due to the risk of increased plasma concentrations of paclitaxel. 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.
Gadobenate Dimeglumine: (Moderate) Gadobenate dimeglumine is a substrate for the canalicular multi-specific organic anion transporter (MOAT). Use with other MOAT substrates, such as paclitaxel, may result in prolonged systemic exposure of the coadministered drug. Caution is advised if these drugs are used together.
Gemfibrozil: (Major) Paclitaxel is a substrate of CYP2C8 and gemfibrozil is a potent CYP2C8 inhibitor. Paclitaxel concentrations are expected to increase with the co-use of gemfibrozil. Consider alternative therapy to gemfibrozil. If coadministration is necessary, use caution and monitor for increased paclitaxel side effects, including myelosuppression and peripheral neuropathy.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and paclitaxel as coadministration may increase serum concentrations of paclitaxel and increase the risk of adverse effects. Paclitaxel is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and paclitaxel as coadministration may increase serum concentrations of paclitaxel and increase the risk of adverse effects. Paclitaxel is a substrate of P-glycoprotein (P-gp); pibrentasvir is a P-gp inhibitor.
Grapefruit juice: (Major) Advise patients to avoid grapefruit juice while taking paclitaxel due to the risk of increased paclitaxel exposure. Paclitaxel is a CYP3A4 substrate and grapefruit juice is a strong CYP3A4 inhibitor.
Hydantoins: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. Potential interactions may occur in vivo with any agent that induces CYP2C8 or CYP3A4 isoenzymes including hydantoins. This combination could potentially decrease chemotherapy efficacy.
Hydrocodone; Ibuprofen: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Famotidine: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Oxycodone: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with paclitaxel, a CYP3A substrate, as paclitaxel toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Imatinib: (Minor) Imatinib is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering imatinib with other CYP3A4 substrates including paclitaxel.
Indinavir: (Minor) Indinavir inhibits cytochrome P450 3A4. Although specific interactions have not been studied, Indinavir may reduce the metabolism of CYP3A4 substrates, such as paclitaxel, and caution is warranted with coadministration.
Indomethacin: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with paclitaxel may result in increased serum concentrations of paclitaxel. Paclitaxel is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. Closely monitor patients for possibly decreased efficacy when administering paclitaxel with any agent that induces CYP2C8 or CYP3A4 isoenzymes, such as rifampin.
Isoniazid, INH; Rifampin: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. Closely monitor patients for possibly decreased efficacy when administering paclitaxel with any agent that induces CYP2C8 or CYP3A4 isoenzymes, such as rifampin.
Itraconazole: (Minor) Due to itraconazole-induced inhibition of cytochrome P450 3A4, interactions are possible with agents that are substrates of this enzyme including paclitaxel.
Ketoconazole: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with ketoconazole is necessary due to the risk of increased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A4 substrate and ketoconazole 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.
Ketoprofen: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ketorolac: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Lansoprazole; Amoxicillin; Clarithromycin: (Minor) Paclitaxel is partially metabolized by CYP3A4. The systemic clearance of paclitaxel may be decreased if coadministered with clarithromycin, an inhibitor of CYP3A4.
Lansoprazole; Naproxen: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Lapatinib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with lapatinib is necessary. Paclitaxel is a CYP3A4 and P-glycoprotein (P-gp) substrate. Lapatinib is a weak CYP3A4 inhibitor as well as a P-gp inhibitor. The 24-hour systemic exposure (AUC) of paclitaxel was increased by 23% in cancer patients receiving concomitant lapatinib; this increase in paclitaxel exposure may have been underestimated from the in vivo evaluation due to study design limitations.
Ledipasvir; Sofosbuvir: (Minor) Caution and close monitoring of paclitaxel-associated adverse reactions is advised with concomitant administration of ledipasvir. Paclitaxel is a substrate of the drug transporter P-glycoprotein (P-gp); ledipasvir is a P-gp inhibitor. Taking these drugs together may increase paclitaxel plasma concentrations.
Lefamulin: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with oral lefamulin is necessary. Coadministration may increase the exposure of paclitaxel. Paclitaxel is a CYP3A4 substrate and oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin.
Leflunomide: (Moderate) Closely monitor for for paclitaxel-induced side effects when these drugs are used together. In some patients, a dosage reduction of paclitaxel may be required. Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide's in vivo activity. Paclitaxel is a substrate for CYP2C8. In vivo data suggest that teriflunomide is an inhibitor of CYP2C8, as Cmax and AUC increased 1.7- and 4.2-fold, respectively, following concurrent use of another CYP2C8 substrate.
Lenacapavir: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with lenacapavir is necessary due to the risk of increased plasma concentrations of paclitaxel. 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) An increase in the plasma concentration of paclitaxel may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Paclitaxel is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
Levoketoconazole: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with ketoconazole is necessary due to the risk of increased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A4 substrate and ketoconazole 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.
Live Vaccines: (Contraindicated) Do not administer live vaccines to paclitaxel recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving paclitaxel. At least 2 weeks before initiation of paclitaxel therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Paclitaxel recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Lonafarnib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with lonafarnib is necessary due to the risk of increased plasma concentrations of paclitaxel. 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: (Minor) Due to ritonavir's potential inhibitory effects on various hepatic isoenzymes, numerous drug interactions may occur with ritonavir. Close monitoring of serum drug concentrations and/or therapeutic and adverse effects is required when paclitaxel (a CYP2C8 and CYP3A4 substrate) is coadministered with ritonavir (a CYP3A4 inhibitor). In addition, paclitaxel is a substrate of the drug transporter P-glycoprotein (P-gp), and ritonavir also inhibits P-gp.
Lorlatinib: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with lorlatinib is necessary. Paclitaxel is a CYP3A4 substrate and lorlatinib is a moderate CYP3A4 inducer.
Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may alter the therapeutic effects of paclitaxel; caution and close monitoring are advised if these drugs are used together. The paclitaxel dosage may need to be adjusted. Paclitaxel is metabolized by CYP3A4 (and CYP2C8) and is a substrate of the P-glycoprotein (P-gp) efflux transporter. Lumacaftor is a strong CYP3A inducer; in vitro data also suggest lumacaftor; ivacaftor may induce and/or inhibit P-gp. Although induction of paclitaxel through the CYP3A pathway may lead to decreased drug efficacy, the net effect of lumacaftor; ivacaftor on P-gp transport is not clear. Monitor the patient for chemotherapeutic efficacy and adverse effects. In a study designed to determine the maximum tolerated dose of paclitaxel, patients receiving concomitant enzyme-inducing anticonvulsants (e.g., phenytoin, carbamazepine, phenobarbital) tolerated significantly higher doses of paclitaxel as compared to those who were not. Although no prospectively validated dosage adjustment regimen is available, this study suggested a possible need to increase the dose of paclitaxel as much as 50% in patients receiving concurrent enzyme-inducing anticonvulsant therapy. Of note, patients receiving enzyme-inducing anticonvulsants experienced a dose-limiting toxicity of central neurotoxicity while those not receiving anticonvulsants experienced dose-limiting toxicities of myelosuppression, GI toxicity, and fatigue.
Mavacamten: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with mavacamten is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Meclofenamate Sodium: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Mefenamic Acid: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Meloxicam: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Metronidazole: (Major) Medications with significant alcohol content should not be ingested during therapy with metronidazole and should be avoided for 3 days after therapy is discontinued. Some formulations of paclitaxel contain a high level of ethanol. Administration to patients receiving or who have recently received metronidazole may result in disulfiram-like reactions. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations.
Mitapivat: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with mitapivat is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and mitapivat is a weak CYP3A inducer.
Mitotane: (Major) Concomitant use of mitotane with paclitaxel should be undertaken with caution as it could result in decreased plasma concentrations of paclitaxel, leading to reduced efficacy. Mitotane is a strong CYP3A4 inducer and paclitaxel is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of paclitaxel.
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.
Nabumetone: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen; Esomeprazole: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Nefazodone: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. Inhibitors of these enzymes, such as nefazodone, may cause increased serum concentration and side effects of paclitaxel. Closely monitor patients for toxicity when administering paclitaxel with any of these agents.
Nelfinavir: (Minor) Nelfinavir may inhibit the metabolism of other substrates of cytochrome P450 3A4 such as paclitaxel.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Netupitant is a moderate inhibitor of CYP3A4 and should be used with caution in patients receiving concomitant medications that are primarily metabolized through CYP3A4, such as paclitaxel. The plasma concentrations of CYP3A4 substrates can increase when co-administered with netupitant. The inhibitory effect on CYP3A4 can last for multiple days. If coadministration is necessary, use caution and monitor for chemotherapeutic related adverse reactions.
Nevirapine: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with nevirapine is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Nicardipine: (Minor) Paclitaxel is a substrate of CYP2C8 and 3A4; in vitro, nicardipine is a moderate inhibitor of both CYP2C8 and 3A4. If coadministration is necessary, use caution and monitor for increased paclitaxel side effects, including myelosuppression and peripheral neuropathy.
Nirmatrelvir; Ritonavir: (Minor) Due to ritonavir's potential inhibitory effects on various hepatic isoenzymes, numerous drug interactions may occur with ritonavir. Close monitoring of serum drug concentrations and/or therapeutic and adverse effects is required when paclitaxel (a CYP2C8 and CYP3A4 substrate) is coadministered with ritonavir (a CYP3A4 inhibitor). In addition, paclitaxel is a substrate of the drug transporter P-glycoprotein (P-gp), and ritonavir also inhibits P-gp.
Nonsteroidal antiinflammatory drugs: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Odevixibat: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with odevixibat is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and odevixibat is a weak CYP3A inducer.
Olanzapine; Fluoxetine: (Minor) Paciltaxel is metabolized by cytochrome P450 3A enzymes. Drugs that inhibit the CYP3A enzymes, such as fluoxetine, can significantly reduce the metabolism of paclitaxel.
Olutasidenib: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with olutasidenib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and olutasidenib is a weak CYP3A inducer.
Omaveloxolone: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with omaveloxolone is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A and CYP2C8 substrate and omaveloxolone is a weak CYP3A and CYP2C8 inducer.
Ombitasvir; Paritaprevir; Ritonavir: (Minor) Concurrent administration of paclitaxel (or nanoparticle albumin-bound paclitaxel) with dasabuvir; ombitasvir; paritaprevir; ritonavir may result in increased paclitaxel plasma concentrations and risk for toxicity. Caution and close monitoring are advised if these drugs are administered together. Paclitaxel is metabolized by the hepatic isoenzymes CYP2C8 and CYP3A4; ritonavir is a potent CYP3A4 inhibitor. In addition, paclitaxel is a substrate of the drug transporter P-glycoprotein (P-gp), and ritonavir also inhibits P-gp. Paritaprevir also inhibits P-gp. (Minor) Due to ritonavir's potential inhibitory effects on various hepatic isoenzymes, numerous drug interactions may occur with ritonavir. Close monitoring of serum drug concentrations and/or therapeutic and adverse effects is required when paclitaxel (a CYP2C8 and CYP3A4 substrate) is coadministered with ritonavir (a CYP3A4 inhibitor). In addition, paclitaxel is a substrate of the drug transporter P-glycoprotein (P-gp), and ritonavir also inhibits P-gp.
Omeprazole; Amoxicillin; Rifabutin: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. Potential interactions may occur in vivo with any agent that induces CYP2C8 or CYP3A4 isoenzymes including rifabutin.
Oritavancin: (Moderate) Paclitaxel is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of paclitaxel may be reduced if these drugs are administered concurrently.
Oxaprozin: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Palifermin: (Moderate) Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents.
Pazopanib: (Moderate) Coadministration of pazopanib (800 mg by mouth once daily) and paclitaxel (80 mg/m2 IV once weekly) resulted in a mean increase of 26% and 31% in paclitaxel AUC and Cmax, respectively.
Penicillamine: (Major) Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity.
Pexidartinib: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with pexidartinib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
Piroxicam: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Pirtobrutinib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with pirtobrutinib is necessary due to the risk of increased plasma concentrations of paclitaxel. 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) Posaconazole and paclitaxel should be coadministered with caution due to an increased potential for adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of paclitaxel. Further, both paclitaxel and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and paclitaxel, ultimately resulting in an increased risk of adverse events.
Ribociclib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with ribociclib is necessary. Paclitaxel is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
Ribociclib; Letrozole: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with ribociclib is necessary. Paclitaxel is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
Rifabutin: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. Potential interactions may occur in vivo with any agent that induces CYP2C8 or CYP3A4 isoenzymes including rifabutin.
Rifampin: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. Closely monitor patients for possibly decreased efficacy when administering paclitaxel with any agent that induces CYP2C8 or CYP3A4 isoenzymes, such as rifampin.
Rifapentine: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with rifapentine is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Ritonavir: (Minor) Due to ritonavir's potential inhibitory effects on various hepatic isoenzymes, numerous drug interactions may occur with ritonavir. Close monitoring of serum drug concentrations and/or therapeutic and adverse effects is required when paclitaxel (a CYP2C8 and CYP3A4 substrate) is coadministered with ritonavir (a CYP3A4 inhibitor). In addition, paclitaxel is a substrate of the drug transporter P-glycoprotein (P-gp), and ritonavir also inhibits P-gp.
Rolapitant: (Moderate) Use caution if paclitaxel and rolapitant are used concurrently, and monitor for paclitaxel-related adverse effects. Paclitaxel is a P-glycoprotein (P-gp) substrate, where an increase in exposure may significantly increase adverse effects; rolapitant is a P-gp inhibitor. When rolapitant was administered with another P-gp substrate, digoxin, the day 1 Cmax and AUC were increased by 70% and 30%, respectively; the Cmax and AUC on day 8 were not studied.
Rufinamide: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as paclitaxel, may occur during concurrent use with rufinamide.
Saquinavir: (Minor) Although saquinavir does not inhibit cytochrome-based metabolism to the same degree as ritonavir, saquinavir may cause elevated plasma concentrations of drugs which are substrates for CYP3A4 isoenzymes including paclitaxel. Patients should be monitored for toxicities associated with paclitaxel.
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.
Simeprevir: (Moderate) Simeprevir, a mild intestinal CYP3A4 inhibitor, may increase the side effects of paclitaxel, which is a CYP3A4 substrate. Monitor patients for adverse effects of paclitaxel, such as myelosuppression, myalgia/arthralgia, and peripheral neuropathy.
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 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.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Plasma concentrations of paclitaxel, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with voxilaprevir, a P-gp inhibitor. Monitor patients for increased side effects if these drugs are administered concurrently.
Sotorasib: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with sotorasib is necessary due to the risk of decreased plasma concentrations of paclitaxel. 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 paclitaxel with spironolactone is necessary due to the risk of increased plasma concentrations of paclitaxel. Paclitaxel is a CYP2C8 substrate and spironolactone is a 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 paclitaxel with spironolactone is necessary due to the risk of increased plasma concentrations of paclitaxel. Paclitaxel is a CYP2C8 substrate and spironolactone is a CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8.
Stiripentol: (Moderate) Consider a dose reduction of paclitaxel when coadministered with stiripentol. Coadministration may increase plasma concentrations of paclitaxel resulting in an increased risk of adverse reactions. Paclitaxel is a substrate of CYP2C8; stiripentol may inhibit CYP2C8 at clinically relevant concentrations.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Minor) Paclitaxel is a substrate of CYP2C8; in vitro, trimethoprim is a mild inhibitor of CYP2C8. If coadministration is necessary, use caution and monitor for increased paclitaxel side effects, including myelosuppression and peripheral neuropathy. This interaction may also be applicable to combination products containing trimethoprim, including sulfamethoxazole; trimethoprim (also known as SMX-TMP or cotrimoxazole).
Sulindac: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Sumatriptan; Naproxen: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Tbo-Filgrastim: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert their toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Telotristat Ethyl: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with telotristat is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A4 substrate and telotristat is a weak CYP3A4 inducer.
Teriflunomide: (Moderate) Increased monitoring is recommended if teriflunomide is administered concurrently with CYP2C8 substrates, such as paclitaxel. In vivo studies demonstrated that teriflunomide is an inhibitor of CYP2C8. Coadministration may lead to increased exposure to CYP2C8 substrates; however, the clinical impact of this has not yet been determined. Monitor for increased adverse effects.
Thalidomide: (Moderate) Thalidomide and other agents that cause peripheral neuropathy such as paclitaxel should be used cautiously due to the potential for additive effects.
Tolmetin: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Trametinib: (Minor) Paclitaxel is a substrate of CYP2C8; in vitro, trametinib is a mild inhibitor of CYP2C8. If coadministration is necessary, use caution and monitor for increased paclitaxel side effects, including myelosuppression and peripheral neuropathy.
Trandolapril; Verapamil: (Minor) Additive bradycardia may occur in patients receiving paclitaxel and other drugs known to cause bradycardia, such as certain calcium-channel blockers. In vitro, the metabolism of paclitaxel via CYP3A4 was inhibited by verapamil, a moderate CYP3A4 inhibitor. However, the verapamil concentrations used exceeded those found in vivo following normal therapeutic doses. Verapamil also blocks the multidrug resistance (MDR) P-glycoprotein, which is a mechanism of resistance to naturally occurring (non-synthetic) chemotherapy agents. Verapamil could enhance paclitaxel's activity and toxicity through this mechanism as well. Small clinical trials have indicated that the coadministration of r-verapamil, an isomer of verapamil, and paclitaxel results in a significant decrease in paclitaxel clearance and an increase in paclitaxel toxicity. Some experts state that pharmacokinetic interactions between paclitaxel and verapamil do not appear to be clinically significant in vivo. However, combining the drugs in clinical practice may require close monitoring; monitor for paclitaxel induced side effects such as myelosuppression, infection, or peripheral neuropathy.
Trimethoprim: (Minor) Paclitaxel is a substrate of CYP2C8; in vitro, trimethoprim is a mild inhibitor of CYP2C8. If coadministration is necessary, use caution and monitor for increased paclitaxel side effects, including myelosuppression and peripheral neuropathy. This interaction may also be applicable to combination products containing trimethoprim, including sulfamethoxazole; trimethoprim (also known as SMX-TMP or cotrimoxazole).
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 with tucatinib is necessary. Tucatinib is a strong CYP3A4 inhibitor and paclitaxel is metabolized by CYP3A4. 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.
Valdecoxib: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Vemurafenib: (Major) Avoid the concomitant use of vemurafenib and paclitaxel; increased paclitaxel exposure may occur. If co-administration is unavoidable, consider a paclitaxel dose reduction and monitor patients carefully for signs and symptoms of paclitaxel toxicity (e.g., neutropenia, peripheral neuropathy). Vemurafenib is a substrate and weak inducer of CYP3A4 and a substrate and inhibitor of P-glycoprotein (P-gp); paclitaxel is a CYP3A4 and P-gp substrate with a narrow therapeutic index.
Verapamil: (Minor) Additive bradycardia may occur in patients receiving paclitaxel and other drugs known to cause bradycardia, such as certain calcium-channel blockers. In vitro, the metabolism of paclitaxel via CYP3A4 was inhibited by verapamil, a moderate CYP3A4 inhibitor. However, the verapamil concentrations used exceeded those found in vivo following normal therapeutic doses. Verapamil also blocks the multidrug resistance (MDR) P-glycoprotein, which is a mechanism of resistance to naturally occurring (non-synthetic) chemotherapy agents. Verapamil could enhance paclitaxel's activity and toxicity through this mechanism as well. Small clinical trials have indicated that the coadministration of r-verapamil, an isomer of verapamil, and paclitaxel results in a significant decrease in paclitaxel clearance and an increase in paclitaxel toxicity. Some experts state that pharmacokinetic interactions between paclitaxel and verapamil do not appear to be clinically significant in vivo. However, combining the drugs in clinical practice may require close monitoring; monitor for paclitaxel induced side effects such as myelosuppression, infection, or peripheral neuropathy.
Vonoprazan; Amoxicillin; Clarithromycin: (Minor) Paclitaxel is partially metabolized by CYP3A4. The systemic clearance of paclitaxel may be decreased if coadministered with clarithromycin, an inhibitor of CYP3A4.
Voriconazole: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with voriconazole is necessary. Paclitaxel is a CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor.
Voxelotor: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with voxelotor is necessary due to the risk of increased plasma concentrations of paclitaxel. 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.
Zafirlukast: (Moderate) Published data indicate zafirlukast inhibits CYP2C8 rather potently. Until further data are available to confirm the absence of drug interactions, CYP2C8 metabolized drugs, such as paclitaxel, may require closer monitoring when used in conjunction with zafirlukast.
Zonisamide: (Minor) Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and paclitaxel is a substrate of P-gp. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when starting or stopping zonisamide or changing the zonisamide dosage in patients also receiving drugs which are P-gp substrates.