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  • CLASSES

    Small Molecule Antineoplastic Multikinase Inhibitors

    BOXED WARNING

    Hepatic disease, hepatotoxicity

    Hepatotoxicity has been reported with pazopanib use, including elevated hepatic enzymes, hyperbilirubinemia, and fatal hepatic failure. Use pazopanib with caution in patients with mild or moderate hepatic disease; patients older than 65 years of age and those taking simvastatin also have an increased risk of hepatotoxicity. Increased ALT levels (more than 3 to 5 times the upper limit of normal) occurred more often in pazopanib-treated patients who were HLA-B*57:01 allele carriers compared with noncarriers in pharmacogenetic analyses. Transaminase elevations typically occur early in the treatment course, most often in the first 18 weeks of therapy. Mild, indirect hyperbilirubinemia may occur in patients with Gilbert's syndrome or in patients with an underlying genetic susceptibility to Gilbert's syndrome [(TA)7/(TA)7 genotype (UGT1A1*28/*28)]. Monitor liver function tests in all patients at baseline; at weeks 3, 5, 7, and 9; at month 3 and month 4; and then periodically as clinically indicated. Increase to weekly monitoring for patients with elevated ALT until the ALT returns to grade 1 or baseline. Based on the severity of hepatotoxicity, an interruption of therapy, dose reduction, or discontinuation of therapy may be necessary.

    DEA CLASS

    Rx

    DESCRIPTION

    Oral multi-tyrosine kinase inhibitor
    For advanced renal cell carcinoma and soft-tissue sarcoma
    Severe and fatal hepatotoxicity has been reported

    COMMON BRAND NAMES

    Votrient

    HOW SUPPLIED

    Votrient Oral Tab: 200mg

    DOSAGE & INDICATIONS

    For the treatment of advanced renal cell cancer.
    Oral dosage
    Adults

    800 mg PO once daily without food (at least 1 hour before or 2 hours after a meal) until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Treatment with pazopanib significantly improved the median progression-free survival (PFS) compared with placebo in patients with locally advanced and/or metastatic renal cell cancer (RCC) who had received either no prior therapy or one prior cytokine-based systemic therapy in a randomized, double-blind phase 3 trial. In the treatment-naive subgroup, median PFS was 11.1 months versus 2.8 months, respectively; in patients who previously received cytokine-based therapy, median PFS was 7.4 months versus 4.2 months, respectively. The response rate was 30% in the pazopanib arm compared with 3% in the placebo arm; the median duration of response for patients treated with pazopanib was 58.7 weeks. Overall survival was 22.9 months for patients randomized to pazopanib and 20.5 months for the placebo arm, including 54% of patients who crossed over from placebo to pazopanib after progression.

    For the treatment of advanced soft-tissue sarcoma in patients who have received prior chemotherapy.
    NOTE: Efficacy of pazopanib for the treatment of adipocytic soft tissue sarcoma or gastrointestinal stromal tumors has not been demonstrated.
    Oral dosage
    Adults

    800 mg PO once daily without food (at least 1 hour before or 2 hours after a meal) until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a randomized, double-blind, placebo-controlled clinical trial in patients with metastatic soft tissue sarcoma (n = 369), the median progression-free survival was significantly improved with pazopanib compared with placebo (4.6 months vs. 1.6 months). Patients in this study were either ineligible for chemotherapy or had received prior chemotherapy including treatment with an anthracycline (2 or more previous chemotherapy regimens, 56%). Overall survival was not significantly improved with pazopanib compared with placebo at the final analysis (12.5 vs. 10.7 months).

    For the treatment of unresectable, locally advanced, or metastatic gastrointestinal stromal tumors (GIST), after progression on or intolerance to both imatinib and sunitinib†.
    Oral dosage
    Adults

    800 mg by mouth once daily until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Median investigator-assessed PFS was significantly improved with pazopanib plus BSC compared with BSC alone (3.4 months vs. 2.3 months) in patients with unresectable, locally advanced, or metastatic GIST after failure of both imatinib and sunitinib in a multicenter, randomized, open-label phase 2 clinical trial. Best overall response per central review was stable disease (84% vs. 71%, respectively), with only one partial response in the BSC group. Median overall survival was 17.8 months in patients treated with pazopanib compared with 12.9 months in those who received BSC; most patients in the BSC arm (88%) crossed over to receive pazopanib after progression.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    800 mg PO/day.

    Elderly

    800 mg PO/day.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Baseline Hepatic Impairment:
    Mild hepatic impairment (normal total bilirubin and ALT level greater than upper limit of normal (ULN) OR total bilirubin 1.1 to 1.5 times ULN with any ALT): Dosage adjustment not necessary.
    Moderate hepatic impairment (total bilirubin 1.6 to 3 times ULN with any ALT): Consider an alternative agent; otherwise, reduce the dose of pazopanib to 200 mg PO once daily.
    Severe hepatic impairment (total bilirubin greater than 3 times ULN with any ALT): Use not recommended.
     
    Treatment-Related Hepatotoxicity:
    Isolated ALT elevations of 3 to 8 times ULN: Continue pazopanib therapy. Monitor liver function weekly until ALT returns to grade 1 or baseline.
    Isolated ALT elevations of more than 8 times ULN: Hold pazopanib therapy. If the potential benefit of pazopanib treatment outweighs the risk of hepatotoxicity, treatment may be resumed at a reduced dose of no more than 400 mg PO once daily when the ALT level improves to grade 1 or baseline. Monitor liver function tests weekly for 8 weeks. Permanently discontinue pazopanib treatment if ALT elevations of greater than 3 times ULN recur despite dose reductions.
    ALT greater than 3 times ULN with concurrent mild, indirect (unconjugated) hyperbilirubinemia (Gilbert's syndrome): Manage per recommendations for isolated ALT elevations.
    ALT greater than 3 times ULN with concurrent bilirubin greater than 2 times ULN: Permanently discontinue pazopanib therapy and monitor liver function tests until resolution.

    Renal Impairment

    No dosage adjustments are necessary.

    ADMINISTRATION

    Hazardous Drugs Classification
    NIOSH 2016 List: Group 1
    NIOSH (Draft) 2020 List: Table 2
    Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
    Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure.
    Emetic Risk
    Minimal/Low
    Administer prn antiemetics as necessary.

    Oral Administration
    Oral Solid Formulations

    •Administer on an empty stomach (1 hour before or 2 hours after a meal). Separate doses by approximately 24 hours.
    •Do not crush tablets due to the potential for an increased rate of absorption, which may affect systemic exposure. Only intact, whole tablets should be administered.
    •If a dose is missed, it should not be taken if it is less than 12 hours until the next dose.

    STORAGE

    Votrient:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Hepatic disease, hepatotoxicity

    Hepatotoxicity has been reported with pazopanib use, including elevated hepatic enzymes, hyperbilirubinemia, and fatal hepatic failure. Use pazopanib with caution in patients with mild or moderate hepatic disease; patients older than 65 years of age and those taking simvastatin also have an increased risk of hepatotoxicity. Increased ALT levels (more than 3 to 5 times the upper limit of normal) occurred more often in pazopanib-treated patients who were HLA-B*57:01 allele carriers compared with noncarriers in pharmacogenetic analyses. Transaminase elevations typically occur early in the treatment course, most often in the first 18 weeks of therapy. Mild, indirect hyperbilirubinemia may occur in patients with Gilbert's syndrome or in patients with an underlying genetic susceptibility to Gilbert's syndrome [(TA)7/(TA)7 genotype (UGT1A1*28/*28)]. Monitor liver function tests in all patients at baseline; at weeks 3, 5, 7, and 9; at month 3 and month 4; and then periodically as clinically indicated. Increase to weekly monitoring for patients with elevated ALT until the ALT returns to grade 1 or baseline. Based on the severity of hepatotoxicity, an interruption of therapy, dose reduction, or discontinuation of therapy may be necessary.

    Angina, myocardial infarction, stroke

    Pazopanib should be used with caution in patients at increased risk for or with a history of angina, myocardial infarction, stroke, or transient ischemic attacks. Arterial thrombotic events such as these have occurred in patients treated with pazopanib in clinical trials, including fatalities. Pazopanib has not been studied in patients who have had an arterial thrombotic event in the previous 6 months. Permanently discontinue pazopanib if an arterial thrombotic event occurs. Myocardial infarction and stroke may increase the risk of prolonging the QT interval when using pazopanib.

    Heart failure

    Use pazopanib with caution in patients with a history of heart failure; decreased left ventricular ejection fraction (LVEF) and congestive heart failure (CHF) have occurred in patients treated with pazopanib. Monitor patients for clinical signs or symptoms of congestive heart failure. Conduct baseline and periodic evaluations of LVEF in patients at risk for cardiac dysfunction, including those with previous anthracycline exposure. An interruption of therapy or discontinuation of therapy may be necessary depending on the severity of cardiac dysfunction.

    Hypothyroidism

    Use pazopanib with caution in patients with hypothyroidism, as it has been reported in patients treated with pazopanib in clinical trials. Monitor thyroid function tests at baseline, during treatment, and as clinically indicated; manage hypothyroidism as appropriate. Hypothyroidism may also increase the risk of prolonging the QT interval when using pazopanib.

    Apheresis, AV block, bradycardia, cardiomyopathy, celiac disease, females, fever, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, long QT syndrome, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, systemic lupus erythematosus (SLE)

    Prolongation of the QT interval has occurred in patients treated with pazopanib; torsade de pointes (TdP) has also been rarely reported. Monitor ECG and electrolytes in patients who are at significant risk of developing QT prolongation, including patients with a history of QT prolongation, in patients taking antiarrhythmics or other medications that may prolong the QT interval, and in those with relevant pre-existing heart disease; correct hypokalemia, hypomagnesemia, and hypocalcemia prior to initiating pazopanib therapy and during treatment. Use pazopanib with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to cause an electrolyte imbalance. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.

    Bleeding, GI bleeding, intracranial bleeding

    Use pazopanib with caution in patients with a history of hemoptysis, intracranial bleeding, or clinically significant GI bleeding in the previous 6 months; pazopanib has not been studied in these populations. Bleeding events, some fatal, have occurred during clinical trials of pazopanib. If a hemorrhagic even occurs, hold pazopanib therapy; a dose reduction or discontinuation of therapy may be necessary.

    Hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura (TTP)

    Thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome, has been reported in patients who received single-agent pazopanib, or pazopanib in combination with bevacizumab or topotecan (off-label use), in clinical trials. Most cases developed within 90 days of starting pazopanib and therapy discontinuation resulted in TMA improvement. Monitor patients for signs and symptoms of TMA; permanently discontinue pazopanib in patients who develop TMA.

    Impaired wound healing, surgery

    Impaired wound healing can occur in patients treated with vascular endothelial growth factor (VEGF) inhibitors such as pazopanib. Discontinue pazopanib at least 1 week prior to elective surgery; do not administer pazopanib for at least 2 weeks following major surgery and until adequate wound healing. The safety of resuming pazopanib after resolution of wound healing complications has not been established.

    Proteinuria

    Pazopanib has occurred in patients treated with pazopanib in clinical trials. Perform a urinalysis at baseline, periodically during treatment, and as clinically indicated for measurement of 24-hour urine protein. Hold pazopanib therapy and then resume at a reduced dose or permanently discontinue based on the severity of proteinuria. Permanently discontinue pazopanib treatment in patients with nephrotic syndrome.

    Pneumonitis

    Pneumonitis and interstitial lung disease (ILD) have been reported with pazopanib use; some cases were fatal. Monitor patients for signs and symptoms of ILD/pneumonitis; discontinue pazopanib in patients who develop pneumonitis or ILD.

    Asian patients, neutropenia, serious rash, thrombocytopenia

    Grade 3 or 4 neutropenia and thrombocytopenia and serious rash (i.e., palmar-plantar erythrodysesthesia/hand and foot syndrome) occurred more often in East Asian patients who received pazopanib compared with non-East Asian patients in pooled results from clinical trials.

    Dehydration, renal impairment, tumor lysis syndrome (TLS)

    Tumor lysis syndrome (TLS) has been reported with pazopanib therapy; fatal cases have occurred. Monitor patients who are at increased risk for developing TLS including patients with rapidly growing tumors, a high tumor burden, renal impairment, or dehydration. Consider TLS prophylaxis in these patients and treat as indicated.

    Hypercholesterolemia

    Use pazopanib with caution in patients with hypercholesterolemia receiving statin therapy. Concomitant use of pazopanib and simvastatin increases the risk of ALT elevations; there are insufficient data available to assess the risk of concomitant administration of alternative statins and pazopanib.

    Hypertension

    Use pazopanib with caution in patients with pre-existing hypertension. Do not initiate therapy in patients with uncontrolled hypertension; optimize blood pressure prior to beginning therapy. Monitor blood pressure as clinically indicated and initiate/adjust antihypertensive therapy as appropriate. Depending on the severity of hypertension, an interruption of therapy, dose reduction, or discontinuation of therapy may be necessary. Hypertension (systolic blood pressure 150 mmHg or more, or diastolic blood pressure 100 mmHg or more) and hypertensive crisis have been observed in patients treated with pazopanib.

    Thromboembolic disease, thrombosis

    Use pazopanib with caution in patients with thromboembolic disease. Venous thromboembolic events (VTE), including venous thrombosis and fatal pulmonary embolus (PE) occurred in patients treated with pazopanib. Monitor patients for signs and symptoms of VTE and PE. Hold pazopanib therapy if a thromboembolic event occurs; a dose reduction or discontinuation of therapy may be necessary based on the severity of the event.

    Fistula, GI perforation

    GI perforation or fistula occurred in patients treated with pazopanib in clinical trials. Monitor for signs and symptoms of a GI perforation or fistula. If a grade 2 or 3 GI fistula occurs, hold pazopanib treatment; resume based on medical judgment. Permenantly discontinue pazopanib therapy in case of GI perforation or grade 4 GI fistula.

    Encephalopathy

    Posterior Reversible Encephalopathy Syndrome (PRES), also known as Reversible Posterior Leukoencephalopathy Syndrome (RPLS), has been reported with pazopanib use. Symptoms include headache, seizures, lethargy, confusion, blindness, and other visual and neurologic disturbances. Confirm a diagnosis of PRES by magnetic resonance imaging (MRI); permanently discontinue pazopanib therapy in patients who develop PRES.

    Children, infants, neonates

    The safety and efficacy of pazopanib has not been established in adolescents, children, infants, and neonates; pazopanib is not indicated for use in pediatric patients. Organ growth and maturation of the lungs, liver, heart, and kidney were severely affected during early post-natal development in animal studies at doses lower than those used in adults; death was also reported. Other abnormalities noted in the post-natal development period in juvenile rats included tooth degeneration and decreased bone growth. Patients under 2 years of age may be at increased risk for these serious adverse events.

    Geriatric

    Use pazopanib with caution in geriatric patients (65 years of age or older). These patients have a greater risk of developing hepatotoxicity and QT prolongation when using pazopanib. Also, across all soft-tissue sarcoma trials, patients 65 years of age or older had a higher incidence of grade 3 or 4 fatigue, hypertension, decreased appetite, ALT elevations, and AST elevations. No overall differences in safety were observed in geriatric patients across the renal cell cancer trials.

    Pregnancy

    Pregnancy should be avoided by females of reproductive potential during pazopanib treatment and for at least 2 weeks after the last dose. Although there are no adequately controlled studies in pregnant women, pazopanib 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 pazopanib should be apprised of the potential hazard to the fetus. Teratogenicity and abortion were observed in rabbits and rats who were administered pazopanib (at doses that resulted in systemic exposures lower than those observed at the maximum human dose of 800 mg/day) during organogenesis. Cardiovascular malformations (e.g., retroesophageal subclavian artery, missing innominate artery, changes in the aortic arch) and incomplete or absent ossification were reported in rats; increased post-implantation loss and abortion occurred in rabbits.

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

    Counsel patients about the reproductive risk and contraception requirements during pazopanib treatment. Pazopanib 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 2 weeks after treatment with pazopanib. Due to the risk of male-mediated teratogenicity, male patients with a female partner of reproductive potential should use effective contraception (i.e., condoms) during pazopanib therapy and for at least 2 weeks after the last dose. Females of reproductive potential should undergo pregnancy testing prior to initiation of pazopanib. Women who become pregnant while receiving pazopanib should be apprised of the potential hazard to the fetus. Although there are no data regarding the effect of pazopanib on human fertility, pazopanib may cause infertility in males and females of reproductive potential while receiving treatment based on animal studies.

    Breast-feeding

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

    ADVERSE REACTIONS

    Severe

    bradycardia / Rapid / 2.0-19.0
    fatigue / Early / 2.0-14.0
    elevated hepatic enzymes / Delayed / 1.0-12.0
    neutropenia / Delayed / 0-12.0
    anorexia / Delayed / 2.0-11.0
    lymphopenia / Delayed / 3.0-10.0
    hypertensive crisis / Early / 4.0-10.0
    proteinuria / Delayed / 1.0-9.0
    heart failure / Delayed / 0.5-8.0
    thrombocytopenia / Delayed / 0-6.0
    dyspnea / Early / 0-6.0
    hyponatremia / Delayed / 4.0-5.0
    diarrhea / Early / 3.0-5.0
    hyperbilirubinemia / Delayed / 1.0-4.0
    hypophosphatemia / Delayed / 0-4.0
    weight loss / Delayed / 0-4.0
    pneumothorax / Early / 0.7-3.3
    bleeding / Early / 1.0-3.0
    nausea / Early / 0-3.0
    vomiting / Early / 2.0-3.0
    asthenia / Delayed / 0-3.0
    myocardial infarction / Delayed / 2.0-2.0
    hypomagnesemia / Delayed / 0-2.0
    palmar-plantar erythrodysesthesia (hand and foot syndrome) / Delayed / 0-2.0
    myalgia / Early / 0-2.0
    musculoskeletal pain / Early / 0-2.0
    abdominal pain / Early / 0-2.0
    chest pain (unspecified) / Early / 0-2.0
    stomatitis / Delayed / 0-2.0
    peripheral edema / Delayed / 0-2.0
    torsade de pointes / Rapid / 0-1.0
    hyperkalemia / Delayed / 0-1.0
    leukopenia / Delayed / 0-1.0
    exfoliative dermatitis / Delayed / 0-1.0
    headache / Early / 0-1.0
    dizziness / Early / 0-1.0
    cough / Delayed / 0-1.0
    hypoalbuminemia / Delayed / 0-1.0
    gastrointestinal fistula / Delayed / 1.0-1.0
    hair discoloration / Delayed / 0-1.0
    GI perforation / Delayed / 0.9-0.9
    stroke / Early / 0.3-0.4
    pancreatitis / Delayed / 1.0
    hepatic failure / Delayed / Incidence not known
    hepatotoxicity / Delayed / Incidence not known
    GI bleeding / Delayed / Incidence not known
    intracranial bleeding / Delayed / Incidence not known
    nephrotic syndrome / Delayed / Incidence not known
    pulmonary embolism / Delayed / Incidence not known
    thrombosis / Delayed / Incidence not known
    infection / Delayed / Incidence not known
    retinal detachment / Delayed / Incidence not known
    thrombotic microangiopathy / Delayed / Incidence not known
    hemolytic-uremic syndrome / Delayed / Incidence not known
    thrombotic thrombocytopenic purpura (TTP) / Delayed / Incidence not known
    leukoencephalopathy / Delayed / Incidence not known
    tumor lysis syndrome (TLS) / Delayed / Incidence not known
    aortic dissection / Delayed / Incidence not known

    Moderate

    hypertension / Early / 35.0-36.0
    hypothyroidism / Delayed / 4.0-8.0
    dysphonia / Delayed / 4.0-8.0
    blurred vision / Early / 0-5.0
    hematuria / Delayed / 0-4.0
    QT prolongation / Rapid / 0.4-2.0
    hemoptysis / Delayed / 0-2.0
    edema / Delayed / 0-1.0
    pneumonitis / Delayed / 0.1-0.1
    interstitial lung disease / Delayed / Incidence not known
    encephalopathy / Delayed / Incidence not known
    polycythemia / Delayed / Incidence not known

    Mild

    dysgeusia / Early / 8.0-28.0
    alopecia / Delayed / 8.0-12.0
    skin hypopigmentation / Delayed / 3.0-11.0
    insomnia / Early / 0-9.0
    epistaxis / Delayed / 2.0-8.0
    dyspepsia / Early / 5.0-7.0
    xerosis / Delayed / 0-6.0
    chills / Rapid / 0-5.0
    arthralgia / Delayed / Incidence not known
    muscle cramps / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abrocitinib: (Major) Avoid coadministration of pazopanib and abrocitinib due to the potential for increased pazopanib exposure. Pazopanib is a P-gp substrate; abrocitinib is a P-gp inhibitor. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit P-gp.
    Acalabrutinib: (Moderate) Coadministration of acalabrutinib and pazopanib may increase pazopanib exposure and increase the risk of pazopanib toxicity. Acalabrutinib is an inhibitor of the breast cancer resistance protein (BCRP) transporter in vitro; it may inhibit intestinal BCRP. Pazopanib is a BCRP substrate.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with pazopanib may alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage adjustment of dihydrocodeine until stable drug effects are achieved. Discontinuation of pazopanib could alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If pazopanib is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Pazopanib is a weak inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase dihydrocodeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
    Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Acetaminophen; Dextromethorphan: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Acetaminophen; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like pazopanib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If pazopanib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Acetaminophen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. If pazopanib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a weak inhibitor like pazopanib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If pazopanib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
    Alfentanil: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and alfentanil, a CYP3A4 substrate, may cause an increase in systemic concentrations of alfentanil. Use caution when administering these drugs concomitantly.
    Alfuzosin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), alfuzosin and pazopanib should be avoided. Based on electrophysiology studies performed by the manufacturer, alfuzosin may prolong the QT interval in a dose-dependent manner. Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation.
    Aliskiren: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and aliskiren, a CYP3A4 substrate, may cause an increase in systemic concentrations of aliskiren. Use caution when administering these drugs concomitantly.
    Aliskiren; Amlodipine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and aliskiren, a CYP3A4 substrate, may cause an increase in systemic concentrations of aliskiren. Use caution when administering these drugs concomitantly. (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and amlodipine, a CYP3A4 substrate, may cause an increase in systemic concentrations of amlodipine. Use caution when administering these drugs concomitantly.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and aliskiren, a CYP3A4 substrate, may cause an increase in systemic concentrations of aliskiren. Use caution when administering these drugs concomitantly. (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and amlodipine, a CYP3A4 substrate, may cause an increase in systemic concentrations of amlodipine. Use caution when administering these drugs concomitantly.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and aliskiren, a CYP3A4 substrate, may cause an increase in systemic concentrations of aliskiren. Use caution when administering these drugs concomitantly.
    Aliskiren; Valsartan: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and aliskiren, a CYP3A4 substrate, may cause an increase in systemic concentrations of aliskiren. Use caution when administering these drugs concomitantly.
    Almotriptan: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and almotriptan, a CYP3A4 substrate, may cause an increase in systemic concentrations of almotriptan. Use caution when administering these drugs concomitantly.
    Alprazolam: (Major) Avoid coadministration of alprazolam and pazopanib due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. If coadministration is necessary, consider reducing the dose of alprazolam as clinically appropriate and monitor for an increase in alprazolam-related adverse reactions. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with pazopanib, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A4 substrate and pazopanib is a weak CYP3A4 inhibitor. Coadministration with another weak CYP3A4 inhibitor increased alprazolam maximum concentration by 82%, decreased clearance by 42%, and increased half-life by 16%.
    Amiodarone: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and amiodarone have been reported to prolong the QT interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. If pazopanib and amiodarone must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a substrate for CYP3A4 and P-glycoprotein (P-gp) and a weak inhibitor of CYP3A4. Amiodarone is a CYP3A4 and P-gp inhibitor and a CYP3A4 substrate. Concurrent administration may result in increased concentrations of pazopanib and/or amiodarone. Use caution if concurrent administration is necessary.
    Amisulpride: (Major) Coadministration of amisulpride and pazopanib is not recommended due to the risk of additive QT prolongation and torsade de pointes (TdP). Amisulpride causes dose- and concentration- dependent QT prolongation. Pazopanib is associated with QT interval prolongation.
    Amitriptyline: (Minor) Coadministration of pazopanib and other drugs that prolong the QT interval, such as tricyclic antidepressants is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Amitriptyline, clomipramine and imipramine are CYP3A4 substrates. Coadministration of pazopanib may cause an increase in systemic concentrations of the tricyclic antidepressant. Use caution when administering these drugs concomitantly.
    Amlodipine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and amlodipine, a CYP3A4 substrate, may cause an increase in systemic concentrations of amlodipine. Use caution when administering these drugs concomitantly.
    Amlodipine; Atorvastatin: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and amlodipine, a CYP3A4 substrate, may cause an increase in systemic concentrations of amlodipine. Use caution when administering these drugs concomitantly. (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and atorvastatin, a CYP3A4 substrate, may cause an increase in systemic concentrations of atorvastatin. Use caution when administering these drugs concomitantly.
    Amlodipine; Benazepril: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and amlodipine, a CYP3A4 substrate, may cause an increase in systemic concentrations of amlodipine. Use caution when administering these drugs concomitantly.
    Amlodipine; Celecoxib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and amlodipine, a CYP3A4 substrate, may cause an increase in systemic concentrations of amlodipine. Use caution when administering these drugs concomitantly.
    Amlodipine; Olmesartan: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and amlodipine, a CYP3A4 substrate, may cause an increase in systemic concentrations of amlodipine. Use caution when administering these drugs concomitantly.
    Amlodipine; Valsartan: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and amlodipine, a CYP3A4 substrate, may cause an increase in systemic concentrations of amlodipine. Use caution when administering these drugs concomitantly.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and amlodipine, a CYP3A4 substrate, may cause an increase in systemic concentrations of amlodipine. Use caution when administering these drugs concomitantly.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and clarithromycin have been reported to prolong the QT interval. If pazopanib and clarithromycin must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a substrate for CYP3A4 and P-glycoprotein (P-gp) and weak inhibitor of CYP3A4. Clarithromycin is a strong inhibitor of CYP3A4, an inhibitor of P-gp, and substrate of CYP3A4. Concurrent administration of clarithromycin and pazopanib may result in increased pazopanib and/or clarithromycin concentrations; avoid use of these agents together if possible. If co-administration of pazopanib and clarithromycin is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. (Major) Pazopanib displays pH-dependent solubility with decreased solubility at a higher pH. The concomitant use of pazopanib and proton pump inhibitors (PPIs) that elevate the gastric pH may reduce the bioavailability of pazopanib. In a study of patients with solid tumors, the AUC and Cmax of pazopanib were decreased by approximately 40% when coadministered with esomeprazole. If a drug is needed to raise the gastric pH, consider use of a short-acting antacid; separate antacid and pazopanib dosing by several hours.
    Amprenavir: (Major) Pazopanib is a weak inhibitor of and a substrate for CYP3A4. Amprenavir is an inhibitor of and a substrate for CYP3A4. Concurrent administration of amprenavir and pazopanib may result in increased pazopanib concentrations and/or increased amprenavir concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and amprenavir is required.
    Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include pazopanib.
    Antacids: (Moderate) Separate administration of pazopanib and antacids by several hours if coadministration is necessary in order to avoid a reduction in pazopanib exposure, which may decrease efficacy.
    Apalutamide: (Major) Avoid coadministration of pazopanib with apalutamide due to the potential for decreased plasma concentrations of pazopanib. Pazopanib is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer.
    Apomorphine: (Major) Concurrent use of pazopanib and apomorphine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be continued, closely monitor the patient for QT interval prolongation. Pazopanib has been reported to prolong the QT interval. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
    Aprepitant, Fosaprepitant: (Major) Use caution if pazopanib and aprepitant, fosaprepitant are used concurrently and monitor for an increase in pazopanib-related adverse effects for several days after administration of a multi-day aprepitant regimen. Pazopanib 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 and may increase plasma concentrations of pazopanib. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. 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. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important. Pazopanib is also a weak CYP3A4 inhibitor and aprepitant is a CYP3A4 substrate. Coadministration of daily oral aprepitant (230 mg, or 1.8 times the recommended single dose) with a moderate CYP3A4 inhibitor, diltiazem, increased the aprepitant AUC 2-fold with a concomitant 1.7-fold increase in the diltiazem AUC; clinically meaningful changes in ECG, heart rate, or blood pressure beyond those induced by diltiazem alone did not occur. Information is not available regarding the use of aprepitant with weak CYP3A4 inhibitors.
    Aripiprazole: (Major) Because both pazopanib and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and aripiprazole, a CYP3A4 substrate, may cause an increase in systemic concentrations of aripiprazole. Close monitoring is recommended for aripiprazole-related adverse effects. Because aripiprazole is also metabolized by CYP2D6, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adults receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inhibitor.
    Arsenic Trioxide: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include pazopanib.
    Artemether; Lumefantrine: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and artemether; lumefantrine have been reported to prolong the QT interval. If pazopanib and artemether; lumefantrine must be continued, closely monitor the patient for QT interval prolongation. Consider ECG monitoring if pazopanib must be used with or after artemether; lumefantrine treatment. In addition, pazopanib is a weak inhibitor of CYP3A4 and a substrate for CYP2D6, while artemether; lumefantrine is a CYP3A4 substrate and inhibitor of CYP2D6. Coadministration may cause an increase in systemic concentrations of both drugs. Use caution when concurrent administration of artemether; lumefantrine and pazopanib is necessary.
    Asenapine: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and asenapine have been reported to prolong the QT interval. According to the manufacturer of asenapine, the drug should be avoided in combination with other agents also known to have this effect. If pazopanib and asenapine must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and asenapine, a CYP3A4 substrate, may cause an increase in systemic concentrations of asenapine. Use caution when concurrent administration of asenapine and pazopanib is necessary.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with pazopanib may alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage adjustment of dihydrocodeine until stable drug effects are achieved. Discontinuation of pazopanib could alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If pazopanib is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Pazopanib is a weak inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase dihydrocodeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Separate administration of pazopanib and antacids by several hours if coadministration is necessary in order to avoid a reduction in pazopanib exposure, which may decrease efficacy.
    Aspirin, ASA; Omeprazole: (Major) Pazopanib displays pH-dependent solubility with decreased solubility at a higher pH. The concomitant use of pazopanib and proton pump inhibitors (PPIs) that elevate the gastric pH may reduce the bioavailability of pazopanib. In a study of patients with solid tumors, the AUC and Cmax of pazopanib were decreased by approximately 40% when coadministered with esomeprazole. If a drug is needed to raise the gastric pH, consider use of a short-acting antacid; separate antacid and pazopanib dosing by several hours.
    Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. If pazopanib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a weak inhibitor like pazopanib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If pazopanib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
    Atazanavir: (Major) Avoid administering pazopanib with strong CYP3A4 inhibitors, such as atazanavir. If co-administration with a strong CYP3A4 inhibitor is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. The concomitant use of pazopanib, a weak CYP3A4 inhibitor and a CYP3A4 and CYP2C8 substrate, and atazanavir, a CYP3A4 and CYP2C8 inhibitor and a substrate for CYP3A4, may result in altered pazopanib and/or atazanavir concentrations.
    Atazanavir; Cobicistat: (Major) Avoid administering pazopanib with strong CYP3A4 inhibitors, such as atazanavir. If co-administration with a strong CYP3A4 inhibitor is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. The concomitant use of pazopanib, a weak CYP3A4 inhibitor and a CYP3A4 and CYP2C8 substrate, and atazanavir, a CYP3A4 and CYP2C8 inhibitor and a substrate for CYP3A4, may result in altered pazopanib and/or atazanavir concentrations. (Major) Avoid coadministration of pazopanib and cobicistat due to the potential for increased exposure of both pazopanib and cobicistat. If concurrent use is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. Pazopanib is an inhibitor and substrate of CYP3A4; cobicistat is a strong CYP3A4 inhibitor and a CYP3A4 substrate. Concurrent use of pazopanib another strong CYP3A4 inhibitor increased the Cmax and AUC of pazopanib by 1.5-fold and 1.7-fold, respectively. In addition, pazopanib is a substrate/inhibitor of P-glycoprotein (P-gp), an inhibitor of CYP2D6, and a substrate of breast cancer resistance protein (BCRP). Cobicistat is an inhibitor of P-gp, BCRP, and a substrate/inhibitor of CYP2D6.
    Atomoxetine: (Major) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Atomoxetine is considered a drug with a possible risk of torsade de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with atomoxetine include pazopanib.
    Atorvastatin: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and atorvastatin, a CYP3A4 substrate, may cause an increase in systemic concentrations of atorvastatin. Use caution when administering these drugs concomitantly.
    Atorvastatin; Ezetimibe: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and atorvastatin, a CYP3A4 substrate, may cause an increase in systemic concentrations of atorvastatin. Use caution when administering these drugs concomitantly.
    Azithromycin: (Major) Avoid coadministration of azithromycin with pazopanib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Pazopanib has been reported to prolong the QT interval.
    Bedaquiline: (Major) Caution is advised when administering bedaquiline concurrently with pazopanib. Pazopanib may inhibit the CYP3A4 metabolism of bedaquiline resulting in increased systemic exposure (AUC) and potentially more adverse reactions. Furthermore, since both drugs are associated with QT prolongation, coadministration may result in additive prolongation of the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Avoid administering pazopanib in patients who require chronic treatment with a strong CYP3A4 inducer, such as phenobarbital. The concomitant use of pazopanib, a CYP3A4 substrate, and phenobarbital, a strong CYP3A4 inducer, may result in decreased pazopanib concentrations. (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and ergotamine, a CYP3A4 substrate, may cause an increase in systemic concentrations of ergotamine. Use caution when administering these drugs concomitantly.
    Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with pazopanib may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Consider a dose reduction of benzhydrocodone until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. Discontinuation of pazopanib in a patient taking benzhydrocodone may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If pazopanib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a substrate for CYP3A4 and CYP2D6. Pazopanib is a weak inhibitor of CYP3A4 and CYP2D6.
    Bepridil: (Contraindicated) Pazopanib is a weak inhibitor of CYP3A4 and a substrate for P-glycoprotein (Pgp). Coadministration of pazopanib and bepridil, a CYP3A4 substrate, may cause an increase in systemic concentrations of bepridil. In addition, bepridil is an inhibitor of Pgp and may cause an increase in systemic concentrations of pazopanib.
    Berotralstat: (Major) Avoid coadministration of pazopanib and berotralstat due to the potential for increased pazopanib exposure. Pazopanib is a P-gp substrate; berotralstat is a P-gp inhibitor. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit P-gp.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and pazopanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and pazopanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Boceprevir: (Major) Avoid administering pazopanib with strong CYP3A4 inhibitors, such as boceprevir. If co-administration with a strong CYP3A4 inhibitor is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. The concomitant use of pazopanib, a weak CYP3A4 inhibitor and a CYP3A4 and P-glycoprotein (P-gp) substrate, and boceprevir, a strong CYP3A4 inhibitor and a P-gp inhibitor and substrate, may result in altered pazopanib and/or boceprevir concentrations.
    Bortezomib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and bortezomib, a CYP3A4 substrate, may cause an increase in systemic concentrations of bortezomib. Use caution when administering these drugs concomitantly.
    Bosentan: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and bosentan, a CYP3A4 substrate, may cause an increase in systemic concentrations of bosentan. Use caution when administering these drugs concomitantly.
    Brigatinib: (Moderate) Monitor for an increase in pazopanib-related adverse reactions if coadministration with brigatinib is necessary. Pazopanib is a substrate of P-glycoprotein (P-gp) and BCRP. Brigatinib inhibits both P-gp and BCRP in vitro and may have the potential to increase concentrations of substrates of these transporters.
    Bromocriptine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and bromocriptine, a CYP3A4 substrate, may cause an increase in systemic concentrations of bromocriptine. Use caution when administering these drugs concomitantly.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like pazopanib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If pazopanib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like pazopanib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If pazopanib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Budesonide: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and budesonide, a CYP3A4 substrate, may cause an increase in systemic concentrations of budesonide. Use caution when administering these drugs concomitantly.
    Budesonide; Formoterol: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and budesonide, a CYP3A4 substrate, may cause an increase in systemic concentrations of budesonide. Use caution when administering these drugs concomitantly.
    Budesonide; Glycopyrrolate; Formoterol: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and budesonide, a CYP3A4 substrate, may cause an increase in systemic concentrations of budesonide. Use caution when administering these drugs concomitantly.
    Bupivacaine Liposomal: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and bupivacaine, a CYP3A4 substrate, may cause an increase in systemic concentrations of bupivacaine. Use caution when administering these drugs concomitantly.
    Bupivacaine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and bupivacaine, a CYP3A4 substrate, may cause an increase in systemic concentrations of bupivacaine. Use caution when administering these drugs concomitantly.
    Bupivacaine; Epinephrine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and bupivacaine, a CYP3A4 substrate, may cause an increase in systemic concentrations of bupivacaine. Use caution when administering these drugs concomitantly.
    Bupivacaine; Lidocaine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and bupivacaine, a CYP3A4 substrate, may cause an increase in systemic concentrations of bupivacaine. Use caution when administering these drugs concomitantly. (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and lidocaine, a CYP3A4 substrate, may cause an increase in systemic concentrations of lidocaine. Use caution when administering these drugs concomitantly.
    Bupivacaine; Meloxicam: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and bupivacaine, a CYP3A4 substrate, may cause an increase in systemic concentrations of bupivacaine. Use caution when administering these drugs concomitantly. (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and meloxicam, a CYP3A4 substrate, may cause an increase in systemic concentrations of meloxicam. Use caution when administering these drugs concomitantly.
    Buprenorphine: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and buprenorphine have been reported to prolong the QT interval. If pazopanib and buprenorphine must be used, closely monitor the patient for QT prolongation. In addition, pazopanib is a weak inhibitor of and substrate for CYP3A4, and buprenorphine is a CYP3A4 substrate. Concurrent administration of buprenorphine and pazopanib may result in increased pazopanib concentrations and/or increased buprenorphine concentrations. Dose reduction of one or both medications should be considered when coadministration of pazopanib and buprenorphine is necessary.
    Buprenorphine; Naloxone: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and buprenorphine have been reported to prolong the QT interval. If pazopanib and buprenorphine must be used, closely monitor the patient for QT prolongation. In addition, pazopanib is a weak inhibitor of and substrate for CYP3A4, and buprenorphine is a CYP3A4 substrate. Concurrent administration of buprenorphine and pazopanib may result in increased pazopanib concentrations and/or increased buprenorphine concentrations. Dose reduction of one or both medications should be considered when coadministration of pazopanib and buprenorphine is necessary.
    Buspirone: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and buspirone, a CYP3A4 substrate, may cause an increase in systemic concentrations of buspirone. Use caution when administering these drugs concomitantly.
    Cabotegravir; Rilpivirine: (Major) Concurrent use of pazopanib and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be continued, closely monitor the patient for QT interval prolongation. Pazopanib has been reported to prolong the QT interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and rilpivirine, a CYP3A4 substrate, may cause an increase in systemic concentrations of rilpivirine.
    Cabozantinib: (Minor) Monitor for an increase in pazopanib-related adverse reactions if coadministration of with cabozantinib is necessary; a dose adjustment of pazopanib may be necessary. Pazopanib 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.
    Calcium Carbonate: (Moderate) Separate administration of pazopanib and antacids by several hours if coadministration is necessary in order to avoid a reduction in pazopanib exposure, which may decrease efficacy.
    Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) Avoid coadministration of pazopanib with H2-blockers due to decreased absorption of pazopanib, which may decrease efficacy. If concomitant administration with a gastric acid-reducing agent is unavoidable, consider the use of a short-acting antacid in place of an H2-blocker; separate administration of the short-acting antacid and pazopanib by several hours to avoid a reduction in pazopanib exposure. Concomitant use of pazopanib with a proton pump inhibitor decreased pazopanib exposure (AUC and Cmax) by approximately 40%. (Moderate) Separate administration of pazopanib and antacids by several hours if coadministration is necessary in order to avoid a reduction in pazopanib exposure, which may decrease efficacy.
    Calcium Carbonate; Magnesium Hydroxide: (Moderate) Separate administration of pazopanib and antacids by several hours if coadministration is necessary in order to avoid a reduction in pazopanib exposure, which may decrease efficacy.
    Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Separate administration of pazopanib and antacids by several hours if coadministration is necessary in order to avoid a reduction in pazopanib exposure, which may decrease efficacy.
    Calcium Carbonate; Risedronate: (Moderate) Separate administration of pazopanib and antacids by several hours if coadministration is necessary in order to avoid a reduction in pazopanib exposure, which may decrease efficacy.
    Calcium Carbonate; Simethicone: (Moderate) Separate administration of pazopanib and antacids by several hours if coadministration is necessary in order to avoid a reduction in pazopanib exposure, which may decrease efficacy.
    Calcium; Vitamin D: (Moderate) Separate administration of pazopanib and antacids by several hours if coadministration is necessary in order to avoid a reduction in pazopanib exposure, which may decrease efficacy.
    Cannabidiol: (Major) Avoid coadministration of pazopanib and cannabidiol due to the potential for increased pazopanib exposure. Pazopanib is a P-gp substrate; cannabidiol is a P-gp inhibitor. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit P-gp.
    Capmatinib: (Major) Avoid coadministration of pazopanib and capmatinib due to the potential for increased pazopanib exposure. Pazopanib is a P-glycoprotein (P-gp) and BCRP substrate. Capmatinib is a P-gp and BCRP inhibitor. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit P-gp or BCRP.
    Carbamazepine: (Major) Avoid administering pazopanib in patients who require chronic treatment with a strong CYP3A4 inducer, such as carbamazepine. The concomitant use of pazopanib, a weak CYP3A4 inhibitor and a substrate for CYP3A4 and P-glycoprotein (P-gp), and carbamazepine, a strong CYP3A4 inducer and a P-gp inducer, may result in altered pazopanib and/or carbamazepine concentrations.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like pazopanib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If pazopanib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like pazopanib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If pazopanib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Carvedilol: (Moderate) Altered concentrations of pazopanib and/or carvedilol may occur during coadministration. Carvedilol and pazopanib are both substrates and inhibitors of P-glycoprotein (P-gp). Use caution if concomitant use is necessary and monitor for increased side effects.
    Celecoxib; Tramadol: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and tramadol, a CYP3A4 substrate, may cause an increase in systemic concentrations of tramadol. Use caution when administering these drugs concomitantly.
    Ceritinib: (Major) Avoid coadministration of pazopanib and ceritinib due to the potential for increased pazopanib exposure; QT prolongation may also occur. If concurrent use is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. Closely monitor ECGs for QT prolongation; also monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Pazopanib is a CYP3A4 substrate that has been reported to prolong the QT interval. Ceritinib is a strong CYP3A4 inhibitor that has had reports of concentration-dependent QT prolongation. Concurrent use of another strong CYP3A4 inhibitor increased the Cmax and AUC of pazopanib by 1.5-fold and 1.7-fold, respectively.
    Chloramphenicol: (Moderate) Pazopanib is a substrate for CYP3A4. Chloramphenicol is an inhibitor of CYP3A4. Concurrent administration may result in increased pazopanib concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and chloramphenicol is required.
    Chlordiazepoxide; Amitriptyline: (Minor) Coadministration of pazopanib and other drugs that prolong the QT interval, such as tricyclic antidepressants is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Amitriptyline, clomipramine and imipramine are CYP3A4 substrates. Coadministration of pazopanib may cause an increase in systemic concentrations of the tricyclic antidepressant. Use caution when administering these drugs concomitantly.
    Chloroquine: (Major) Avoid coadministration of chloroquine with pazopanib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Pazopanib has also been reported to prolong the QT interval.
    Chlorpheniramine; Dextromethorphan: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with pazopanib may alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage adjustment of dihydrocodeine until stable drug effects are achieved. Discontinuation of pazopanib could alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If pazopanib is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Pazopanib is a weak inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase dihydrocodeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with pazopanib may alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage adjustment of dihydrocodeine until stable drug effects are achieved. Discontinuation of pazopanib could alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If pazopanib is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Pazopanib is a weak inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase dihydrocodeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like pazopanib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If pazopanib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Chlorpheniramine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like pazopanib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If pazopanib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like pazopanib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If pazopanib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like pazopanib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If pazopanib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Chlorpromazine: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval (e.g. chlorpromazine) is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and chlorpromazine must be continued, closely monitor the patient for QT interval prolongation.
    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.
    Cilostazol: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and cilostazol, a CYP3A4 substrate, may cause an increase in systemic concentrations of cilostazol. Use caution when administering these drugs concomitantly.
    Cimetidine: (Major) Avoid coadministration of pazopanib with H2-blockers due to decreased absorption of pazopanib, which may decrease efficacy. If concomitant administration with a gastric acid-reducing agent is unavoidable, consider the use of a short-acting antacid in place of an H2-blocker; separate administration of the short-acting antacid and pazopanib by several hours to avoid a reduction in pazopanib exposure. Concomitant use of pazopanib with a proton pump inhibitor decreased pazopanib exposure (AUC and Cmax) by approximately 40%.
    Cinacalcet: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and cinacalcet, a CYP3A4 substrate, may cause an increase in systemic concentrations of cinacalcet. Use caution when administering these drugs concomitantly.
    Ciprofloxacin: (Major) Concurrent use of pazopanib and ciprofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent use is required, closely monitor the patient for QT interval prolongation. Pazopanib has been reported to prolong the QT interval, and ciprofloxacin is associated with a possible risk for QT prolongation and TdP.
    Cisapride: (Contraindicated) Pazopanib has been reported to prolong the QT interval. Because of the potential for torsade de pointes (TdP), use of cisapride with pazopanib is contraindicated.
    Citalopram: (Major) Coadministration of pazopanib and other drugs that prolongs the QT interval, such as citalopram, is not advised; pazopanib has been reported to prolongs the QT interval. If pazopanib and the other drug must be continued, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and citalopram, a CYP3A4 substrate, may cause an increase in systemic concentrations of citalopram. Use caution if coadministration is necessary.
    Clarithromycin: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and clarithromycin have been reported to prolong the QT interval. If pazopanib and clarithromycin must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a substrate for CYP3A4 and P-glycoprotein (P-gp) and weak inhibitor of CYP3A4. Clarithromycin is a strong inhibitor of CYP3A4, an inhibitor of P-gp, and substrate of CYP3A4. Concurrent administration of clarithromycin and pazopanib may result in increased pazopanib and/or clarithromycin concentrations; avoid use of these agents together if possible. If co-administration of pazopanib and clarithromycin is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur.
    Clofazimine: (Major) Coadministration of clofazimine and pazopanib is not recommended due to the risk of additive QT prolongation and torsade de pointes (TdP). Monitor the ECG for QT prolongation if coadministration is required. QT prolongation and TdP have been reported in patients receiving clofazimine in combination with QT prolonging medications. Pazopanib is associated with QT interval prolongation.
    Clomipramine: (Minor) Coadministration of pazopanib and other drugs that prolong the QT interval, such as tricyclic antidepressants is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Amitriptyline, clomipramine and imipramine are CYP3A4 substrates. Coadministration of pazopanib may cause an increase in systemic concentrations of the tricyclic antidepressant. Use caution when administering these drugs concomitantly.
    Clonazepam: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and clonazepam, a CYP3A4 substrate, may cause an increase in systemic concentrations of clonazepam. Use caution when administering these drugs concomitantly.
    Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist. Additionally, in vitro studies have shown that pazopanib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Clozapine therapy may lead to S-T segment depression and flattening or inversion of T waves. In theory, concurrent use of pazopanib and clozapine could produce clinically significant prolongation of the QTc interval. Pazopanib is also a weak inhibitor of CYP3A4. Coadministration of pazopanib and clozapine, a CYP3A4 substrate, may cause an increase in systemic concentrations of clozapine. Elevated plasma concentrations of clozapine may increase the risk for QT prolongation, torsade de pointes (TdP), sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. According to the manufacturer, patients receiving clozapine in combination with an inhibitor of CYP3A4 should be monitored for adverse reactions. Consideration should be given to reducing the clozapine dose if necessary. If the inhibitor is discontinued after dose adjustments are made, monitor for lack of clozapine effectiveness and consider increasing the clozapine dose if necessary.
    Cobicistat: (Major) Avoid coadministration of pazopanib and cobicistat due to the potential for increased exposure of both pazopanib and cobicistat. If concurrent use is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. Pazopanib is an inhibitor and substrate of CYP3A4; cobicistat is a strong CYP3A4 inhibitor and a CYP3A4 substrate. Concurrent use of pazopanib another strong CYP3A4 inhibitor increased the Cmax and AUC of pazopanib by 1.5-fold and 1.7-fold, respectively. In addition, pazopanib is a substrate/inhibitor of P-glycoprotein (P-gp), an inhibitor of CYP2D6, and a substrate of breast cancer resistance protein (BCRP). Cobicistat is an inhibitor of P-gp, BCRP, and a substrate/inhibitor of CYP2D6.
    Cobimetinib: (Moderate) If concurrent use of cobimetinib and pazopanib is necessary, use caution and monitor for increased cobimetinib-related adverse effects. Cobimetinib is a CYP3A substrate in vitro as well as a P-glycoprotein (P-gp) substrate; pazopanib is a weak inhibitor of CYP3A and a moderate P-gp inhibitor. In healthy subjects (n = 15), coadministration of a single 10 mg dose of cobimetinib with itraconazole (200 mg once daily for 14 days), a strong CYP3A4 inhibitor, increased the mean cobimetinib AUC by 6.7-fold (90% CI, 5.6 to 8) and the mean Cmax by 3.2-fold (90% CI, 2.7 to 3.7). Simulations showed that predicted steady-state concentrations of cobimetinib at a reduced dose of 20 mg administered concurrently with short-term (less than 14 days) treatment of a moderate CYP3A inhibitor were similar to observed steady-state concentrations of cobimetinib 60 mg alone. The manufacturer of cobimetinib recommends avoiding coadministration with moderate to strong CYP3A inhibitors, and significantly reducing the dose of cobimetinib if coadministration with moderate CYP3A inhibitors cannot be avoided. Guidance is not available regarding concomitant use of cobimetinib with weak CYP3A inhibitors.
    Codeine; Phenylephrine; Promethazine: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as promethazine, is not advised; pazopanib and promethazine have been reported to prolong the QT interval. If pazopanib and promethazine must be continued, closely monitor the patient for QT interval prolongation.
    Codeine; Promethazine: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as promethazine, is not advised; pazopanib and promethazine have been reported to prolong the QT interval. If pazopanib and promethazine must be continued, closely monitor the patient for QT interval prolongation.
    Colchicine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and colchicine, a CYP3A4 substrate, may cause an increase in systemic concentrations of colchicine. Use caution when administering these drugs concomitantly.
    Conivaptan: (Major) Avoid coadministration of pazopanib and conivaptan due to the potential for increased pazopanib exposure. Pazopanib is a P-gp substrate; conivaptan is a P-gp inhibitor. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit P-gp.
    Crizotinib: (Major) Avoid coadministration of crizotinib with pazopanib due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Pazopanib has also been reported to prolong the QT interval.
    Cyclosporine: (Major) Avoid administering pazopanib with strong breast cancer resistance protein (BCRP) inhibitors, such as cyclosporine. The concomitant use of pazopanib, a weak CYP3A4 inhibitor and a CYP3A4, P-glycoprotein (P-gp), and BCRP substrate, and cyclosporine, a CYP3A4, P-gp, and BCRP inhibitor and CYP3A4 substrate, may result in altered pazopanib and/or cyclosporine concentrations.
    Daclatasvir: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with pazopanib, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. In addition, the therapeutic effects of pazopanib, a substrate for P-glycoprotein (P-gp) and the breast cancer resistant protein (BCRP), may be increased by daclatasvir, a P-gp and BCRP inhibitor. If these drugs are administered together, monitor patients for adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
    Danazol: (Moderate) Pazopanib is a substrate for CYP3A4. Danazol is an inhibitor of CYP3A4. Concurrent administration may result in increased pazopanib concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and danazol is required.
    Dapsone: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and dapsone, a CYP3A4 substrate, may cause an increase in systemic concentrations of dapsone. Use caution when administering these drugs concomitantly.
    Darifenacin: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and darifenacin, a CYP3A4 substrate, may cause an increase in systemic concentrations of darifenacin. Use caution when administering these drugs concomitantly.
    Darolutamide: (Major) Avoid coadministration of pazopanib and darolutamide due to the potential for increased pazopanib exposure. Pazopanib is a BCRP substrate; darolutamide is a BCRP inhibitor. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit BCRP.
    Darunavir: (Major) Avoid coadministration of pazopanib and darunavir due to the potential for increased pazopanib exposure. If concurrent use is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. Pazopanib is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. Concurrent use of another strong CYP3A4 inhibitor increased the Cmax and AUC of pazopanib by 1.5-fold and 1.7-fold, respectively.
    Darunavir; Cobicistat: (Major) Avoid coadministration of pazopanib and cobicistat due to the potential for increased exposure of both pazopanib and cobicistat. If concurrent use is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. Pazopanib is an inhibitor and substrate of CYP3A4; cobicistat is a strong CYP3A4 inhibitor and a CYP3A4 substrate. Concurrent use of pazopanib another strong CYP3A4 inhibitor increased the Cmax and AUC of pazopanib by 1.5-fold and 1.7-fold, respectively. In addition, pazopanib is a substrate/inhibitor of P-glycoprotein (P-gp), an inhibitor of CYP2D6, and a substrate of breast cancer resistance protein (BCRP). Cobicistat is an inhibitor of P-gp, BCRP, and a substrate/inhibitor of CYP2D6. (Major) Avoid coadministration of pazopanib and darunavir due to the potential for increased pazopanib exposure. If concurrent use is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. Pazopanib is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. Concurrent use of another strong CYP3A4 inhibitor increased the Cmax and AUC of pazopanib by 1.5-fold and 1.7-fold, respectively.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid coadministration of pazopanib and cobicistat due to the potential for increased exposure of both pazopanib and cobicistat. If concurrent use is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. Pazopanib is an inhibitor and substrate of CYP3A4; cobicistat is a strong CYP3A4 inhibitor and a CYP3A4 substrate. Concurrent use of pazopanib another strong CYP3A4 inhibitor increased the Cmax and AUC of pazopanib by 1.5-fold and 1.7-fold, respectively. In addition, pazopanib is a substrate/inhibitor of P-glycoprotein (P-gp), an inhibitor of CYP2D6, and a substrate of breast cancer resistance protein (BCRP). Cobicistat is an inhibitor of P-gp, BCRP, and a substrate/inhibitor of CYP2D6. (Major) Avoid coadministration of pazopanib and darunavir due to the potential for increased pazopanib exposure. If concurrent use is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. Pazopanib is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. Concurrent use of another strong CYP3A4 inhibitor increased the Cmax and AUC of pazopanib by 1.5-fold and 1.7-fold, respectively.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid coadministration of pazopanib and ritonavir due to the potential for increased pazopanib exposure. If concurrent use is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. Pazopanib is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. Concurrent use of another strong CYP3A4 inhibitor increased the Cmax and AUC of pazopanib by 1.5-fold and 1.7-fold, respectively. (Major) Avoid concurrent administration of pazopanib with dasabuvir; ombitasvir; paritaprevir; ritonavir if possibile. Complex metabolic interactions may occur resulting in elevated plasma concentrations of all 5 drugs. If coadministration is unavoidable, reduce the pazopanib dosage to 400 mg PO once daily, and monitor for adverse effects. Further dosage adjustments may be necessary depending on tolerability. Both pazopanib and ritonavir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. Paritaprevir and dasabuvir (minor) are also CYP3A4 substrates. Pazopanib inhibits CYP2D6 and CYP2C8; dasabuvir is primarily metabolized by CYP2C8 and CYP2D6 is partially responsible for the metabolism of ritonavir. Pazopanib is a substrate for the breast cancer resistance protein (BCRP); ritonavir, dasabuvir, paritaprevir are BCRP inhibitors. Finally, pazopanib is a substrate and inhibitor of the drug transporter P-glycoprotein (P-gp); dasabuvir, ombitasvir, paritaprevir and ritonavir are all substrates of P-gp. Ritonavir is also a P-gp inhibitor.
    Degarelix: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval like degarelix is not advised. If concomitant use is unavoidable, closely monitor the patient for QT interval prolongation. Pazopanib has been reported to prolong the QT interval. Androgen deprivation therapy (i.e., degarelix) may also prolong the QT/QTc interval.
    Delavirdine: (Major) Avoid administering pazopanib with strong CYP3A4 inhibitors, such as delavirdine. If co-administration with a strong CYP3A4 inhibitor is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. The concomitant use of pazopanib, a weak CYP3A4 inhibitor and a CYP3A4 substrate, and delavirdine, a strong CYP3A4 inhibitor and CYP3A4 substrate, may result in altered pazopanib and/or delavirdine concentrations.
    Desflurane: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be avoided with pazopanib include halogenated anesthetics.
    Desipramine: (Minor) Coadministration of pazopanib and other drugs that prolong the QT interval, such as tricyclic antidepressants is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Amitriptyline, clomipramine and imipramine are CYP3A4 substrates. Coadministration of pazopanib may cause an increase in systemic concentrations of the tricyclic antidepressant. Use caution when administering these drugs concomitantly.
    Desogestrel; Ethinyl Estradiol: (Moderate) Pazopanib is a substrate for CYP3A4. Ethinyl estradiol is an inhibitor of CYP3A4. Concurrent administration may result in increased pazopanib concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and ethinyl estradiol is required.
    Deutetrabenazine: (Major) Avoid coadministration of deutetrabenazine with pazopanib due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia, hypomagnesemia, and hypocalcemia. Pazopanib has been associated with QT prolongation. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
    Dexamethasone: (Major) Avoid administering pazopanib in patients who require chronic treatment with a strong CYP3A4 inducer, such as dexamethasone. The concomitant use of pazopanib, a weak CYP3A4 inhibitor and a substrate for CYP3A4 and P-glycoprotein (P-gp), and dexamethasone, a strong CYP3A4 inducer and a CYP3A4and P-gp substrate, may result in altered pazopanib and/or dexamethasone concentrations. In addition, because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with antineoplastic agents. While therapy is designed to take advantage of this effect, patients may be predisposed to over-immunosuppression resulting in an increased risk for the development of severe infections. Close clinical monitoring is advised with concurrent use; in the presence of serious infections, continuation of the corticosteroid or immunosuppressive agent may be necessary but should be accompanied by appropriate antimicrobial therapies as indicated.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Dexlansoprazole: (Major) Pazopanib displays pH-dependent solubility with decreased solubility at a higher pH. The concomitant use of pazopanib and proton pump inhibitors (PPIs) that elevate the gastric pH may reduce the bioavailability of pazopanib. In a study of patients with solid tumors, the AUC and Cmax of pazopanib were decreased by approximately 40% when coadministered with esomeprazole. If a drug is needed to raise the gastric pH, consider use of a short-acting antacid; separate antacid and pazopanib dosing by several hours.
    Dextromethorphan: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Dextromethorphan; Guaifenesin: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Dextromethorphan; Quinidine: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and quinidine (including dextromethorphan; quinidine have been reported to prolong the QT interval. If pazopanib and quinidine must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4 and a substrate for P-glycoprotein (P-gp). Quinidine is a substrate for CYP3A4 and an inhibitor of P-gp. Concurrent administration of quinidine and pazopanib may result in increased pazopanib and/or quinidine concentrations. Use caution when concurrent administration is necessary. (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Diazepam: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and diazepam, a CYP3A4 substrate, may cause an increase in systemic concentrations of diazepam. Use caution when administering these drugs concomitantly.
    Diclofenac: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and diclofenac, a CYP3A4 substrate, may cause an increase in systemic concentrations of diclofenac. Use caution when administering these drugs concomitantly.
    Diclofenac; Misoprostol: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and diclofenac, a CYP3A4 substrate, may cause an increase in systemic concentrations of diclofenac. Use caution when administering these drugs concomitantly.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with pazopanib may alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage adjustment of dihydrocodeine until stable drug effects are achieved. Discontinuation of pazopanib could alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If pazopanib is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Pazopanib is a weak inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase dihydrocodeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like pazopanib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If pazopanib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Disopyramide: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. Disopyramide is established to have a causal association with QT prolongation and TdP (torsade de pointe). If pazopanib and disopyramide must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and disopyramide, a CYP3A4 substrate, may cause an increase in systemic concentrations of disopyramide. Use caution when concurrent administration of disopyramide and pazopanib is necessary.
    Disulfiram: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and disulfiram, a CYP3A4 substrate, may cause an increase in systemic concentrations of disulfiram. Use caution when administering these drugs concomitantly.
    Docetaxel: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and docetaxel, a CYP3A4 substrate, may cause an increase in systemic concentrations of docetaxel. Use caution when administering these drugs concomitantly.
    Dofetilide: (Major) Coadministration of dofetilide and pazopanib is not recommended as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, closely monitor the patient for QT interval prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Pazopanib has been reported to prolong the QT interval.
    Dolasetron: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), dolasetron and pazopanib should be used together cautiously. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has also been reported to prolong the QT interval.
    Dolutegravir; Rilpivirine: (Major) Concurrent use of pazopanib and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be continued, closely monitor the patient for QT interval prolongation. Pazopanib has been reported to prolong the QT interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and rilpivirine, a CYP3A4 substrate, may cause an increase in systemic concentrations of rilpivirine.
    Donepezil: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Pazopanib has a possible risk for QT prolongation and TdP and should be used cautiously and with close monitoring with donepezil. In addition, pazopanib is a weak inhibitor of CYP3A4, and coadministration of pazopanib and donepezil, a CYP3A4 substrate, may cause an increase in systemic concentrations of donepezil. Use caution when administering these drugs concomitantly.
    Donepezil; Memantine: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Pazopanib has a possible risk for QT prolongation and TdP and should be used cautiously and with close monitoring with donepezil. In addition, pazopanib is a weak inhibitor of CYP3A4, and coadministration of pazopanib and donepezil, a CYP3A4 substrate, may cause an increase in systemic concentrations of donepezil. Use caution when administering these drugs concomitantly.
    Doxepin: (Minor) Coadministration of pazopanib and other drugs that prolong the QT interval, such as tricyclic antidepressants is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Amitriptyline, clomipramine and imipramine are CYP3A4 substrates. Coadministration of pazopanib may cause an increase in systemic concentrations of the tricyclic antidepressant. Use caution when administering these drugs concomitantly.
    Doxorubicin Liposomal: (Major) Avoid coadministration of pazopanib with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Pazopanib is a CYP2D6 and CYP3A4 inhibitor; doxorubicin is a major substrate of CYP2D6 and CYP3A4. Concurrent use of CYP2D6 or CYP3A4 inhibitors with doxorubicin has resulted in clinically significant interactions.
    Doxorubicin: (Major) Avoid coadministration of pazopanib with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Pazopanib is a CYP2D6 and CYP3A4 inhibitor; doxorubicin is a major substrate of CYP2D6 and CYP3A4. Concurrent use of CYP2D6 or CYP3A4 inhibitors with doxorubicin has resulted in clinically significant interactions.
    Dronabinol: (Moderate) Use caution if coadministration of dronabinol with pazopanib is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; pazopanib is a weak inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Dronedarone: (Contraindicated) Concurrent use of pazopanib and dronedarone is contraindicated. Pazopanib has been reported to prolong the QT interval. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
    Droperidol: (Major) Coadministration of pazopanib and other drugs that prolongs the QT interval is not advised; pazopanib has been reported to prolongs the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). If pazopanib and droperidol must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and droperidol, a CYP3A4 substrate, may cause an increase in systemic concentrations of droperidol. Use caution when concurrent administration of droperidol and pazopanib is necessary.
    Drospirenone; Ethinyl Estradiol: (Moderate) Pazopanib is a substrate for CYP3A4. Ethinyl estradiol is an inhibitor of CYP3A4. Concurrent administration may result in increased pazopanib concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and ethinyl estradiol is required.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Pazopanib is a substrate for CYP3A4. Ethinyl estradiol is an inhibitor of CYP3A4. Concurrent administration may result in increased pazopanib concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and ethinyl estradiol is required.
    Dutasteride; Tamsulosin: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and tamsulosin, a CYP3A4 substrate, may cause an increase in systemic concentrations of tamsulosin. Use caution when administering these drugs concomitantly.
    Edoxaban: (Moderate) Coadministration of edoxaban and pazopanib may result in increased concentrations of edoxaban. Edoxaban is a P-glycoprotein (P-gp) substrate and pazopanib is a P-gp inhibitor. Increased concentrations of edoxaban may occur during concomitant use of pazopanib; monitor for increased adverse effects of edoxaban. Dosage reduction may be considered for patients being treated for deep venous thrombosis (DVT) or pulmonary embolism.
    Efavirenz: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as efavirenz, is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. In addition, concurrent use may increase the systemic concentration of efavirenz and decrease the concentration of pazopanib. Efavirenz is a CYP3A4 substrate and inducer, while pazopanib is a CYP3A4 substrate and mild inhibitor.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as efavirenz, is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. In addition, concurrent use may increase the systemic concentration of efavirenz and decrease the concentration of pazopanib. Efavirenz is a CYP3A4 substrate and inducer, while pazopanib is a CYP3A4 substrate and mild inhibitor.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as efavirenz, is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. In addition, concurrent use may increase the systemic concentration of efavirenz and decrease the concentration of pazopanib. Efavirenz is a CYP3A4 substrate and inducer, while pazopanib is a CYP3A4 substrate and mild inhibitor.
    Elbasvir; Grazoprevir: (Moderate) Administering elbasvir; grazoprevir with pazopanib may cause the plasma concentrations of all three drugs to increase; thereby increasing the potential for adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Pazopanib is a substrate and mild inhibitor of CYP3A. Both elbasvir and grazoprevir are metabolized by CYP3A, and grazoprevir is also a weak CYP3A inhibitor. In addition, pazopanib is a substrate for the breast cancer resistance protein (BCRP), while both elbasvir and grazoprevir are BCRP inhibitors. If these drugs are used together, closely monitor for signs of hepatotoxicity.
    Eletriptan: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and eletriptan, a CYP3A4 substrate, may cause an increase in systemic concentrations of eletriptan. Use caution when administering these drugs concomitantly.
    Eliglustat: (Major) Coadministration of pazopanib and eliglustat is not recommended. Eliglustat is a CYP2D6 and CYP3A4 substrate predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations; it is also a P-glycoprotein (P-gp) inhibitor. Pazopanib is a weak inhibitor of CYP3A4 and CYP2D6 in vivo and a P-gp substrate in vitro; it can also independently prolong the QT interval. Coadministration of eliglustat and pazopanib may result in additive effects on the QT interval and, potentially, increased plasma concentrations of both drugs, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias).
    Eltrombopag: (Major) Avoid administering pazopanib with strong breast cancer resistance protein (BCRP) inhibitors, such as eltrombopag. The concomitant use of pazopanib, a BCRP substrate,and eltrombopag, a BCRP inhibitor, may result in increased pazopanib concentrations.
    Elvitegravir: (Major) Caution is warranted when elvitegravir is administered with pazopanib as there is a potential for elevated concentrations of both drugs. Both drugs are substrates and inhibitors of CYP3A4.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid coadministration of pazopanib and cobicistat due to the potential for increased exposure of both pazopanib and cobicistat. If concurrent use is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. Pazopanib is an inhibitor and substrate of CYP3A4; cobicistat is a strong CYP3A4 inhibitor and a CYP3A4 substrate. Concurrent use of pazopanib another strong CYP3A4 inhibitor increased the Cmax and AUC of pazopanib by 1.5-fold and 1.7-fold, respectively. In addition, pazopanib is a substrate/inhibitor of P-glycoprotein (P-gp), an inhibitor of CYP2D6, and a substrate of breast cancer resistance protein (BCRP). Cobicistat is an inhibitor of P-gp, BCRP, and a substrate/inhibitor of CYP2D6. (Major) Caution is warranted when elvitegravir is administered with pazopanib as there is a potential for elevated concentrations of both drugs. Both drugs are substrates and inhibitors of CYP3A4.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of pazopanib and cobicistat due to the potential for increased exposure of both pazopanib and cobicistat. If concurrent use is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. Pazopanib is an inhibitor and substrate of CYP3A4; cobicistat is a strong CYP3A4 inhibitor and a CYP3A4 substrate. Concurrent use of pazopanib another strong CYP3A4 inhibitor increased the Cmax and AUC of pazopanib by 1.5-fold and 1.7-fold, respectively. In addition, pazopanib is a substrate/inhibitor of P-glycoprotein (P-gp), an inhibitor of CYP2D6, and a substrate of breast cancer resistance protein (BCRP). Cobicistat is an inhibitor of P-gp, BCRP, and a substrate/inhibitor of CYP2D6. (Major) Caution is warranted when elvitegravir is administered with pazopanib as there is a potential for elevated concentrations of both drugs. Both drugs are substrates and inhibitors of CYP3A4.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Concurrent use of pazopanib and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be continued, closely monitor the patient for QT interval prolongation. Pazopanib has been reported to prolong the QT interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and rilpivirine, a CYP3A4 substrate, may cause an increase in systemic concentrations of rilpivirine.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Concurrent use of pazopanib and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be continued, closely monitor the patient for QT interval prolongation. Pazopanib has been reported to prolong the QT interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and rilpivirine, a CYP3A4 substrate, may cause an increase in systemic concentrations of rilpivirine.
    Enalapril; Felodipine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and felodipine, a CYP3A4 substrate, may cause an increase in systemic concentrations of felodipine. Use caution when administering these drugs concomitantly.
    Enasidenib: (Major) Avoid coadministration of pazopanib and enasidenib due to the potential for increased pazopanib exposure. Pazopanib is a P-gp and BCRP substrate; enasidenib is a P-gp and BCRP inhibitor. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit P-gp or BCRP.
    Encorafenib: (Major) Avoid coadministration of encorafenib and pazopanib due to the potential for additive QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Pazopanib has been reported to prolong the QT interval.
    Enflurane: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be avoided with pazopanib include halogenated anesthetics.
    Entrectinib: (Major) Avoid coadministration of entrectinib with pazopanib due to the risk of QT prolongation. If coadministration cannot be avoided, closely monitor the patient for QT interval prolongation. Entrectinib has been associated with QT prolongation. Pazopanib has also been reported to prolong the QT interval.
    Enzalutamide: (Major) Avoid coadministration of pazopanib with enzalutamide due to the potential for decreased plasma concentrations of pazopanib. Pazopanib is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer.
    Ergotamine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and ergotamine, a CYP3A4 substrate, may cause an increase in systemic concentrations of ergotamine. Use caution when administering these drugs concomitantly.
    Ergotamine; Caffeine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and ergotamine, a CYP3A4 substrate, may cause an increase in systemic concentrations of ergotamine. Use caution when administering these drugs concomitantly.
    Eribulin: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as eribulin, is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and eribulin must be continued, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Erythromycin: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as erythromycin, is not advised. Pazopanib and erythromycin have been reported to prolong the QT interval. If pazopanib and erythromycin must be continued, closely monitor the patient for QT interval prolongation.
    Erythromycin; Sulfisoxazole: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as erythromycin, is not advised. Pazopanib and erythromycin have been reported to prolong the QT interval. If pazopanib and erythromycin must be continued, closely monitor the patient for QT interval prolongation.
    Escitalopram: (Major) Because both pazopanib and escitalopram are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and escitalopram, a CYP3A4 substrate, may cause an increase in systemic concentrations of escitalopram. Use caution when administering these drugs concomitantly.
    Esomeprazole: (Major) Pazopanib displays pH-dependent solubility with decreased solubility at a higher pH. The concomitant use of pazopanib and proton pump inhibitors (PPIs) that elevate the gastric pH may reduce the bioavailability of pazopanib. In a study of patients with solid tumors, the AUC and Cmax of pazopanib were decreased by approximately 40% when coadministered with esomeprazole. If a drug is needed to raise the gastric pH, consider use of a short-acting antacid; separate antacid and pazopanib dosing by several hours.
    Estazolam: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and estazolam, a CYP3A4 substrate, may cause an increase in systemic concentrations of estazolam. Use caution when administering these drugs concomitantly.
    Eszopiclone: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and eszopiclone, a CYP3A4 substrate, may cause an increase in systemic concentrations of eszopiclone. Use caution when administering these drugs concomitantly.
    Ethinyl Estradiol: (Moderate) Pazopanib is a substrate for CYP3A4. Ethinyl estradiol is an inhibitor of CYP3A4. Concurrent administration may result in increased pazopanib concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and ethinyl estradiol is required.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) Pazopanib is a substrate for CYP3A4. Ethinyl estradiol is an inhibitor of CYP3A4. Concurrent administration may result in increased pazopanib concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and ethinyl estradiol is required.
    Ethinyl Estradiol; Norelgestromin: (Moderate) Pazopanib is a substrate for CYP3A4. Ethinyl estradiol is an inhibitor of CYP3A4. Concurrent administration may result in increased pazopanib concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and ethinyl estradiol is required.
    Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Pazopanib is a substrate for CYP3A4. Ethinyl estradiol is an inhibitor of CYP3A4. Concurrent administration may result in increased pazopanib concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and ethinyl estradiol is required.
    Ethinyl Estradiol; Norgestrel: (Moderate) Pazopanib is a substrate for CYP3A4. Ethinyl estradiol is an inhibitor of CYP3A4. Concurrent administration may result in increased pazopanib concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and ethinyl estradiol is required.
    Ethosuximide: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and ethosuximide, a CYP3A4 substrate, may cause an increase in systemic concentrations of ethosuximide. Use caution when administering these drugs concomitantly.
    Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) Pazopanib is a substrate for CYP3A4. Ethinyl estradiol is an inhibitor of CYP3A4. Concurrent administration may result in increased pazopanib concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and ethinyl estradiol is required.
    Etonogestrel; Ethinyl Estradiol: (Moderate) Pazopanib is a substrate for CYP3A4. Ethinyl estradiol is an inhibitor of CYP3A4. Concurrent administration may result in increased pazopanib concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and ethinyl estradiol is required.
    Etravirine: (Moderate) Pazopanib is a substrate for and a weak inhibitor of CYP3A4. Coadministration of pazopanib and etravirine, a CYP3A4 substrate, may cause an increase in systemic concentrations of etravirine. In addition, etravirine is an inducer of CYP3A4 and may cause a decrease in systemic concentrations of pazopanib. Use caution when administering these drugs concomitantly.
    Ezetimibe; Simvastatin: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and simvastatin, a CYP3A4 substrate, may cause an increase in systemic concentrations of simvastatin. Use caution when administering these drugs concomitantly.
    Ezogabine: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be avoided with pazopanib include ezogabine. If coadministration is necessary, the manufacturer of ezogabine recommends caution.
    Famotidine: (Major) Avoid coadministration of pazopanib with H2-blockers due to decreased absorption of pazopanib, which may decrease efficacy. If concomitant administration with a gastric acid-reducing agent is unavoidable, consider the use of a short-acting antacid in place of an H2-blocker; separate administration of the short-acting antacid and pazopanib by several hours to avoid a reduction in pazopanib exposure. Concomitant use of pazopanib with a proton pump inhibitor decreased pazopanib exposure (AUC and Cmax) by approximately 40%.
    Famotidine; Ibuprofen: (Major) Avoid coadministration of pazopanib with H2-blockers due to decreased absorption of pazopanib, which may decrease efficacy. If concomitant administration with a gastric acid-reducing agent is unavoidable, consider the use of a short-acting antacid in place of an H2-blocker; separate administration of the short-acting antacid and pazopanib by several hours to avoid a reduction in pazopanib exposure. Concomitant use of pazopanib with a proton pump inhibitor decreased pazopanib exposure (AUC and Cmax) by approximately 40%.
    Felodipine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and felodipine, a CYP3A4 substrate, may cause an increase in systemic concentrations of felodipine. Use caution when administering these drugs concomitantly.
    Fentanyl: (Moderate) Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. If pazopanib is discontinued, consider increasing the fentanyl dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Fentanyl is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like pazopanib can increase fentanyl exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of fentanyl. If pazopanib is discontinued, fentanyl plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to fentanyl.
    Finerenone: (Moderate) Monitor serum potassium during initiation or dose adjustment of either finerenone or pazopanib; a finerenone dosage reduction may be necessary. Concomitant use may increase finerenone exposure and the risk of hyperkalemia. Finerenone is a CYP3A substrate and pazopanib is a weak CYP3A inhibitor. Coadministration with another weak CYP3A inhibitor increased overall exposure to finerenone by 21%.
    Fingolimod: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as fingolimod, is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and fingolimod must be continued, closely monitor the patient for QT interval prolongation. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of torsade de pointes (TdP). Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
    Flecainide: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be avoided with pazopanib include flecainide.
    Flibanserin: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including pazopanib, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the risks of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
    Fluconazole: (Contraindicated) Due to the risk of life-threatening arrhythmias such as torsade de pointes (TdP), coadministration of fluconazole with drugs that both prolong the QT interval and are CYP3A4 substrates, like pazopanib, is contraindicated. Fluconazole has been associated with QT prolongation and rare cases of TdP. Additonally, fluconazole is an inhibitor of CYP3A4. Coadministration may result in elevated plasma concentrations of pazopanib, causing an increased risk for adverse events such as QT prolongation.
    Fluoxetine: (Major) Coadministration of fluoxetine and pazopanib is not recommended due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Pazopanib is associated with QT interval prolongation. QT prolongation and TdP have been reported in patients treated with fluoxetine.
    Fluphenazine: (Minor) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation that should be avoided with pazopanib include fluphenazine.
    Flurazepam: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and flurazepam, a CYP3A4 substrate, may cause an increase in systemic concentrations of flurazepam. Use caution when administering these drugs concomitantly.
    Flutamide: (Moderate) Pazopanib is a substrate for and a weak inhibitor of CYP3A4. Coadministration of pazopanib and flutamide, a CYP3A4 substrate, may cause an increase in systemic concentrations of flutamide. In addition, flutamide is an inducer of CYP3A4 and may cause a decrease in systemic concentrations of pazopanib. Use caution when administering these drugs concomitantly.
    Fluvoxamine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and pazopanib. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. Coadministration of pazopanib and other drugs that prolong the QT interval is not advised. If pazopanib and fluvoxamine must be coadministered, closely monitor for QT prolongation.
    Fosamprenavir: (Major) Avoid administering pazopanib with strong CYP3A4 inhibitors, such as amprenavir or fosamprenavir. If co-administration with a strong CYP3A4 inhibitor is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. The concomitant use of pazopanib, a weak CYP3A4 inhibitor and a substrate for CYP3A4, and fosamprenavir, an inhibitor, an inducer, and a substrate of CYP3A4, may result in altered pazopanib and/or fosamprenavir concentrations.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as pazopanib. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Pazopanib has also been reported to prolong the QT interval. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Fostamatinib: (Moderate) Monitor for pazopanib toxicities that may require pazopanib dose reduction if given concurrently with fostamatinib. Concomitant use of fostamatinib with a BCRP or P-gp substrate may increase the concentration of the BCRP or P-gp substrate. Fostamatinib is a P-gp inhibitor, and the active metabolite of fostamatinib, R406, is a BCRP inhibitor; pazopanib is a substrate for BCRP and P-gp. Coadministration of fostamatinib with another BCRP substrate increased the substrate AUC by 95% and Cmax by 88%. Coadministration of fostamatinib with another P-gp substrate increased the substrate AUC by 37% and Cmax by 70%.
    Fostemsavir: (Major) Avoid concomitant use of pazopanib and fostemsavir due to the potential for increased pazopanib exposure. Pazopanib is a BCRP substrate; fostemsavir is a BCRP inhibitor. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit BCRP.
    Gemifloxacin: (Major) Concurrent use of pazopanib and gemifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If coadministration is required, closely monitor the patient for QT interval prolongation. Pazopanib has been reported to prolong the QT interval. Gemifloxacin may also prolong the QT interval in some patients, with the maximal change in the QTc interval occurring approximately 5 to 10 hours following oral administration. The likelihood of QTc prolongation may increase with increasing dose of gemifloxacin; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
    Gemtuzumab Ozogamicin: (Major) Avoid coadministration of gemtuzumab ozogamicin with pazopanib due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Pazopanib has been reported to prolong the QT interval.
    Gilteritinib: (Major) Concomitant use of pazopanib with gilteritinib is not advised due to the potential for additive QT prolongation. If use together is necessary, closely monitor the patient.Taking these medication together may increase pazopanib exposure. Pazopanib is a P-gp and BCRP substrate; gilteritinib is a P-gp and BCRP inhibitor.
    Glasdegib: (Major) Coadministration of glasdegib with pazopanib is not advised due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Pazopanib has been reported to prolong the QT interval. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia.
    Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and pazopanib as coadministration may increase serum concentrations of pazopanib and increase the risk of adverse effects. Pazopanib is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); glecaprevir is an inhibitor of P-gp and BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and pazopanib as coadministration may increase serum concentrations of pazopanib and increase the risk of adverse effects. Pazopanib is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); pibrentasvir is an inhibitor of P-gp and BCRP.
    Glimepiride; Rosiglitazone: (Moderate) Pazopanib is a weak inhibitor of CYP2C8. Coadministration of pazopanib and rosiglitazone, a CYP2C8 substrate, may cause an increase in systemic concentrations of rosiglitazone. Use caution when administering these drugs concomitantly.
    Goserelin: (Major) Coadministration of pazopanib and goserelin is not advised due to the risk of QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT interval prolongation. Pazopanib has been reported to prolong the QT interval. Androgen deprivation therapy (i.e., goserelin) may also prolong the QT/QTc interval.
    Granisetron: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and granisetron have been reported to prolong the QT interval. If pazopanib and granisetron must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and granisetron, a CYP3A4 substrate, may cause an increase in systemic concentrations of granisetron. Use caution when concurrent administration of granisetron and pazopanib is necessary.
    Grapefruit juice: (Major) Avoid grapefruit juice during pazopanib treatment. Increased pazopanib serum concentrations may occur if grapefruit or grapefruit juice is consumed, possibly resulting in torsade de pointes and/or myelotoxicity. Pazopanib is a substrate for CYP3A4. Grapefruit juice inhibits the cytochrome P-450 3A4 isozyme in the gut wall. Grapefruit juice contains furanocoumarins that are metabolized by CYP3A4 to reactive intermediates. These intermediates form a covalent bond to the active site of the CYP3A4 enzyme, causing irreversible inactivation (mechanism-based inhibition). Consequently, CYP3A4 activity in the gut wall is inhibited until de novo synthesis returns the enzyme to its previous level.
    Guaifenesin; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like pazopanib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If pazopanib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like pazopanib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If pazopanib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    H2-blockers: (Major) Avoid coadministration of pazopanib with H2-blockers due to decreased absorption of pazopanib, which may decrease efficacy. If concomitant administration with a gastric acid-reducing agent is unavoidable, consider the use of a short-acting antacid in place of an H2-blocker; separate administration of the short-acting antacid and pazopanib by several hours to avoid a reduction in pazopanib exposure. Concomitant use of pazopanib with a proton pump inhibitor decreased pazopanib exposure (AUC and Cmax) by approximately 40%.
    Halogenated Anesthetics: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be avoided with pazopanib include halogenated anesthetics.
    Haloperidol: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. If pazopanib and haloperidol must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and haloperidol, a CYP3A4 substrate, may cause an increase in systemic concentrations of haloperidol. Use caution when concurrent administration of haloperidol and pazopanib is necessary.
    Halothane: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be avoided with pazopanib include halogenated anesthetics.
    Histrelin: (Major) Coadministration of pazopanib and histrelin is not advised due to the risk of QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT interval prolongation. Pazopanib has been reported to prolong the QT interval. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval.
    Homatropine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like pazopanib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If pazopanib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like pazopanib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If pazopanib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Hydrocodone; Ibuprofen: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like pazopanib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If pazopanib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Hydrocodone; Phenylephrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like pazopanib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If pazopanib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like pazopanib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If pazopanib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like pazopanib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If pazopanib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like pazopanib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If pazopanib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
    Hydroxychloroquine: (Major) Avoid coadministration of pazopanib and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine and pazopanib both prolong the QT interval.
    Hydroxyzine: (Major) Coadministration of hydroxyzine and pazopanib is not recommended due to the risk of additive QT prolongation and torsade de pointes (TdP). Monitor the ECG for QT prolongation if coadministration is required. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Pazopanib is associated with QT interval prolongation.
    Ibrutinib: (Moderate) Use ibrutinib and pazopanib together with caution; plasma concentrations of ibrutinib or pazopanib may be increased. Monitor patients for symptoms of ibrutinib or pazopanib toxicity if these agents are used together. Ibrutinib is a 3A4 substrate and a P-glycoprotein (P-gp) inhibitor and breast cancer resistance protein (BCRP) inhibitor in vitro; pazopanib is a weak 3A4 inhibitor and a P-gp and BCRP substrate.
    Ibuprofen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. If pazopanib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a weak inhibitor like pazopanib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If pazopanib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
    Ibutilide: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as ibutilide, is not advised; pazopanib has been reported to prolong the QT interval. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. If pazopanib and ibutilide must be continued, closely monitor the patient for QT interval prolongation.
    Iloperidone: (Major) Avoid coadministration of iloperidone and pazopanib; both drugs prolong the QT interval. If coadministration cannot be avoided, closely monitor the patient for QT interval prolongation.
    Imatinib: (Moderate) Pazopanib is a weak inhibitor of and substrate for CYP3A4. Imatinib is an inhibitor of and substrate for CYP3A4. Concurrent administration may result in increased pazopanib concentrations and/or increased imatinib, STI-571 concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and imatinib is required.
    Imipramine: (Minor) Coadministration of pazopanib and other drugs that prolong the QT interval, such as tricyclic antidepressants is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Amitriptyline, clomipramine and imipramine are CYP3A4 substrates. Coadministration of pazopanib may cause an increase in systemic concentrations of the tricyclic antidepressant. Use caution when administering these drugs concomitantly.
    Indinavir: (Major) Avoid administering pazopanib with strong CYP3A4 inhibitors, such as indinavir. If co-administration with a strong CYP3A4 inhibitor is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. The concomitant use of pazopanib, a weak CYP3A4 inhibitor and a CYP3A4 substrate, and indinavir, a strong CYP3A4 inhibitor and CYP3A4 substrate, may result in altered pazopanib and/or indinavir concentrations.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with pazopanib due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Both inotuzumab and pazopanib have been associated with QT interval prolongation.
    Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with pazopanib may result in increased serum concentrations of both drugs. Pazopanib is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and a substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
    Isoflurane: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be avoided with pazopanib include halogenated anesthetics.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid administering pazopanib in patients who require chronic treatment with a strong CYP3A4 inducer, such as rifampin. The concomitant use of pazopanib, a substrate for CYP3A4 and P-glycoprotein (P-gp), and rifampin, a strong CYP3A4 inducer and a P-gp inducer, may result in decreased pazopanib concentrations.
    Isoniazid, INH; Rifampin: (Major) Avoid administering pazopanib in patients who require chronic treatment with a strong CYP3A4 inducer, such as rifampin. The concomitant use of pazopanib, a substrate for CYP3A4 and P-glycoprotein (P-gp), and rifampin, a strong CYP3A4 inducer and a P-gp inducer, may result in decreased pazopanib concentrations.
    Isradipine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and isradipine, a CYP3A4 substrate, may cause an increase in systemic concentrations of isradipine. Use caution when administering these drugs concomitantly.
    Itraconazole: (Major) Avoid pazopanib use during and for 2 weeks after discontinuation of itraconazole treatment due the potential for increased pazopanib exposure and QT prolongation. If coadministration is unavoidable, reduce the pazopanib dose to 400 mg PO once daily and closely monitor for QT prolongation. Both pazopanib and itraconazole are associated with QT prolongation; coadministration may increase this risk. Pazopanib is a CYP3A4 and breast cancer resistance protein (BCRP) substrate; itraconazole is a strong CYP3A4 and BCRP inhibitor. Concurrent use of another strong CYP3A4 inhibitor increased the Cmax and AUC of pazopanib by 1.5-fold and 1.7-fold, respectively.
    Ivabradine: (Moderate) Use caution during coadministration of ivabradine and pazopanib as increased concentrations of ivabradine are possible. Ivabradine is primarily metabolized by CYP3A4; pazopanib is a weak inhibitor of CYP3A. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib with pazopanib due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Pazopanib has been reported to prolong the QT interval.
    Ixabepilone: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and ixabepilone, a CYP3A4 substrate, may cause an increase in systemic concentrations of ixabepilone. Use caution when administering these drugs concomitantly.
    Ketoconazole: (Major) Avoid concurrent administration of ketoconazole and pazopanib. If coadministration is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. Both pazopanib and ketoconazole are associated with QT prolongation; coadministration may increase this risk. In addition, coadministration of ketoconazole (a potent CYP3A4 inhibitor) with pazopanib (a CYP3A4 substrate) results in elevated pazopanib plasma concentrations and may increase the risk for adverse events, including QT prolongation. Following multiple doses of pazopanib 400 mg PO with multiple doses of ketoconazole 400 mg PO, the pazopanib AUC and Cmax values were increased by 1.7-fold and 1.5-fold, respectively, compared with pazopanib administered alone. Additionally, the administration of pazopanib eye drops with ketoconazole resulted in a 2-fold and 1.5-fold increase in pazopanib mean AUC and Cmax values, respectively, in healthy volunteers.
    Lansoprazole: (Major) Pazopanib displays pH-dependent solubility with decreased solubility at a higher pH. The concomitant use of pazopanib and proton pump inhibitors (PPIs) that elevate the gastric pH may reduce the bioavailability of pazopanib. In a study of patients with solid tumors, the AUC and Cmax of pazopanib were decreased by approximately 40% when coadministered with esomeprazole. If a drug is needed to raise the gastric pH, consider use of a short-acting antacid; separate antacid and pazopanib dosing by several hours.
    Lansoprazole; Amoxicillin; Clarithromycin: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and clarithromycin have been reported to prolong the QT interval. If pazopanib and clarithromycin must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a substrate for CYP3A4 and P-glycoprotein (P-gp) and weak inhibitor of CYP3A4. Clarithromycin is a strong inhibitor of CYP3A4, an inhibitor of P-gp, and substrate of CYP3A4. Concurrent administration of clarithromycin and pazopanib may result in increased pazopanib and/or clarithromycin concentrations; avoid use of these agents together if possible. If co-administration of pazopanib and clarithromycin is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. (Major) Pazopanib displays pH-dependent solubility with decreased solubility at a higher pH. The concomitant use of pazopanib and proton pump inhibitors (PPIs) that elevate the gastric pH may reduce the bioavailability of pazopanib. In a study of patients with solid tumors, the AUC and Cmax of pazopanib were decreased by approximately 40% when coadministered with esomeprazole. If a drug is needed to raise the gastric pH, consider use of a short-acting antacid; separate antacid and pazopanib dosing by several hours.
    Lansoprazole; Naproxen: (Major) Pazopanib displays pH-dependent solubility with decreased solubility at a higher pH. The concomitant use of pazopanib and proton pump inhibitors (PPIs) that elevate the gastric pH may reduce the bioavailability of pazopanib. In a study of patients with solid tumors, the AUC and Cmax of pazopanib were decreased by approximately 40% when coadministered with esomeprazole. If a drug is needed to raise the gastric pH, consider use of a short-acting antacid; separate antacid and pazopanib dosing by several hours.
    Lapatinib: (Major) Coadministration of pazopanib lapatinib is not advised due to the risk of QT prolongation; exposure to pazopanib may also increase. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct electrolyte abnormalities prior to treatment. Pazopanib is a P-glycoprotein (P-gp) substrate that has been reported to prolong the QT interval. Lapatinib is a P-gp inhibitor that has also been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib.
    Ledipasvir; Sofosbuvir: (Moderate) Caution and close monitoring of adverse reactions is advised with concomitant administration of pazopanib and ledipasvir; sofosbuvir. Both ledipasvir and pazopanib are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp) ; sofosbuvir is a P-gp substrate. In addition pazopanib and sofosbuvir are substrates of and breast cancer resistance protein (BCRP); ledipasvir is an inhibitor and substrate of BCRP. Taking these drugs together may increase plasma concentrations of all three drugs. According to the manufacturer, no dosage adjustments are required when ledipasvir; sofosbuvir is administered concurrently with P-gp inhibitors.
    Lefamulin: (Major) Avoid coadministration of lefamulin with pazopanib as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Pazopanib has been reported to prolong the QT interval.
    Lemborexant: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with pazopanib as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; pazopanib is a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
    Lenvatinib: (Major) Avoid coadministration of lenvatinib with pazopanib due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Pazopanib has also been reported to prolong the QT interval.
    Letermovir: (Moderate) An increase in the plasma concentration of pazopanib may occur if given with letermovir. Avoid coadministration in patients also receiving cyclosporine, because the magnitude of this interaction may be increased. If coadministration of pazopanib with both letermovir and cyclosporine cannot be avoided, reduce the pazopanib dose to 400 mg. Pazopanib is primarily metabolized by CYP3A4. 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. Concurrent administration with a strong CYP3A4 inhibitor increased the exposure (AUC) and maximum plasma concentration of pazopanib by up to 2- and 1.5-fold, respectively.
    Leuprolide: (Major) Coadministration of pazopanib and leuprolide is not advised due to the risk of QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT interval prolongation. Pazopanib has been reported to prolong the QT interval. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Leuprolide; Norethindrone: (Major) Coadministration of pazopanib and leuprolide is not advised due to the risk of QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT interval prolongation. Pazopanib has been reported to prolong the QT interval. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Levamlodipine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and amlodipine, a CYP3A4 substrate, may cause an increase in systemic concentrations of amlodipine. Use caution when administering these drugs concomitantly.
    Levofloxacin: (Major) Concurrent use of pazopanib and levofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be continued, closely monitor the patient for QT interval prolongation. Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Additionally, rare cases of TdP have been spontaneously reported during postmarketing surveillance in patients receiving levofloxacin. Pazopanib has also been reported to prolong the QT interval.
    Levoketoconazole: (Major) Avoid concurrent administration of ketoconazole and pazopanib. If coadministration is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. Both pazopanib and ketoconazole are associated with QT prolongation; coadministration may increase this risk. In addition, coadministration of ketoconazole (a potent CYP3A4 inhibitor) with pazopanib (a CYP3A4 substrate) results in elevated pazopanib plasma concentrations and may increase the risk for adverse events, including QT prolongation. Following multiple doses of pazopanib 400 mg PO with multiple doses of ketoconazole 400 mg PO, the pazopanib AUC and Cmax values were increased by 1.7-fold and 1.5-fold, respectively, compared with pazopanib administered alone. Additionally, the administration of pazopanib eye drops with ketoconazole resulted in a 2-fold and 1.5-fold increase in pazopanib mean AUC and Cmax values, respectively, in healthy volunteers.
    Levomethadyl: (Contraindicated) Levomethadyl has been established to have a causal association with QT prolongation and torsade de pointe. Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation.
    Levonorgestrel; Ethinyl Estradiol: (Moderate) Pazopanib is a substrate for CYP3A4. Ethinyl estradiol is an inhibitor of CYP3A4. Concurrent administration may result in increased pazopanib concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and ethinyl estradiol is required.
    Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Pazopanib is a substrate for CYP3A4. Ethinyl estradiol is an inhibitor of CYP3A4. Concurrent administration may result in increased pazopanib concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and ethinyl estradiol is required.
    Lidocaine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and lidocaine, a CYP3A4 substrate, may cause an increase in systemic concentrations of lidocaine. Use caution when administering these drugs concomitantly.
    Lidocaine; Epinephrine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and lidocaine, a CYP3A4 substrate, may cause an increase in systemic concentrations of lidocaine. Use caution when administering these drugs concomitantly.
    Lidocaine; Prilocaine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and lidocaine, a CYP3A4 substrate, may cause an increase in systemic concentrations of lidocaine. Use caution when administering these drugs concomitantly.
    Lithium: (Major) Lithium should be avoided with pazopanib. Lithium has been associated with QT prolongation. Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation.
    Lofexidine: (Major) Coadministration of lofexidine and pazopanib is not recommended due to the risk of additive QT prolongation and torsade de pointes (TdP). Monitor the ECG for QT prolongation if coadministration is required. Lofexidine may prolong the QT interval, and TdP has been reported during postmarketing use. Pazopanib is associated with QT interval prolongation.
    Lomitapide: (Major) Concomitant use of lomitapide and pazopanib may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Pazopanib is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
    Lonafarnib: (Major) Avoid coadministration of lonafarnib and pazopanib; concurrent use may increase the exposure of both drugs and the risk of adverse effects. If concomitant use is necessary, reduce to or continue lonafarnib at a dosage of 115 mg/m2 and reduce the pazopanib dose to 400 mg PO once daily. Additional pazopanib dosage adjustments may be necessary. Lonafarnib is a sensitive CYP3A4 substrate and P-gp and strong CYP3A4 inhibitor; pazopanib is a CYP3A4 and P-gp substrate and weak CYP3A4 inhibitor. Another strong CYP3A4 inhibitor increased the Cmax and AUC of pazopanib by 1.5-fold and 1.7-fold, respectively.
    Loperamide: (Major) Loperamide should be avoided in combination with pazopanib. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and loperamide must be continued, closely monitor the patient for QT interval prolongation. In addition, if these drugs are used together, the plasma concentrations of loperamide may increase, further increasing the risk of toxicity. Loperamide is metabolized by CYP3A4, CYP2C8, and CYP2D6. Pazopanib is a weak inhibitor of CYP3A4, CYP2C8, and CYP2D6. Monitor for cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, TdP, cardiac arrest) and other loperamide-associated adverse reactions, such as CNS effects.
    Loperamide; Simethicone: (Major) Loperamide should be avoided in combination with pazopanib. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and loperamide must be continued, closely monitor the patient for QT interval prolongation. In addition, if these drugs are used together, the plasma concentrations of loperamide may increase, further increasing the risk of toxicity. Loperamide is metabolized by CYP3A4, CYP2C8, and CYP2D6. Pazopanib is a weak inhibitor of CYP3A4, CYP2C8, and CYP2D6. Monitor for cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, TdP, cardiac arrest) and other loperamide-associated adverse reactions, such as CNS effects.
    Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with pazopanib due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Both drugs have been associated with QT prolongation. (Major) Avoid coadministration of pazopanib and ritonavir due to the potential for increased pazopanib exposure. If concurrent use is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. Pazopanib is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. Concurrent use of another strong CYP3A4 inhibitor increased the Cmax and AUC of pazopanib by 1.5-fold and 1.7-fold, respectively.
    Losartan: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and losartan, a CYP3A4 substrate, may cause an increase in systemic concentrations of losartan. Use caution when administering these drugs concomitantly.
    Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and losartan, a CYP3A4 substrate, may cause an increase in systemic concentrations of losartan. Use caution when administering these drugs concomitantly.
    Lovastatin: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and lovastatin, a CYP3A4 substrate, may cause an increase in systemic concentrations of lovastatin. Use caution when administering these drugs concomitantly.
    Lovastatin; Niacin: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and lovastatin, a CYP3A4 substrate, may cause an increase in systemic concentrations of lovastatin. Use caution when administering these drugs concomitantly.
    Lumacaftor; Ivacaftor: (Major) Avoid administering pazopanib in patients who require chronic treatment with a strong CYP3A4 inducer, such as lumacaftor; ivacaftor. Concomitant use may result in decreased pazopanib concentrations. Pazopanib is primarily metabolized by CYP3A4 and is also a substrate of CYP2C8 and the drug transporter P-glycoprotein (P-gp). Lumacaftor is a strong CYP3A inducer; in vitro data also suggest that lumacaftor; ivacaftor may induce and/or inhibit CYP2C8 and P-gp.
    Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as pazopanib. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Pazopanib has been reported to prolong the QT interval.
    Maprotiline: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be avoided with pazopanib include maprotiline.
    Maraviroc: (Minor) Use caution if coadministration of maraviroc with pazopanib is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and pazopanib is a weak CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Maribavir: (Major) Avoid coadministration of pazopanib and maribavir due to the potential for increased pazopanib exposure. Pazopanib is a P-gp and BCRP substrate; maribavir is a P-gp and BCRP inhibitor. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit P-gp or BCRP.
    Mefloquine: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering pazopanib with mefloquine. There is evidence that the use of halofantrine after mefloquine causes significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval, such as pazopanib. In addition, mefloquine is metabolized by CYP3A4 and is a P-gp inhibitor. Pazopanib inhibits CYP3A4 and is a substrate for P-gp. Concurrent use may increase the serum concentrations of mefloquine and/or pazopanib, further increasing the risk for QT prolongation.
    Meloxicam: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and meloxicam, a CYP3A4 substrate, may cause an increase in systemic concentrations of meloxicam. Use caution when administering these drugs concomitantly.
    Meperidine; Promethazine: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as promethazine, is not advised; pazopanib and promethazine have been reported to prolong the QT interval. If pazopanib and promethazine must be continued, closely monitor the patient for QT interval prolongation.
    Mesoridazine: (Contraindicated) Mesoridazine has been established to have a causal association with QT prolongation and torsade de pointe. Coadministration of pazopanib and other drugs that prolongs the QT interval is not advised; pazopanib has been reported to prolongs the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation.
    Metformin; Repaglinide: (Moderate) Pazopanib is a weak inhibitor of CYP3A4 and CYP2C8. Coadministration of pazopanib and repaglinide, a CYP3A4 and CYP2C8 substrate, may cause an increase in systemic concentrations of repaglinide. Use caution when administering these drugs concomitantly.
    Metformin; Rosiglitazone: (Moderate) Pazopanib is a weak inhibitor of CYP2C8. Coadministration of pazopanib and rosiglitazone, a CYP2C8 substrate, may cause an increase in systemic concentrations of rosiglitazone. Use caution when administering these drugs concomitantly.
    Methadone: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. At high doses, methadone is considered to be associated with an increased risk for QT prolongation and torsades de pointes (TdP). If pazopanib and methadone must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4 and CYP2D6. Coadministration of pazopanib and methadone, a CYP3A4 and CYP2D6 substrate, may cause an increase in systemic concentrations of methadone. Use caution when concurrent administration of pazopanib and methadone is necessary.
    Methylprednisolone: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and methylprednisolone, a CYP3A4 substrate, may cause an increase in systemic concentrations of methylprednisolone. Use caution when administering these drugs concomitantly. In addition, concomitant administration may predispose the patient to over-immunosuppression resulting in an increased risk for the development of severe infections.
    Metronidazole: (Major) Concomitant use of metronidazole and pazopanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Midazolam: (Moderate) Pazopanib resulted in an approximately 30% increase in mean AUC and Cmax of midazolam, a CYP3A4 substrate, when given concomitantly.
    Midostaurin: (Major) Avoid coadministration of pazopanib and midostaurin due to the potential for increased pazopanib exposure. Pazopanib is a BCRP substrate; midostaurin is a BCRP inhibitor. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit BCRP. Concomitant use of midostaurin and pazopanib also increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Mifepristone: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as mifepristone, is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Although specific drug interactions with mifepristone have not been studied, the use of mifepristone with CYP3A inhibitors may result in increased mifepristone concentrations and an increased risk of QT prolongation.
    Mirtazapine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and pazopanib. Coadministration of pazopanib and other drugs that prolong the QT interval is not advised. If pazopanib and mirtazapine must be coadministered, closely monitor for QT prolongation. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine, primarily following overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation.
    Mitapivat: (Major) Avoid coadministration of pazopanib and mitapivat due to the potential for increased pazopanib exposure. Pazopanib is a P-gp substrate; mitapivat is a P-gp inhibitor. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit P-gp.
    Mitotane: (Major) Avoid the concomitant use of mitotane with pazopanib due to decreased exposure and possible decreased efficacy. Mitotane is a strong CYP3A4 inducer and pazopanib is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of pazopanib.
    Mobocertinib: (Major) Concomitant use of mobocertinib and pazopanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Modafinil: (Moderate) Pazopanib is a substrate for and a weak inhibitor of CYP3A4. Coadministration of pazopanib and modafinil, a CYP3A4 substrate, may cause an increase in systemic concentrations of modafinil. In addition, modafinil is an inducer of CYP3A4 and may cause a decrease in systemic concentrations of pazopanib. Use caution when administering these drugs concomitantly.
    Moxifloxacin: (Major) Concurrent use of pazopanib and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be continued, closely monitor the patient for QT interval prolongation. Pazopanib has been reported to prolong the QT interval. Moxifloxacin has also been associated with prolongation of the QT interval. Additionally, post-marketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded.
    Nafcillin: (Moderate) Pazopanib is a substrate for CYP3A4. Plasma pazopanib concentrations may be decreased by concurrent administration with a CYP3A4 inducer such as nafcillin. Use caution if chronic use of CYP3A4 inducers and pazopanib can not be avoided.
    Nanoparticle Albumin-Bound Sirolimus: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 if coadministration with pazopanib is necessary. The dose of sirolimus may also need to be reduced with coadministration of pazopanib. Monitor sirolimus serum concentrations as appropriate and watch for sirolimus-related adverse reactions with coadministration of pazopanib. Sirolimus is a sensitive CYP3A substrate with a narrow therapeutic range; pazopanib is a weak CYP3A inhibitor.
    Naproxen; Esomeprazole: (Major) Pazopanib displays pH-dependent solubility with decreased solubility at a higher pH. The concomitant use of pazopanib and proton pump inhibitors (PPIs) that elevate the gastric pH may reduce the bioavailability of pazopanib. In a study of patients with solid tumors, the AUC and Cmax of pazopanib were decreased by approximately 40% when coadministered with esomeprazole. If a drug is needed to raise the gastric pH, consider use of a short-acting antacid; separate antacid and pazopanib dosing by several hours.
    Nebivolol: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with pazopanib. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as pazopanib, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible.
    Nebivolol; Valsartan: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with pazopanib. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as pazopanib, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible.
    Nefazodone: (Major) Avoid administering pazopanib with strong CYP3A4 inhibitors, such as nefazodone. If co-administration with a strong CYP3A4 inhibitor is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. The concomitant use of pazopanib, a weak CYP3A4 inhibitor and a CYP3A4 substrate, and nefazodone, a strong CYP3A4 inhibitor and CYP3A4 substrate, may result in increased pazopanib and/or nefazodone concentrations.
    Nelfinavir: (Major) Avoid administering pazopanib with strong CYP3A4 inhibitors, such as nelfinavir. If co-administration with a strong CYP3A4 inhibitor is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. The concomitant use of pazopanib, a weak CYP3A4 inhibitor and a CYP3A4 and P-glycoprotein (P-gp) substrate, and nelfinavir, a CYP3A4 and P-gp inhibitor and a CYP3A4 and P-gp substrate, may result in altered pazopanib and/or nelfinavir concentrations.
    Neratinib: (Major) Avoid coadministration of pazopanib and neratinib due to the potential for increased pazopanib exposure. Pazopanib is a P-gp substrate; neratinib is a P-gp inhibitor. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit P-gp.
    Nevirapine: (Moderate) Pazopanib is a substrate for and a weak inhibitor of CYP3A4. Coadministration of pazopanib and nevirapine, a CYP3A4 substrate, may cause an increase in systemic concentrations of nevirapine. In addition, nevirapine is an inducer of CYP3A4 and may cause a decrease in systemic concentrations of pazopanib. Use caution when administering these drugs concomitantly.
    Niacin; Simvastatin: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and simvastatin, a CYP3A4 substrate, may cause an increase in systemic concentrations of simvastatin. Use caution when administering these drugs concomitantly.
    Nilotinib: (Major) Avoid the concomitant use of nilotinib with pazopanib due to an increased risk for QT prolongation. Pazopanib has been reported to prolong the QT interval. Sudden death and QT interval prolongation have occurred in patients who received nilotinib therapy.
    Nimodipine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and nimodipine, a CYP3A4 substrate, may cause an increase in systemic concentrations of nimodipine. Use caution when administering these drugs concomitantly.
    Nirmatrelvir; Ritonavir: (Major) Avoid coadministration of pazopanib and ritonavir due to the potential for increased pazopanib exposure. If concurrent use is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. Pazopanib is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. Concurrent use of another strong CYP3A4 inhibitor increased the Cmax and AUC of pazopanib by 1.5-fold and 1.7-fold, respectively.
    Nisoldipine: (Major) Avoid coadministration of nisoldipine with pazopanib due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A4 substrate and pazopanib is a weak CYP3A4 inhibitor.
    Nizatidine: (Major) Avoid coadministration of pazopanib with H2-blockers due to decreased absorption of pazopanib, which may decrease efficacy. If concomitant administration with a gastric acid-reducing agent is unavoidable, consider the use of a short-acting antacid in place of an H2-blocker; separate administration of the short-acting antacid and pazopanib by several hours to avoid a reduction in pazopanib exposure. Concomitant use of pazopanib with a proton pump inhibitor decreased pazopanib exposure (AUC and Cmax) by approximately 40%.
    Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Pazopanib is a substrate for CYP3A4. Ethinyl estradiol is an inhibitor of CYP3A4. Concurrent administration may result in increased pazopanib concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and ethinyl estradiol is required.
    Norethindrone; Ethinyl Estradiol: (Moderate) Pazopanib is a substrate for CYP3A4. Ethinyl estradiol is an inhibitor of CYP3A4. Concurrent administration may result in increased pazopanib concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and ethinyl estradiol is required.
    Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Pazopanib is a substrate for CYP3A4. Ethinyl estradiol is an inhibitor of CYP3A4. Concurrent administration may result in increased pazopanib concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and ethinyl estradiol is required.
    Norfloxacin: (Major) Concurrent use of pazopanib and norfloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be continued, closely monitor the patient for QT interval prolongation. Pazopanib has been reported to prolong the QT interval. Quinolones have also been associated with QT prolongation and TdP. For norfloxacin specifically, extremely rare cases of TdP were reported during post-marketing surveillance. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Norgestimate; Ethinyl Estradiol: (Moderate) Pazopanib is a substrate for CYP3A4. Ethinyl estradiol is an inhibitor of CYP3A4. Concurrent administration may result in increased pazopanib concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and ethinyl estradiol is required.
    Nortriptyline: (Minor) Coadministration of pazopanib and other drugs that prolong the QT interval, such as tricyclic antidepressants is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Amitriptyline, clomipramine and imipramine are CYP3A4 substrates. Coadministration of pazopanib may cause an increase in systemic concentrations of the tricyclic antidepressant. Use caution when administering these drugs concomitantly.
    Octreotide: (Major) Concurrent use of pazopanib and octreotide is not advised. Closely monitor the patient for QT interval prolongation if coadministration of pazopanib and octreotide cannot be avoided. Pazopanib has been reported to prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of torsade de pointes (TdP), the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Ofloxacin: (Major) Concurrent use of pazopanib and ofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be coadministered, closely monitor the patient for QT interval prolongation. Pazopanib has been reported to prolong the QT interval. Some quinolones, including ofloxacin, have also been associated with QT prolongation. Additionally, post-marketing surveillance for ofloxacin has identified very rare cases of TdP.
    Olanzapine: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be avoided with pazopanib include olanzapine.
    Olanzapine; Fluoxetine: (Major) Coadministration of fluoxetine and pazopanib is not recommended due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Pazopanib is associated with QT interval prolongation. QT prolongation and TdP have been reported in patients treated with fluoxetine. (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be avoided with pazopanib include olanzapine.
    Olanzapine; Samidorphan: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be avoided with pazopanib include olanzapine.
    Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and amlodipine, a CYP3A4 substrate, may cause an increase in systemic concentrations of amlodipine. Use caution when administering these drugs concomitantly.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid coadministration of pazopanib and ritonavir due to the potential for increased pazopanib exposure. If concurrent use is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. Pazopanib is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. Concurrent use of another strong CYP3A4 inhibitor increased the Cmax and AUC of pazopanib by 1.5-fold and 1.7-fold, respectively. (Major) Avoid concurrent administration of pazopanib with dasabuvir; ombitasvir; paritaprevir; ritonavir if possibile. Complex metabolic interactions may occur resulting in elevated plasma concentrations of all 5 drugs. If coadministration is unavoidable, reduce the pazopanib dosage to 400 mg PO once daily, and monitor for adverse effects. Further dosage adjustments may be necessary depending on tolerability. Both pazopanib and ritonavir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. Paritaprevir and dasabuvir (minor) are also CYP3A4 substrates. Pazopanib inhibits CYP2D6 and CYP2C8; dasabuvir is primarily metabolized by CYP2C8 and CYP2D6 is partially responsible for the metabolism of ritonavir. Pazopanib is a substrate for the breast cancer resistance protein (BCRP); ritonavir, dasabuvir, paritaprevir are BCRP inhibitors. Finally, pazopanib is a substrate and inhibitor of the drug transporter P-glycoprotein (P-gp); dasabuvir, ombitasvir, paritaprevir and ritonavir are all substrates of P-gp. Ritonavir is also a P-gp inhibitor.
    Omeprazole: (Major) Pazopanib displays pH-dependent solubility with decreased solubility at a higher pH. The concomitant use of pazopanib and proton pump inhibitors (PPIs) that elevate the gastric pH may reduce the bioavailability of pazopanib. In a study of patients with solid tumors, the AUC and Cmax of pazopanib were decreased by approximately 40% when coadministered with esomeprazole. If a drug is needed to raise the gastric pH, consider use of a short-acting antacid; separate antacid and pazopanib dosing by several hours.
    Omeprazole; Amoxicillin; Rifabutin: (Major) Pazopanib displays pH-dependent solubility with decreased solubility at a higher pH. The concomitant use of pazopanib and proton pump inhibitors (PPIs) that elevate the gastric pH may reduce the bioavailability of pazopanib. In a study of patients with solid tumors, the AUC and Cmax of pazopanib were decreased by approximately 40% when coadministered with esomeprazole. If a drug is needed to raise the gastric pH, consider use of a short-acting antacid; separate antacid and pazopanib dosing by several hours.
    Omeprazole; Sodium Bicarbonate: (Major) Pazopanib displays pH-dependent solubility with decreased solubility at a higher pH. The concomitant use of pazopanib and proton pump inhibitors (PPIs) that elevate the gastric pH may reduce the bioavailability of pazopanib. In a study of patients with solid tumors, the AUC and Cmax of pazopanib were decreased by approximately 40% when coadministered with esomeprazole. If a drug is needed to raise the gastric pH, consider use of a short-acting antacid; separate antacid and pazopanib dosing by several hours. (Moderate) Separate administration of pazopanib and antacids by several hours if coadministration is necessary in order to avoid a reduction in pazopanib exposure, which may decrease efficacy.
    Ondansetron: (Major) Coadministration of pazopanib and ondansetron is not advised. If coadministration is unavoidable, monitor ECG for evidence of QT prolongation. Pazopanib has been reported to prolong the QT interval. Ondansetron has been associated with a dose-related increase in the QT interval and postmarketing reports of torsade de pointes (TdP).
    Osilodrostat: (Major) Coadministration of osilodrostat and pazopanib is not recommended due to the risk of additive QT prolongation. Monitor the ECG for QT prolongation if coadministration is required. Pazopanib is associated with QT interval prolongation. Osilodrostat is associated with dose-dependent QT prolongation.
    Osimertinib: (Major) According to the manufacturer of pazopanib, coadministration with other medications that prolong the QT interval, such as osimertinib, is not advised. If concomitant use is unavoidable, monitor electrolytes and ECGs for QT prolongation; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Additionally, monitor for an increase in pazopanib related adverse reactions if coadministration with osimertinib is necessary. Pazopanib is a BCRP and P-glycoprotein (P-gp) substrate that has been reported to prolong the QT interval. Osimertinib is a BCRP and P-gp inhibitor that is associated with concentration-dependent QT prolongation.
    Oxaliplatin: (Major) Concomitant use of pazopanib with oxaliplatin is not advised due to the risk of QT prolongation. If coadministration is unavoidable, closely monitor electrolytes and ECGs for QT prolongation; correct electrolyte abnormalities prior to administration of oxaliplatin. Pazopanib has been associated with QT prolongation; QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Oxcarbazepine: (Moderate) Pazopanib is a substrate for CYP3A4. Plasma pazopanib concentrations may be decreased by concurrent administration with a CYP3A4 inducer such as oxcarbazepine. Use caution if chronic use of CYP3A4 inducers and pazopanib can not be avoided.
    Oxybutynin: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and oxybutynin a CYP3A4 substrate, may cause an increase in systemic concentrations of oxybutynin. Use caution when administering these drugs concomitantly.
    Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. If pazopanib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a weak inhibitor like pazopanib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If pazopanib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
    Ozanimod: (Major) In general, do not initiate ozanimod in patients taking pazopanib due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If concomitant use is necessary, closely monitor the patient for QT interval prolongation. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Pazopanib has been reported to prolong the QT interval.
    Paclitaxel: (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.
    Pacritinib: (Major) Avoid coadministration of pazopanib and pacritinib due to the potential for increased pazopanib exposure. Concomitant use may also increase the risk of QT/QTc prolongation and torsade de pointes (TdP). Pazopanib is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit P-gp.
    Panobinostat: (Major) The co-administration of panobinostat with pazopanib is not recommended; QT prolongation has been reported with both agents. Pazopanib is a CYP3A4 inhibitor and panobinostat is a CYP3A4 substrate. The panobinostat Cmax and AUC (0-48hr) values were increased by 62% and 73%, respectively, in patients with advanced cancer who received a single 20 mg-dose of panobinostat after taking 14 days of a strong CYP3A4 inhibitor. Although an initial panobinostat dose reduction is recommended in patients taking concomitant strong CYP3A4 inhibitors, no dose recommendations with mild or moderate CYP3A4 inhibitors are provided by the manufacturer. If concomitant use of pazopanib and panobinostat cannot be avoided, closely monitor electrocardiograms and for signs and symptoms of panobinostat toxicity such as cardiac arrhythmias, diarrhea, bleeding, infection, and hepatotoxicity. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve.
    Pantoprazole: (Major) Pazopanib displays pH-dependent solubility with decreased solubility at a higher pH. The concomitant use of pazopanib and proton pump inhibitors (PPIs) that elevate the gastric pH may reduce the bioavailability of pazopanib. In a study of patients with solid tumors, the AUC and Cmax of pazopanib were decreased by approximately 40% when coadministered with esomeprazole. If a drug is needed to raise the gastric pH, consider use of a short-acting antacid; separate antacid and pazopanib dosing by several hours.
    Paricalcitol: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and paricalcitol, a CYP3A4 substrate, may cause an increase in systemic concentrations of paricalcitol. Use caution when administering these drugs concomitantly.
    Pasireotide: (Major) Coadministration of pazopanib and pasireotide is not advised, as coadministration may have additive effects on the prolongation of the QT interval. If pazopanib and pasireotide must be continued, closely monitor the patient for QT interval prolongation.
    Pentamidine: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be avoided with pazopanib include pentamidine.
    Perindopril; Amlodipine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and amlodipine, a CYP3A4 substrate, may cause an increase in systemic concentrations of amlodipine. Use caution when administering these drugs concomitantly.
    Perphenazine: (Minor) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be avoided with pazopanib include perphenazine.
    Perphenazine; Amitriptyline: (Minor) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be avoided with pazopanib include perphenazine. (Minor) Coadministration of pazopanib and other drugs that prolong the QT interval, such as tricyclic antidepressants is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Amitriptyline, clomipramine and imipramine are CYP3A4 substrates. Coadministration of pazopanib may cause an increase in systemic concentrations of the tricyclic antidepressant. Use caution when administering these drugs concomitantly.
    Phenobarbital: (Major) Avoid administering pazopanib in patients who require chronic treatment with a strong CYP3A4 inducer, such as phenobarbital. The concomitant use of pazopanib, a CYP3A4 substrate, and phenobarbital, a strong CYP3A4 inducer, may result in decreased pazopanib concentrations.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid administering pazopanib in patients who require chronic treatment with a strong CYP3A4 inducer, such as phenobarbital. The concomitant use of pazopanib, a CYP3A4 substrate, and phenobarbital, a strong CYP3A4 inducer, may result in decreased pazopanib concentrations.
    Phentermine; Topiramate: (Moderate) Coadministration of pazopanib and topiramate may cause a decrease in systemic concentrations of pazopanib. Use caution when administering these drugs concomitantly. Pazopanib is a substrate for CYP3A4. Topiramate in a weak CYP3A4 inducer.
    Phenytoin: (Moderate) Pazopanib is a substrate for CYP3A4. Plasma pazopanib concentrations may be decreased by concurrent administration with a CYP3A4 inducer such as phenytoin. Use caution if chronic use of CYP3A4 inducers and pazopanib can not be avoided.
    Pimavanserin: (Major) Co-administration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and pimavanserin have been reported to prolong the QT interval. If pazopanib and pimavanserin must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4 and pimavanserin is a substrate for CYP3A4. Concurrent administration of pimavanserin and pazopanib may result in increased pazopanib and/or pimavanserin concentrations. Use caution when concurrent administration is necessary.
    Pimozide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of pazopanib with pimozide is contraindicated.
    Pitolisant: (Major) Avoid coadministration of pitolisant with pazopanib as concurrent use may increase the risk of QT prolongation. If coadministration is necessary, closely monitor the patient for QT interval prolongation. Pitolisant prolongs the QT interval. Pazopanib has also been reported to prolong the QT interval
    Ponesimod: (Major) Avoid coadministration of pazopanib and ponesimod due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP); additive immunosuppression may also occur which may extend the duration or severity of immune suppression. If concomitant use is unavoidable, monitor ECGs, electrolytes, and for signs and symptoms of infection; correct hypokalemia, hypomagnesemia, and hypocalcemia. Pazopanib has been associated with QT prolongation. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
    Posaconazole: (Contraindicated) Concurrent use of pazopanib and posaconazole is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Pazopanib is a substrate for CYP3A4 and P-glycoprotein (P-gp). Posaconazole is an inhibitor of CYP3A4 and P-gp. Concurrent administration of posaconazole and pazopanib may result in increased pazopanib concentrations, causing an increased risk for adverse events, such as QT prolongation.
    Prednisolone: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and prednisolone, a CYP3A4 substrate, may cause an increase in systemic concentrations of prednisolone. Use caution when administering these drugs concomitantly. In addition, concomitant administration may predispose the patient to over-immunosuppression resulting in an increased risk for the development of severe infections.
    Prednisone: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and prednisone, a CYP3A4 substrate, may cause an increase in systemic concentrations of prednisone. Use caution when administering these drugs concomitantly. In addition, concomitant administration may predispose the patient to over-immunosuppression resulting in an increased risk for the development of severe infections.
    Primaquine: (Major) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include pazopanib.
    Probenecid; Colchicine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and colchicine, a CYP3A4 substrate, may cause an increase in systemic concentrations of colchicine. Use caution when administering these drugs concomitantly.
    Procainamide: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be avoided with pazopanib include procainamide.
    Prochlorperazine: (Minor) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be avoided with pazopanib include prochlorperazine.
    Promethazine: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as promethazine, is not advised; pazopanib and promethazine have been reported to prolong the QT interval. If pazopanib and promethazine must be continued, closely monitor the patient for QT interval prolongation.
    Promethazine; Dextromethorphan: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as promethazine, is not advised; pazopanib and promethazine have been reported to prolong the QT interval. If pazopanib and promethazine must be continued, closely monitor the patient for QT interval prolongation. (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Promethazine; Phenylephrine: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as promethazine, is not advised; pazopanib and promethazine have been reported to prolong the QT interval. If pazopanib and promethazine must be continued, closely monitor the patient for QT interval prolongation.
    Propafenone: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and propafenone have been reported to prolong the QT interval. If pazopanib and propafenone must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4 and a substrate for P-glycoprotein (P-gp). Propafenone is a substrate for CYP3A4 and an inhibitor of P-gp. Concurrent administration of propafenone and pazopanib may result in increased pazopanib concentrations and/or increased propafenone concentrations. Use caution when concurrent administration of propafenone and pazopanib is necessary.
    Proton pump inhibitors: (Major) Pazopanib displays pH-dependent solubility with decreased solubility at a higher pH. The concomitant use of pazopanib and proton pump inhibitors (PPIs) that elevate the gastric pH may reduce the bioavailability of pazopanib. In a study of patients with solid tumors, the AUC and Cmax of pazopanib were decreased by approximately 40% when coadministered with esomeprazole. If a drug is needed to raise the gastric pH, consider use of a short-acting antacid; separate antacid and pazopanib dosing by several hours.
    Protriptyline: (Minor) Coadministration of pazopanib and other drugs that prolong the QT interval, such as tricyclic antidepressants is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Amitriptyline, clomipramine and imipramine are CYP3A4 substrates. Coadministration of pazopanib may cause an increase in systemic concentrations of the tricyclic antidepressant. Use caution when administering these drugs concomitantly.
    Quazepam: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and quazepam, a CYP3A4 substrate, may cause an increase in systemic concentrations of quazepam. Use caution when administering these drugs concomitantly.
    Quetiapine: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. If pazopanib and quetiapine must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and quetiapine, a CYP3A4 substrate, may cause an increase in systemic concentrations of quetiapine. Use caution when concurrent administration is necessary.
    Quinidine: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and quinidine (including dextromethorphan; quinidine have been reported to prolong the QT interval. If pazopanib and quinidine must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4 and a substrate for P-glycoprotein (P-gp). Quinidine is a substrate for CYP3A4 and an inhibitor of P-gp. Concurrent administration of quinidine and pazopanib may result in increased pazopanib and/or quinidine concentrations. Use caution when concurrent administration is necessary.
    Quinine: (Major) Concurrent use of quinine and pazopanib should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Pazopanib has also been reported to prolong the QT interval. In addition, both drugs are CYP3A4 inhibitors and substrates; coadministration may increase serum concentrations of both drugs. Dose adjustment of pazopanib may be necessary when coadministration of pazopanib and quinine is required.
    Rabeprazole: (Major) Pazopanib displays pH-dependent solubility with decreased solubility at a higher pH. The concomitant use of pazopanib and proton pump inhibitors (PPIs) that elevate the gastric pH may reduce the bioavailability of pazopanib. In a study of patients with solid tumors, the AUC and Cmax of pazopanib were decreased by approximately 40% when coadministered with esomeprazole. If a drug is needed to raise the gastric pH, consider use of a short-acting antacid; separate antacid and pazopanib dosing by several hours.
    Ramelteon: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and ramelteon, a CYP3A4 substrate, may cause an increase in systemic concentrations of ramelteon. Use caution when administering these drugs concomitantly.
    Ranitidine: (Major) Avoid coadministration of pazopanib with H2-blockers due to decreased absorption of pazopanib, which may decrease efficacy. If concomitant administration with a gastric acid-reducing agent is unavoidable, consider the use of a short-acting antacid in place of an H2-blocker; separate administration of the short-acting antacid and pazopanib by several hours to avoid a reduction in pazopanib exposure. Concomitant use of pazopanib with a proton pump inhibitor decreased pazopanib exposure (AUC and Cmax) by approximately 40%.
    Ranolazine: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and ranolazine have been reported to prolong the QT interval. If pazopanib and ranolazine must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of and substrate for CYP3A4 and a substrate for P-glycoprotein (P-gp). Ranolazine is a substrate for and an inhibitor of CYP3A4 and P-gp. Concurrent administration of ranolazine and pazopanib may result in increased pazopanib concentrations and/or increased ranolazine concentrations. Dose reduction of pazopanib should be considered when coadministration of pazopanib and ranolazine is necessary.
    Regorafenib: (Major) Avoid coadministration of pazopanib and regorafenib due to the potential for increased pazopanib exposure. Pazopanib is a BCRP substrate; regorafenib is a BCRP inhibitor. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit BCRP.
    Relugolix: (Major) Avoid coadministration of relugolix with pazopanib due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia, hypomagnesemia, and hypocalcemia. Pazopanib has been associated with QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
    Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid coadministration of relugolix with pazopanib due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia, hypomagnesemia, and hypocalcemia. Pazopanib has been associated with QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
    Repaglinide: (Moderate) Pazopanib is a weak inhibitor of CYP3A4 and CYP2C8. Coadministration of pazopanib and repaglinide, a CYP3A4 and CYP2C8 substrate, may cause an increase in systemic concentrations of repaglinide. Use caution when administering these drugs concomitantly.
    Ribociclib: (Major) Avoid coadministration of ribociclib with pazopanib due to an increased risk for QT prolongation. Additionally, the systemic exposure of pazopanib may be increased resulting in an increase in treatment-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Pazopanib is a CYP3A4 substrate that has also been associated with QT prolongation. Concomitant use may increase the risk for QT prolongation.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with pazopanib due to an increased risk for QT prolongation. Additionally, the systemic exposure of pazopanib may be increased resulting in an increase in treatment-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Pazopanib is a CYP3A4 substrate that has also been associated with QT prolongation. Concomitant use may increase the risk for QT prolongation.
    Rifampin: (Major) Avoid administering pazopanib in patients who require chronic treatment with a strong CYP3A4 inducer, such as rifampin. The concomitant use of pazopanib, a substrate for CYP3A4 and P-glycoprotein (P-gp), and rifampin, a strong CYP3A4 inducer and a P-gp inducer, may result in decreased pazopanib concentrations.
    Rifapentine: (Major) Avoid coadministration of pazopanib with rifapentine due to the potential for decreased plasma concentrations of pazopanib. Pazopanib should not be used if chronic use of rifapentine cannot be avoided. Pazopanib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
    Rilpivirine: (Major) Concurrent use of pazopanib and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be continued, closely monitor the patient for QT interval prolongation. Pazopanib has been reported to prolong the QT interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and rilpivirine, a CYP3A4 substrate, may cause an increase in systemic concentrations of rilpivirine.
    Risperidone: (Major) Both risperidone and pazopanib have been associated with a possible risk for QT prolongation and torsade de pointes; therefore, caution is advisable during coadministration. If concurrent treatment is required and the patient has risk factors for cardiac disease or arrhythmias, close monitoring is recommended.
    Ritonavir: (Major) Avoid coadministration of pazopanib and ritonavir due to the potential for increased pazopanib exposure. If concurrent use is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. Pazopanib is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. Concurrent use of another strong CYP3A4 inhibitor increased the Cmax and AUC of pazopanib by 1.5-fold and 1.7-fold, respectively.
    Rolapitant: (Moderate) Use caution if pazopanib and rolapitant are used concurrently, and monitor for pazopanib-related adverse effects. Pazopanib is a substrate of the Breast Cancer Resistance Protein (BCRP) and P-glycoprotein (P-gp), where an increase in exposure may significantly increase adverse effects; rolapitant is a BCRP and P-gp inhibitor. The Cmax and AUC of another BCRP substrate, sulfasalazine, were increased by 140% and 130%, respectively, on day 1 with rolapitant, and by 17% and 32%, respectively, on day 8 after rolapitant administration. When rolapitant was administered with digoxin, a P-gp substrate, the day 1 Cmax and AUC were increased by 70% and 30%, respectively; the Cmax and AUC on day 8 were not studied. Additionally, pazopanib is also a weak inhibitor of CYP3A4 and rolapitant is a CYP3A4 substrate. Theoretically this could increase rolapitant concentrations, but this effect is not expected to be clinically relevant.
    Romidepsin: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and romidepsin have been reported to prolong the QT interval. If pazopanib and romidepsin must be continued, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and romidepsin, a CYP3A4 substrate, may cause an increase in systemic concentrations of romidepsin. Use caution when concurrent administration is necessary.
    Ropivacaine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and ropivacaine, a CYP3A4 substrate, may cause an increase in systemic concentrations of ropivacaine. Use caution when administering these drugs concomitantly.
    Rosiglitazone: (Moderate) Pazopanib is a weak inhibitor of CYP2C8. Coadministration of pazopanib and rosiglitazone, a CYP2C8 substrate, may cause an increase in systemic concentrations of rosiglitazone. Use caution when administering these drugs concomitantly.
    Saquinavir: (Contraindicated) Concurrent use of pazopanib and saquinavir boosted with ritonavir is contraindicated due to the risk of life threatening cardiac arrhythmias such as torsade de pointes (TdP). Pazopanib is a weak inhibitor of CYP3A4, which may lead to increased serum concentrations of saquinavir when given concomitantly, thus increasing the risk of drug toxicity and proarrhythmic effects. Pazopanib is also substrate for CYP3A4 and P-glycoprotein (P-gp). Saquinavir is a strong inhibitor of CYP3A4 and P-gp. Concurrent administration of saquinavir and pazopanib may also result in increased pazopanib concentrations. Additionally, saquinavir boosted with ritonavir causes dose-dependent QT and PR prolongation, which could further increase the risk for TdP if coadministered with pazopanib.
    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.
    Segesterone Acetate; Ethinyl Estradiol: (Moderate) Pazopanib is a substrate for CYP3A4. Ethinyl estradiol is an inhibitor of CYP3A4. Concurrent administration may result in increased pazopanib concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and ethinyl estradiol is required.
    Selpercatinib: (Major) Coadministration of selpercatinib and pazopanib is not recommended due to the potential for additive QT prolongation. Monitor ECGs more frequently for QT prolongation if coadministration is necessary. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Pazopanib has been reported to prolong the QT interval.
    Sertraline: (Major) Coadministration of pazopanib with sertraline is not recommended. If concomitant use is necessary, closely monitor the patient for QT interval prolongation. Pazopanib has been reported to prolong the QT interval. QTc prolongation and torsade de pointes (TdP) have been reported during postmarketing use of sertraline; most cases had confounding risk factors. The risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure).
    Sevoflurane: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be avoided with pazopanib include halogenated anesthetics.
    Sildenafil: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and sildenafil, a CYP3A4 substrate, may cause an increase in systemic concentrations of sildenafil. Use caution when administering these drugs concomitantly.
    Simeprevir: (Moderate) Concurrent administration of simeprevir, a CYP3A4 substrate, with pazopanib, a moderate CYP3A4 inhibitor, may increase simeprevir serum concentrations. In addition, the therapeutic effects of pazopanib, a substrate for CYP3A4, P-glycoprotein (P-gp), and the breast cancer resistant protein (BCRP), may be increased by simeprevir, a P-gp, BCRP, and a mild intestinal CYP3A4 inhibitor. If these drugs are administered together, monitor patients for adverse effects,.
    Simvastatin: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and simvastatin, a CYP3A4 substrate, may cause an increase in systemic concentrations of simvastatin. Use caution when administering these drugs concomitantly.
    Simvastatin; Sitagliptin: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and simvastatin, a CYP3A4 substrate, may cause an increase in systemic concentrations of simvastatin. Use caution when administering these drugs concomitantly.
    Siponimod: (Major) Avoid coadministration of siponimod and pazopanib due to the potential for additive QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Pazopanib has been reported to prolong the QT interval.
    Sirolimus: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 if coadministration with pazopanib is necessary. The dose of sirolimus may also need to be reduced with coadministration of pazopanib. Monitor sirolimus serum concentrations as appropriate and watch for sirolimus-related adverse reactions with coadministration of pazopanib. Sirolimus is a sensitive CYP3A substrate with a narrow therapeutic range; pazopanib is a weak CYP3A inhibitor.
    Sodium Bicarbonate: (Moderate) Separate administration of pazopanib and antacids by several hours if coadministration is necessary in order to avoid a reduction in pazopanib exposure, which may decrease efficacy.
    Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with pazopanib. Taking these medications together may increase the plasma concentrations of velpatasvir and pazopanib, potentially resulting in adverse events. Pazopanib is a substrate of the drug transporters P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP); velpatasvir is a P-gp and BCRP inhibitor. Pazopanib is also a weak inhibitor of the hepatic enzymes CYP3A4 and CYP2C8. Velpatasvir is a substrate of both enzymes.
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid concurrent administration of voxilaprevir with pazopanib. Taking these medications together may increase pazopanib plasma concentrations, potentially increasing the risk for adverse events. Pazopanib is a substrate for the drug transporters P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). Voxilaprevir is a P-gp and BCRP inhibitor. (Moderate) Use caution when administering velpatasvir with pazopanib. Taking these medications together may increase the plasma concentrations of velpatasvir and pazopanib, potentially resulting in adverse events. Pazopanib is a substrate of the drug transporters P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP); velpatasvir is a P-gp and BCRP inhibitor. Pazopanib is also a weak inhibitor of the hepatic enzymes CYP3A4 and CYP2C8. Velpatasvir is a substrate of both enzymes.
    Solifenacin: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and solifenacin, a CYP3A4 substrate, may cause an increase in systemic concentrations of solifenacin. Use caution when administering these drugs concomitantly.
    Sorafenib: (Major) Coadministration of pazopanib and sorafenib is not advised due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Pazopanib has been reported to prolong the QT interval. Sorafenib is also associated with QTc prolongation.
    Sotalol: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as sotalol, is not advised; pazopanib has been reported to prolong the QT interval. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. If pazopanib and sotalol must be continued, closely monitor the patient for QT interval prolongation.
    Sotorasib: (Major) Avoid coadministration of pazopanib and sotorasib due to the potential for increased pazopanib exposure. Pazopanib is a P-gp substrate; sotorasib is a P-gp inhibitor. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit P-gp.
    St. John's Wort, Hypericum perforatum: (Moderate) Pazopanib is a substrate for CYP3A4 and P-glycoprotein (Pgp). Plasma pazopanib concentrations may be decreased by concurrent administration with a CYP3A4 and Pgp inducer such as St. John's Wort, Hypericum perforatum. Use caution if chronic use of CYP3A4 and Pgp inducers and pazopanib can not be avoided.
    Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if pazopanib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of pazopanib is necessary. If pazopanib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like pazopanib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If pazopanib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
    Sunitinib: (Major) Coadministration of pazopanib with other drugs that prolong the QT interval, such as sunitinib, is not advised. If concomitant use is unavoidable, closely monitor the patient for QT interval prolongation. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Pazopanib has also been reported to prolong the QT interval.
    Tacrolimus: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and tacrolimus have been reported to prolong the QT interval. If pazopanib and tacrolimus must be continued, closely monitor the patient for QT interval prolongation. Also, reducing the tacrolimus dose, close monitoring of tacrolimus whole blood concentrations, and monitoring for QT prolongation is recommended. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and tacrolimus, a CYP3A4 substrate, may cause an increase in systemic concentrations of tacrolimus. Use caution when concurrent administration is necessary.
    Tadalafil: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and tadalafil, a CYP3A4 substrate, may cause an increase in systemic concentrations of tadalafil. Use caution when administering these drugs concomitantly.
    Tafamidis: (Moderate) Caution is advised with the coadministration of tafamidis and pazopanib due to the potential for increased plasma concentrations of pazopanib increasing the risk of adverse effects. Pazopanib dose adjustment may be needed with coadministration. Pazopanib is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
    Tamoxifen: (Major) Coadministration of pazopanib with tamoxifen is not advised due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation. Pazopanib has been reported to prolong the QT interval. Tamoxifen has also been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have been described when tamoxifen is used at lower doses.
    Tamsulosin: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and tamsulosin, a CYP3A4 substrate, may cause an increase in systemic concentrations of tamsulosin. Use caution when administering these drugs concomitantly.
    Tedizolid: (Moderate) If possible, stop use of pazopanib temporarily during treatment with oral tedizolid. If coadministration cannot be avoided, closely monitor for pazopanib-associated adverse events. Pazopanib plasma concentrations may be increased when administered concurrently with oral tedizolid. Pazopanib is a substrate of the Breast Cancer Resistance Protein (BCRP); oral tedizolid inhibits BCRP in the intestine.
    Telaprevir: (Major) Avoid administering pazopanib with strong CYP3A4 inhibitors, such as telaprevir. If co-administration with a strong CYP3A4 inhibitor is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. The concomitant use of pazopanib, a weak CYP3A4 inhibitor and a CYP3A4 and P-glycoprotein (P-gp) substrate, and telaprevir, a CYP3A4 and P-gp inhibitor and a CYP3A4 and P-gp substrate, may result in altered pazopanib and/or telaprevir concentrations.
    Telavancin: (Major) Concurrent use of pazopanib and telavancin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be coadministered, closely monitor the patient for QT interval prolongation. Both pazopanib and telavancin have been reported to prolong the QT interval.
    Telithromycin: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and telithromycin have been reported to prolong the QT interval. If pazopanib and telithromycin must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a substrate for CYP3A4 and P-glycoprotein (P-gp). Telithromycin is an inhibitor of CYP3A4 and P-gp. Concurrent administration of telithromycin and pazopanib may result in increased pazopanib concentrations; avoid use of these agents together if possible. If co-administration with a strong CYP3A4 inhibitor is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur.
    Telmisartan; Amlodipine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and amlodipine, a CYP3A4 substrate, may cause an increase in systemic concentrations of amlodipine. Use caution when administering these drugs concomitantly.
    Teniposide: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and teniposide, a CYP3A4 substrate, may cause an increase in systemic concentrations of teniposide. Use caution when administering these drugs concomitantly.
    Tepotinib: (Major) Avoid coadministration of pazopanib and tepotinib due to the potential for increased pazopanib exposure. Pazopanib is a P-gp substrate; tepotinib is a P-gp inhibitor. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit P-gp.
    Tetrabenazine: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as tetrabenazine, is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and tetrabenazine must be continued, closely monitor the patient for QT interval prolongation.
    Theophylline, Aminophylline: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and theophylline, aminophylline, a CYP3A4 substrate, may cause an increase in systemic concentrations of theophylline, aminophylline. Use caution when administering these drugs concomitantly.
    Thioridazine: (Contraindicated) Pazopanib has been reported to prolong the QT interval. Because of the potential for torsade de pointes (TdP), use of tthioridazine with pazopanib is contraindicated.
    Tiagabine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and tiagabine, a CYP3A4 substrate, may cause an increase in systemic concentrations of tiagabine. Use caution when administering these drugs concomitantly.
    Tipranavir: (Major) Avoid administering pazopanib with strong CYP3A4 inhibitors, such as tipranavir. If co-administration with a strong CYP3A4 inhibitor is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. The concomitant use of pazopanib, a weak CYP3A4 inhibitor and a CYP3A4 and P-glycoprotein (P-gp) substrate, and tipranavir, a strong CYP3A4 inhibitor, a CYP3A4 and P-gp substrate, and a P-gp inducer, may result in altered pazopanib and/or tipranavir concentrations.
    Tolterodine: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering pazopanib with tolterodine. Pazopanib is associated with QT prolongation. Tolterodine has also been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. In a small portion of patients who poorly metabolize tolterodine via CYP2D6, the CYP3A4 pathway becomes important in tolterodine elimination. Because it is difficult to assess which patients will be poor metabolizers of tolterodine via CYP2D6, those patients receiving CYP3A4 inhibitors, such as pazopanib, should be monitored closely for adverse events. Pharmacokinetic studies of the use of tolterodine concomitantly with CYP3A4 inhibitors have not been performed.
    Topiramate: (Moderate) Coadministration of pazopanib and topiramate may cause a decrease in systemic concentrations of pazopanib. Use caution when administering these drugs concomitantly. Pazopanib is a substrate for CYP3A4. Topiramate in a weak CYP3A4 inducer.
    Toremifene: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Pazopanib has also been reported to prolong the QT interval.
    Tramadol: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and tramadol, a CYP3A4 substrate, may cause an increase in systemic concentrations of tramadol. Use caution when administering these drugs concomitantly.
    Tramadol; Acetaminophen: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and tramadol, a CYP3A4 substrate, may cause an increase in systemic concentrations of tramadol. Use caution when administering these drugs concomitantly.
    Trandolapril; Verapamil: (Moderate) Pazopanib is a weak inhibitor of and substrate for CYP3A4 and P-glycoprotein (P-gp). Verapamil is a substrate for and an inhibitor of CYP3A4 and P-gp. Concurrent administration may result in increased pazopanib concentrations and/or increased verapamil concentrations. Dose reduction of pazopanib should be considered when coadministration of pazopanib and verapamil is necessary.
    Trazodone: (Major) Avoid coadministration of trazodone and pazopanib. Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are post-marketing reports of torsade de pointes (TdP). Therefore, the manufacturer recommends avoiding trazodone in patients receiving other drugs that increase the QT interval. Pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Pazopanib is also a weak inhibitor of CYP3A4. Coadministration of pazopanib and trazodone, a CYP3A4 substrate, may cause an increase in systemic concentrations of trazodone.
    Triazolam: (Moderate) Monitor for signs of triazolam toxicity during coadministration with pazopanib and consider appropriate dose reduction of triazolam if clinically indicated. Coadministration may increase triazolam exposure. Triazolam is a sensitive CYP3A substrate and pazopanib is a weak CYP3A inhibitor.
    Triclabendazole: (Major) Coadministration of triclabendazole and pazopanib is not recommended due to the risk of additive QT prolongation. Monitor the ECG for QT prolongation if coadministration is required. Pazopanib is associated with QT interval prolongation. Transient prolongation of the mean QTc interval was noted on the ECG recordings in dogs administered triclabendazole.
    Tricyclic antidepressants: (Minor) Coadministration of pazopanib and other drugs that prolong the QT interval, such as tricyclic antidepressants is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Amitriptyline, clomipramine and imipramine are CYP3A4 substrates. Coadministration of pazopanib may cause an increase in systemic concentrations of the tricyclic antidepressant. Use caution when administering these drugs concomitantly.
    Trifluoperazine: (Minor) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be avoided with pazopanib include trifluoperazine.
    Trimipramine: (Minor) Coadministration of pazopanib and other drugs that prolong the QT interval, such as tricyclic antidepressants is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Amitriptyline, clomipramine and imipramine are CYP3A4 substrates. Coadministration of pazopanib may cause an increase in systemic concentrations of the tricyclic antidepressant. Use caution when administering these drugs concomitantly.
    Triptorelin: (Major) Coadministration of pazopanib and triptorelin is not advised due to the risk of QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT interval prolongation. Pazopanib has been reported to prolong the QT interval. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Tucatinib: (Major) Avoid coadministration of pazopanib and tucatinib due to the potential for increased pazopanib exposure. Pazopanib is a CYP3A4 and P-gp substrate; tucatinib is a strong CYP3A4 inhibitor and P-gp inhibitor. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit P-gp.
    Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with pazopanib. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a CYP3A4 substrate; pazopanib is a weak CYP3A4 inhibitor.
    Vandetanib: (Major) Coadministration of vandetanib with pazopanib is not advised due to an increased risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Pazopanib has also been reported to prolong the QT interval.
    Vardenafil: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as vardenafil, is not advised; pazopanib has been reported to prolong the QT interval. Vardenafil is associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil can produce an increase in QTc interval. If pazopanib and vardenafil are coadministered, closely monitor the patient for QT interval prolongation.
    Vemurafenib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and vemurafenib have been reported to prolong the QT interval. If pazopanib and vemurafenib must be continued, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4 and a substrate for P-glycoprotein (P-gp). Vemurafenib is a substrate for CYP3A4 and an inhibitor of P-gp. Concurrent administration of vemurafenib and pazopanib may result in increased pazopanib and/or vemurafenib concentrations. Use caution when concurrent administration is necessary.
    Venlafaxine: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. Venlafaxine administration is associated with a possible risk of QT prolongation; torsades de pointes (TdP) has reported with post-marketing use. If pazopanib and venlafaxine must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and venlafaxine, a CYP3A4 substrate, may cause an increase in systemic concentrations of venlafaxine. Use caution when concurrent administration is necessary.
    Verapamil: (Moderate) Pazopanib is a weak inhibitor of and substrate for CYP3A4 and P-glycoprotein (P-gp). Verapamil is a substrate for and an inhibitor of CYP3A4 and P-gp. Concurrent administration may result in increased pazopanib concentrations and/or increased verapamil concentrations. Dose reduction of pazopanib should be considered when coadministration of pazopanib and verapamil is necessary.
    Vincristine Liposomal: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and vincristine, a CYP3A4 substrate, may cause an increase in systemic concentrations of vincristine. Use caution when administering these drugs concomitantly.
    Vincristine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and vincristine, a CYP3A4 substrate, may cause an increase in systemic concentrations of vincristine. Use caution when administering these drugs concomitantly.
    Vinorelbine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with pazopanib is necessary. Vinorelbine is a CYP3A4 substrate and pazopanib is a weak CYP3A4 inhibitor.
    Voclosporin: (Major) Avoid concomitant use of pazopanib and voclosporin due to the potential for increase pazopanib exposure and risk of additive QT prolongation. If concomitant use is necessary, monitor ECGs and electrolytes; correct hypokalemia, hypomagnesemia, and hypocalcemia. Pazopanib is a P-gp substrate that has been associated with QT prolongation. Voclosporin is a P-gp inhibitor that has been associated with QT prolongation with supratherapeutic doses.
    Voriconazole: (Major) Avoid concurrent administration of voriconazole and pazopanib due to increased pazopanib exposure and additive QT prolongation. If coadministration is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. Pazopanib is a CYP3A4 substrate that has been reported to prolong the QT interval. Voriconazole is a strong CYP3A4 inhibitor that has also been associated with rare cases of torsade de pointes, cardiac arrest, and sudden death.
    Vorinostat: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as vorinostat, is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and vorinostat must be continued, closely monitor the patient for QT interval prolongation.
    Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with pazopanib is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Pazopanib is a weak CYP3A4 inhibitor and the R-enantiomer of warfarin is a CYP3A4 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
    Yohimbine: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and yohimbine, a CYP3A4 substrate, may cause an increase in systemic concentrations of yohimbine. Use caution when administering these drugs concomitantly.
    Zafirlukast: (Moderate) Pazopanib is a substrate for CYP3A4 and CYP2C8. Zafirlukast is an inhibitor of CYP3A4 and CYP2C8. Concurrent administration may result in increased pazopanib concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and zafirlukast is required.
    Zileuton: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and zileuton, a CYP3A4 substrate, may cause an increase in systemic concentrations of zileuton. Use caution when administering these drugs concomitantly.
    Ziprasidone: (Major) Concomitant use of ziprasidone and pazopanib should be avoided due to the potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and ziprasidone must be continued, closely monitor the patient for QT interval prolongation.
    Zolpidem: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and zolpidem, a CYP3A4 substrate, may cause an increase in systemic concentrations of zolpidem. Use caution when administering these drugs concomitantly.
    Zonisamide: (Moderate) Coadministration of pazopanib and zonisamide may result in increased concentrations of both drugs. Pazopanib is a weak inhibitor of CYP3A4 and a substrate of P-glycoprotein (P-gp). Zonisamide is a weak inhibitor of P-gp and a substrate of CYP3A4. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when administering these drugs concomitantly.

    PREGNANCY AND LACTATION

    Pregnancy

    Pregnancy should be avoided by females of reproductive potential during pazopanib treatment and for at least 2 weeks after the last dose. Although there are no adequately controlled studies in pregnant women, pazopanib 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 pazopanib should be apprised of the potential hazard to the fetus. Teratogenicity and abortion were observed in rabbits and rats who were administered pazopanib (at doses that resulted in systemic exposures lower than those observed at the maximum human dose of 800 mg/day) during organogenesis. Cardiovascular malformations (e.g., retroesophageal subclavian artery, missing innominate artery, changes in the aortic arch) and incomplete or absent ossification were reported in rats; increased post-implantation loss and abortion occurred in rabbits.

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

    MECHANISM OF ACTION

    Pazopanib is an oral multikinase inhibitor of angiogenesis. Pazopanib inhibits vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, platelet-derived growth factor receptor (PDGFR)-alpha and -beta, fibroblast growth factor receptor (FGFR)-1 and -3, cytokine receptor (Kit), interleukin-2 receptor inducible T-cell kinase (Itk), leukocyte-specific protein tyrosine kinase (Lck), and transmembrane glycoprotein receptor tyrosine kinase (c-Fms). In vitro, pazopanib inhibited ligand-induced autophosphorylation of VEGFR-2, Kit, and PDGFR-beta receptors. In patients with clear cell renal cell cancer (RCC), the most common histology of RCC, inactivation of the von-Hippel Lindau (VHL) gene, is present. Suppression of this gene leads to upregulation of a number of hypoxia-induced genes including VEGF and PDGF. VEGF induces a mitogenic response upon binding to one of the VEGF receptors (VEGFR-1 to -3) on endothelial cells. Transforming growth factor-alpha (TGF-alpha) is also regulated by the VHL gene; TGF-alpha acts as a ligand for EGF receptor and stimulates the growth of epithelial cells of the proximal renal tubule, where most RCCs appear to start.

    PHARMACOKINETICS

    Pazopanib is administered orally. Pazopanib exhibits greater than 99% binding to human plasma protein in vivo, with no concentration dependence over the range of 10 to 100 mcg/mL. It has a mean elimination half-life of 31 hours. Elimination is primarily through the feces with a minor contribution from renal elimination (less than 4%).
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CYP1A2, CYP2C8, P-glycoprotein (P-gp), BCRP
    Pazopanib is metabolized primarily by CYP3A4 with a minor contribution from CYP1A2 and CYP2C8; in vitro studies also suggest that it is a substrate for P-gp and BCRP. Pazopanib is a weak inhibitor of CYP3A4, CYP2C8, CYP2D6, UGT1A1, and OATP1B1. In vitro studies with human liver microsomes showed that pazopanib inhibited the activities of CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP2E1. In vitro, it inhibits UGT1A1 and OATP1B1 with IC50s of 1.2 and 0.79 microMolar, respectively. Potential induction of CYP3A4 was demonstrated in an in vitro human pregnane X receptor (PXR) assay.

    Oral Route

    After oral administration, the median time to achieve peak concentrations of pazopanib (Tmax) is 2 to 4 hours after the dose. Doses of 800 mg once daily resulted in a mean AUC of 1,037 mcg/mL and a Cmax of 58.1 mcg/mL. Doses above 800 mg did not result in a consistent increase in AUC or Cmax. Administration of a crushed 400 mg tablet increased the AUC by 46% and increased the Cmax by approximately 2-fold compared to administration of a whole tablet; the Tmax decreased by approximately 2 hours.
     
    Systemic exposure to pazopanib is increased when it is administered with food. The AUC and Cmax were increased by approximately 2-fold when pazopanib was administered with a high-fat (approximately 50% fat) or low-fat (approximately 5% fat) meal. Coadministration with esomeprazole, a proton pump inhibitor, decreased the exposure of pazopanib by approximately 40% (AUC and Cmax).