Severe and fatal hepatotoxicity has been observed in clinical trials. Monitor hepatic function and interrupt, reduce, or discontinue dosing as recommended.
Note: Withhold pazopanib treatment for at least 1 week prior to elective surgery; do not administer pazopanib for at least 2 weeks after major surgery and until adequate wound healing.
Desmoid tumors, progressive (off-label use): Oral: 800 mg once daily until disease progression or unacceptable toxicity for up to a maximum of 1 year (Toulmonde 2019).
Renal cell carcinoma, advanced:
Note: May be used as initial therapy for patients with limited burden, favorable-risk disease who desire a more aggressive initial approach, for those with favorable-risk disease who are ineligible for immunotherapy-based combinations, or for those with progression after initial immunotherapy and who have not received prior VEGF treatment (George 2022).
Oral: 800 mg once daily until disease progression or unacceptable toxicity (Sternberg 2010).
Soft tissue sarcoma, advanced: Oral: 800 mg once daily until disease progression or unacceptable toxicity (Van Der Graaf 2012).
Thyroid cancer, advanced differentiated (off-label use): Oral: 800 mg once daily until disease progression or unacceptable toxicity (Bible 2010; Bible 2014).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult Drug Interactions database for more information.
Missed doses: If a dose is missed, do not take if less than 12 hours until the next dose.
Preexisting impairment: No dosage adjustment recommended. Pazopanib has not been studied in patients with severe impairment or in patients undergoing peritoneal dialysis or hemodialysis; however, pazopanib is not significantly eliminated renally. Hemodialysis is not expected to enhance pazopanib elimination.
Renal toxicity during treatment:
Proteinuria (≥3 g/24 hours): Withhold pazopanib until improvement to ≤ grade 1; resume at a reduced dose. Permanently discontinue pazopanib if 24-hour urine protein ≥3 g does not improve or recurs despite pazopanib dose reduction. Refer to "Dosing: Adjustment for Toxicity" for dose reduction levels.
Nephrotic syndrome (confirmed): Permanently discontinue pazopanib.
Preexisting impairment:
Mild (bilirubin ≤1.5 times ULN or ALT >ULN): No dosage adjustment required (Shibata 2013).
Moderate (bilirubin >1.5 to 3 times ULN and any ALT): Consider alternatives to pazopanib. If pazopanib is used, reduce dose to 200 mg once daily (maximum tolerated dose in patients with moderate hepatic impairment) (Shibata 2013).
Severe (bilirubin >3 times ULN with any ALT level): Use is not recommended.
Hepatotoxicity during treatment:
Isolated ALT elevations 3 to 8 times ULN: Continue pazopanib treatment, monitor liver function weekly until ALT returns to grade 1 or baseline.
Isolated ALT elevations >8 times ULN: Interrupt pazopanib treatment until improvement to grade 1 or baseline. If potential therapy benefit outweighs the risk of hepatotoxicity, resume pazopanib at a reduced dose not to exceed 400 mg once daily (with liver function monitored weekly for 8 weeks); permanently discontinue pazopanib if ALT >3 times ULN recurs despite dose reduction. Refer to "Dosing: Adjustment for Toxicity" for dose reduction levels.
ALT >3 times ULN concurrently with bilirubin >2 times ULN: Permanently discontinue pazopanib; continue to monitor until resolution.
Gilbert syndrome with only mild indirect (unconjugated) hyperbilirubinemia and ALT >3 times ULN: Manage as per isolated ALT elevations dosage recommendations above.
Refer to adult dosing.
|
Recommended Pazopanib Dose Reduction Levels for Adverse Reactions | ||
|---|---|---|
|
Dose reduction level |
Renal cell carcinoma |
Soft tissue sarcoma |
|
Usual (initial) dose |
800 mg once daily |
800 mg once daily |
|
First reduction |
400 mg once daily |
600 mg once daily |
|
Second reduction |
200 mg once daily |
400 mg once daily |
|
Permanently discontinue pazopanib if unable to tolerate the second dose reduction. | ||
|
Recommended Pazopanib Dosage Modifications for Adverse Reactions | ||
|---|---|---|
|
Adverse reaction |
Severity |
Pazopanib dosage modification |
|
Cardiotoxicity: Left ventricular systolic dysfunction |
Symptomatic or grade 3 |
Withhold pazopanib until improvement to < grade 3; resume pazopanib treatment based on clinical judgement. |
|
Grade 4 |
Permanently discontinue pazopanib. | |
|
GI perforation |
Any grade |
Permanently discontinue pazopanib. |
|
GI fistula |
Grade 2 or 3 |
Withhold pazopanib and resume based on clinical judgement. |
|
Grade 4 |
Permanently discontinue pazopanib. | |
|
Hemorrhagic events |
Grade 2 |
Withhold pazopanib until improvement to ≤ grade 1; then resume pazopanib at a reduced dose. Discontinue pazopanib permanently if grade 2 hemorrhage recurs after pazopanib treatment interruption and dose reduction. |
|
Grade 3 or 4 |
Permanently discontinue pazopanib. | |
|
Hypertension |
Grade 2 or 3 |
Reduce pazopanib dose and initiate or adjust antihypertensive therapy. Permanently discontinue pazopanib if hypertension remains at grade 3 despite pazopanib dose reduction and adjustment of antihypertensive therapy. |
|
Grade 4 or hypertensive crisis |
Permanently discontinue pazopanib. | |
|
Hypothyroidism |
n/a |
Manage hypothyroidism as appropriate. |
|
Infection |
Serious |
Institute appropriate anti-infective therapy promptly and consider pazopanib interruption or discontinuation. |
|
Posterior reversible encephalopathy syndrome |
Any grade |
Permanently discontinue pazopanib. |
|
Pulmonary toxicity: Interstitial lung disease |
Any grade |
Permanently discontinue pazopanib. |
|
Thrombosis: Arterial thrombotic events |
Any grade |
Permanently discontinue pazopanib. |
|
Thrombosis: Venous thrombotic events |
Grade 3 |
Withhold pazopanib; resume pazopanib at the same dose if managed with appropriate therapy for at least 1 week. |
|
Grade 4 |
Permanently discontinue pazopanib. | |
|
Thrombotic microangiopathy |
Any grade |
Permanently discontinue pazopanib. |
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Votrient: 200 mg
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Votrient: 200 mg
Generic: 200 mg
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/022465s031s032lbl.pdf#page=27, must be dispensed with this medication.
Oral: Administer on an empty stomach, 1 hour before or 2 hours after a meal. Swallow tablets whole; do not crush (rate of absorption may be increased; may affect systemic exposure).
If concurrent use of a gastric acid-reducing agent cannot be avoided, consider short-acting antacids in place of proton pump inhibitors and H2-receptor antagonists; separate pazopanib administration from short-acting antacids by several hours.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Renal cell carcinoma, advanced: Treatment of advanced renal cell carcinoma in adults.
Soft tissue sarcoma, advanced: Treatment of advanced soft tissue sarcoma in adults who have received prior chemotherapy.
Limitations of use: The efficacy of pazopanib for the treatment of adipocytic soft tissue sarcoma or gastrointestinal stromal tumors (GIST) has not been demonstrated.
Desmoid tumors (progressive); Thyroid cancer (advanced, differentiated)
PAZOPanib may be confused with axitinib, palbociclib, panobinostat, pegaptanib, pemigatinib, pexidartinib, PONATinib, pralsetinib, regorafenib, SUNItinib, tivozanib, vandetanib
Votrient may be confused with vorinostat
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Bradycardia (2% to 19%), cardiac insufficiency (11% to 13%), hypertension (40% to 42%), peripheral edema (14%)
Dermatologic: Alopecia (8% to 12%), exfoliative dermatitis (18%), hair discoloration (38% to 39%), hypopigmentation (11%), palmar-plantar erythrodysesthesia (6% to 11%)
Endocrine & metabolic: Decreased serum albumin (34%), decreased serum glucose (17%), decreased serum magnesium (26%), decreased serum phosphate (34%), decreased serum sodium (31%), increased serum glucose (41% to 45%), increased serum potassium (16%), weight loss (9% to 48%)
Gastrointestinal: Abdominal pain (11%), anorexia (22%), decreased appetite (40%), diarrhea (52% to 59%), dysgeusia (8% to 28%), gastrointestinal pain (23%), nausea (26% to 56%), stomatitis (11% to 12%; grade 3: ≤2%), vomiting (21% to 33%)
Hematologic & oncologic: Hemorrhage (13% to 22%; grade 4: 1%), leukopenia (37% to 44%; grade 3: 1%), lymphocytopenia (31% to 43%; grade 3: 4% to 10%, grade 4: <1%), neutropenia (33% to 34%; grade 3: 1% to 4%, grade 4: <1%), thrombocytopenia (32% to 36%; grade 3: <1%, grade 4: ≤1%)
Hepatic: Increased serum alanine aminotransferase (46% to 53%; >10 x ULN: 4%), increased serum alkaline phosphatase (32%), increased serum aspartate aminotransferase (51% to 53%), increased serum bilirubin (29% to 36%)
Nervous system: Dizziness (11%), fatigue (19% to 65%), headache (10% to 23%), tumor pain (29%)
Neuromuscular & skeletal: Asthenia (14%), musculoskeletal pain (23%), myalgia (23%)
Respiratory: Cough (17%), dyspnea (20%)
1% to 10%:
Cardiovascular: Acute myocardial infarction (≤2%), cardiac failure (≤1%), chest pain (5% to 10%), facial edema (1%), ischemia (≤2%), left ventricular systolic dysfunction (8%), prolonged QT interval on ECG (2%), transient ischemic attacks (1%), venous thrombosis (1% to 5%)
Dermatologic: Nail disease (5%), skin depigmentation (3%), skin rash (8%), xeroderma (6%)
Endocrine & metabolic: Hypothyroidism (4% to 8%)
Gastrointestinal: Anal hemorrhage (2%), dyspepsia (5% to 7%), gastrointestinal fistula (≤1%), gastrointestinal perforation (≤1%), increased serum lipase (4%), pancreatitis
Genitourinary: Hematuria (4%), proteinuria (1% to 9%)
Hematologic & oncologic: Oral hemorrhage (3%), rectal hemorrhage (1%)
Nervous system: Chills (5%), insomnia (9%), voice disorder (4% to 8%)
Ophthalmic: Blurred vision (5%)
Respiratory: Epistaxis (2% to 8%), hemoptysis (2%), pneumothorax (≤3%)
<1%:
Cardiovascular: Cerebrovascular accident, subarachnoid hemorrhage, torsades de pointes
Genitourinary: Nephrotic syndrome
Nervous system: Cerebral hemorrhage, intracranial hemorrhage
Pulmonary: Interstitial pulmonary disease, pneumonitis
Frequency not defined:
Cardiovascular: Decreased left ventricular ejection fraction, hypertensive crisis
Gastrointestinal: Gastrointestinal hemorrhage (including peritoneal hemorrhage)
Genitourinary: Genitourinary tract hemorrhage
Hematologic & oncologic: Pulmonary hemorrhage, thrombotic microangiopathy (including hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura)
Hepatic: Severe hepatotoxicity
Neuromuscular & skeletal: Arthralgia, muscle spasm
Postmarketing:
Cardiovascular: Aneurysm (arterial), aortic aneurysm, aortic dissection, coronary artery dissection, myocardial rupture (arterial rupture, aortic rupture)
Hematologic & oncologic: Polycythemia, tumor lysis syndrome
Infection: Serious infection
Nervous system: Reversible posterior leukoencephalopathy syndrome
Ophthalmic: Retinal changes (tear), retinal detachment
There are no contraindications listed in the manufacturer’s US labeling.
Canadian labeling: Hypersensitivity to pazopanib or any component of the formulation; use in pediatric patients <2 years of age (due to the antiangiogenic effects)
Concerns related to adverse effects:
• Cardiotoxicity: Cardiac dysfunction (including decreased left ventricular ejection fraction [LVEF] and heart failure) have been reported with pazopanib, in studies both with and without routine on-study LVEF monitoring. Myocardial dysfunction, defined as symptoms of cardiac dysfunction, or ≥15% absolute decline in LVEF (from baseline), or a decline in LVEF of ≥10% (from baseline) that is also below the lower limit of normal, has also been reported. Most patients with pazopanib-related myocardial dysfunction had concurrent hypertension, which may have exacerbated cardiac dysfunction in patients at risk (eg, prior anthracycline therapy) possibly by increasing cardiac afterload; monitor BP and manage as appropriate. If indicated, initiate appropriate antihypertensive treatment to reduce the risk for cardiotoxicity (ASCO [Armenian 2017]). Monitor for clinical signs/symptoms of heart failure. Evaluate LVEF at baseline and periodically in patients at risk of cardiac dysfunction (including prior anthracycline exposure). Depending on the severity of cardiac dysfunction, withhold or permanently discontinue pazopanib.
• GI perforation/fistula: Perforation and fistula (including fatal events) have been reported with pazopanib (rare). Monitor for signs/symptoms of GI perforation and fistula. Withhold pazopanib for grade 2 or 3 GI fistula (resume based on clinical judgement). Permanently discontinue pazopanib for GI perforation or grade 4 GI fistula.
• Hand-foot skin reaction: Hand-foot skin reaction (HFSR) observed with tyrosine kinase inhibitors (TKIs) is distinct from hand-foot syndrome (palmar-plantar erythrodysesthesia) associated with traditional chemotherapy agents. HFSR due to TKIs is localized with defined hyperkeratotic lesions; symptoms include burning, dysesthesia, paresthesia, or tingling of the palms/soles, and generally occur within the first 2 to 4 weeks of treatment. Pressure and flexor areas may develop blisters (callus-like), dry/cracked skin, edema, erythema, desquamation, or hyperkeratosis. The incidence of HFSR is lower with pazopanib (compared to other tyrosine kinase inhibitors). Examine skin at baseline (remove calluses with pedicure prior to treatment) and with each visit; apply an emollient based moisturizer twice daily during treatment. If HFSR develops, consider changing moisturizer to a urea-based product; topical steroids may be utilized for the anti-inflammatory effect; avoid excessive friction or pressure to affected areas and avoid restrictive footwear. Temporary dose reduction or treatment interruption may be necessary (Appleby 2011).
• Hemorrhage: Hemorrhagic events (including fatal events) have been reported. The most common events were hematuria, epistaxis, hemoptysis, anal/rectal hemorrhage, and mouth hemorrhage. Serious hemorrhagic events included pulmonary, GI, and genitourinary hemorrhage; cerebral/intracranial hemorrhage have been observed rarely. Patients with a history of hemoptysis, cerebral hemorrhage or clinically significant GI hemorrhage within 6 months were excluded from clinical trials. Depending on the hemorrhage severity, withhold (and resume at a reduced dose) or permanently discontinue pazopanib.
• Hepatotoxicity: [US Boxed Warning]: Severe and fatal hepatotoxicity (transaminase and bilirubin elevations) has been observed with pazopanib. Monitor hepatic function and interrupt treatment, reduce dose, or discontinue as recommended. Among clinical trials, ALT elevations of >3 to >10 times ULN have occurred; concurrent elevation in ALT > 3 times ULN and bilirubin >2 times ULN in the absence of significant alkaline phosphatase >3 times ULN has also been reported. Deaths due to hepatic failure have been described (rare). Monitor LFTs at baseline; at weeks 3, 5, 7, and 9; at months 3 and 4; then periodically as clinically indicated. If ALT elevation occurs, increase to weekly monitoring until ALT returns to grade 1 or baseline. Transaminase elevations usually occur early in the treatment course, with most elevations (any grade) occurring within the first 18 weeks. Based on the hepatotoxicity severity, withhold pazopanib (and resume at reduced dose with continued weekly monitoring for 8 weeks) or permanently discontinue pazopanib with weekly monitoring until resolution. Dosage reduction is recommended for preexisting moderate hepatic impairment; use is not recommended in patients with preexisting severe hepatic impairment. Mild indirect (unconjugated) hyperbilirubinemia may occur in patients with Gilbert syndrome (pazopanib is a UGT1A1 inhibitor); for patients with known Gilbert syndrome (only a mild indirect bilirubin elevation) and ALT >3 times ULN, follow the dosage modification recommendations for isolated ALT elevations. Patients >65 years of age are at a higher risk for hepatotoxicity. Concomitant use of pazopanib and simvastatin increases the risk of ALT elevations; insufficient data are available to assess the risk of concomitant administration of alternative statins and pazopanib.
• Hypertension: Pazopanib may cause and/or worsen hypertension (systolic BP ≥150 mm Hg or diastolic BP ≥100 mm Hg); hypertensive crisis has been observed. Approximately 40% of patients experienced hypertension; grade 3 hypertension occurred in some patients. Most cases occurred within the initial 18 weeks of pazopanib treatment, while ~40% of cases occurred by day 9. A small percentage of patients required permanent pazopanib discontinuation due to hypertension. Optimize blood pressure prior to pazopanib initiation; do not initiate pazopanib in patients with uncontrolled hypertension. Monitor BP as clinically indicated and initiate/adjust antihypertensives as clinically indicated. Based on the hypertension severity, withhold pazopanib (and then reduce the dose) or permanently discontinue pazopanib.
• Infections: Serious, including fatal, infections (with and without neutropenia) have been reported; monitor for signs and symptoms of infection. Initiate appropriate anti-infection therapy and consider temporary pazopanib treatment interruption or discontinuation for serious infections.
• Ocular toxicity: Cases of retinal detachment/tear have been reported with pazopanib.
• Posterior reversible encephalopathy syndrome: Posterior reversible encephalopathy syndrome (PRES) has been reported (rarely) with pazopanib; may be fatal. PRES is a neurological disorder, which may present with headache, seizure, lethargy, confusion, blindness, and other visual and neurologic disturbances; mild to severe hypertension may also be present. Confirm PRES diagnosis with MRI. Permanently discontinue pazopanib in patients who develop PRES.
• Proteinuria: Proteinuria has been reported with pazopanib. Nephrotic syndrome has been observed rarely. Obtain baseline and periodic urinalysis during treatment and follow up with 24-hour urine protein when clinically indicated. Withhold pazopanib (and resume at a reduced dose) or permanently discontinue based on the severity of proteinuria. Permanently discontinue pazopanib for nephrotic syndrome.
• Pulmonary toxicity: Interstitial lung disease (ILD)/pneumonitis has been reported with pazopanib; may be fatal. Monitor for pulmonary symptoms which could indicate ILD/pneumonitis; permanently discontinue pazopanib if ILD or pneumonitis develop.
• QTc prolongation: QTc prolongation (≥500 msec), including torsades de pointes, has been observed with pazopanib (based on routine ECG monitoring). Monitor patients who are at significant risk of developing QTc prolongation, including patients with a history of QT prolongation, patients taking antiarrhythmics or other medications known to prolong the QT interval, or those with relevant preexisting cardiac disease. Obtain baseline and periodic ECGs; monitor (at baseline and as clinically indicated) and correct electrolyte (potassium, calcium, and magnesium) abnormalities prior to and during pazopanib treatment.
• Skin depigmentation: Depigmentation of the hair or skin may occur during pazopanib treatment.
• Thromboembolic events: Arterial thromboembolic events, including myocardial infarction, ischemia, cerebrovascular accident, or transient ischemic attack have been observed with pazopanib; some events were fatal. Patients who had an arterial thromboembolic event within the previous 6 months were excluded from clinical trials. Permanently discontinue pazopanib for arterial thromboembolic events. Venous thromboembolic events (VTEs), including venous thrombosis and pulmonary embolus (PE; some fatal) have occurred with pazopanib. Monitor for signs and symptoms of VTE and PE. Based on severity of the venous thromboembolic event, withhold pazopanib and then resume at same dose or permanently discontinue.
• Thrombotic microangiopathy: Thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), has been observed with pazopanib (as monotherapy or in combination with other anticancer agents). TMA typically occurs within 90 days of pazopanib initiation. Monitor for signs/symptoms of TMA; if TMA occurs, permanently discontinue pazopanib (and manage as clinically indicated). Improvement of TMA occurred after pazopanib was discontinued.
• Thyroid disorders: Hypothyroidism has been reported with pazopanib. Hypothyroidism was confirmed in studies based on a simultaneous rise of TSH and decline of T4. Monitor thyroid tests at baseline, during pazopanib treatment, and as clinically indicated. Manage hypothyroidism as appropriate.
• Tumor lysis syndrome: Cases of tumor lysis syndrome (TLS) have been reported with pazopanib (some fatal). Patients with rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration may be at higher risk for TLS. Monitor patients at risk closely and consider prophylactic treatment.
• Wound healing complications: Vascular endothelial growth factor receptor inhibitors are associated with impaired wound healing; therefore, pazopanib may affect wound healing. Withhold pazopanib treatment 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 treatment after resolution of wound healing complications has not been established.
Concurrent drug therapy issues:
• Combination therapy: Increased toxicity and mortality has been observed in trials evaluating concurrent use of pazopanib with other anticancer agents (pemetrexed, lapatinib)
• Drug-drug/drug-food interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
• East Asian patients: In an analysis of pooled clinical trials, grade 3 and 4 neutropenia, thrombocytopenia, and palmar-plantar erythrodysesthesia syndrome (hand-foot syndrome) were more frequently observed in patients of East Asian descent, compared to patients of non-East Asian descent.
• Older adult: Patients ≥65 years of age experienced increased incidences of grade 3 or 4 fatigue, hypertension, decreased appetite, and transaminase elevations and are at increased risk for hepatotoxicity (compared to younger patients).
• Pediatric: Based on the mechanism of action, organ growth and maturation may be affected during early postnatal development. May potentially cause serious adverse effects on organ development, particularly in children <2 years of age. Pazopanib is not approved for use in pediatric patients.
• Pharmacogenomic variation: A pooled analysis of TA repeat polymorphism of UGT1A1 showed a statistically significant increase of hyperbilirubinemia in patients with the (TA)7/TA7 genotype (UGT1A1*28/*28), relative to the (TA)6/(TA)6 and (TA6/(TA)7 genotypes. In a large pooled analysis, grade 2 and 3 ALT elevations (ALT >3 to <20 times ULN) were observed more frequently in patients carrying the HLA-B*57:01 allele versus noncarriers.
Substrate of BCRP/ABCG2, CYP1A2 (minor), CYP2C8 (minor), CYP3A4 (major), P-glycoprotein/ABCB1 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C8 (weak), CYP3A4 (weak), UGT1A1
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy
Amiodarone: May enhance the QTc-prolonging effect of PAZOPanib. Amiodarone may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy
Androgens: Hypertension-Associated Agents may enhance the hypertensive effect of Androgens. Risk C: Monitor therapy
Antacids: May decrease the serum concentration of PAZOPanib. Management: Avoid the use of antacids in combination with pazopanib whenever possible. Separate doses by several hours if antacid treatment is considered necessary. The impact of dose separation has not been investigated. Risk D: Consider therapy modification
Asciminib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Azithromycin (Systemic): May enhance the QTc-prolonging effect of PAZOPanib. Azithromycin (Systemic) may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
BCRP/ABCG2 Inhibitors: May increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Belinostat: UGT1A1 Inhibitors may increase the serum concentration of Belinostat. Risk X: Avoid combination
Bisphosphonate Derivatives: Angiogenesis Inhibitors (Systemic) may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Specifically, the risk for osteonecrosis of the jaw may be increased. Risk C: Monitor therapy
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Clarithromycin: May enhance the QTc-prolonging effect of PAZOPanib. Clarithromycin may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CloZAPine: May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of PAZOPanib. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of PAZOPanib. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of PAZOPanib. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of PAZOPanib. Management: Avoid concurrent use of pazopanib with strong inhibitors of CYP3A4 whenever possible. If it is not possible to avoid such a combination, reduce pazopanib dose to 400 mg. Further dose reductions may also be required if adverse reactions occur. Risk D: Consider therapy modification
Dabrafenib: May enhance the QTc-prolonging effect of PAZOPanib. Dabrafenib may decrease the serum concentration of PAZOPanib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Also monitor for reduced pazopanib efficacy. Risk C: Monitor therapy
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Dronedarone: May enhance the QTc-prolonging effect of PAZOPanib. Dronedarone may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Encorafenib: May enhance the QTc-prolonging effect of PAZOPanib. Encorafenib may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Management: If coadministration with these narrow therapeutic index/sensitive P-gp substrates is unavoidable, separate erdafitinib administration by at least 6 hours before or after administration of these P-gp substrates. Risk D: Consider therapy modification
Erythromycin (Systemic): May enhance the QTc-prolonging effect of PAZOPanib. Erythromycin (Systemic) may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy
Fluorouracil Products: May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Futibatinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Futibatinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Gilteritinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Gilteritinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Grapefruit Juice: May increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Haloperidol: QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Histamine H2 Receptor Antagonists: May decrease the serum concentration of PAZOPanib. Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Inhibitors of the Proton Pump (PPIs and PCABs): May decrease the serum concentration of PAZOPanib. Risk X: Avoid combination
Irinotecan Products: UGT1A1 Inhibitors may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, concentrations of SN-38 may be increased. UGT1A1 Inhibitors may increase the serum concentration of Irinotecan Products. Risk X: Avoid combination
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy
Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Lefamulin: May enhance the QTc-prolonging effect of QT-prolonging CYP3A4 Substrates. Management: Do not use lefamulin tablets with QT-prolonging CYP3A4 substrates. Lefamulin prescribing information lists this combination as contraindicated. Risk X: Avoid combination
Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider therapy modification
Levoketoconazole: May enhance the QTc-prolonging effect of PAZOPanib. Levoketoconazole may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider therapy modification
Lonafarnib: May increase the serum concentration of PAZOPanib. PAZOPanib may increase the serum concentration of Lonafarnib. Management: Avoid concurrent use of pazopanib with lonafarnib whenever possible. If combined, reduce pazopanib dose to 400 mg and reduce the lonafarnib dose to115 mg/m2 (or continue lonafarnib at a dose of 115 mg/m2). Monitor for toxicities. Risk D: Consider therapy modification
Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy
Midostaurin: May enhance the QTc-prolonging effect of PAZOPanib. Midostaurin may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Mitapivat: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
OLANZapine: May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Ondansetron: May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Osimertinib: May enhance the QTc-prolonging effect of PAZOPanib. Osimertinib may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Pacritinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Pacritinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Pentamidine (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Posaconazole: May increase the serum concentration of QT-prolonging CYP3A4 Substrates. Such increases may lead to a greater risk for proarrhythmic effects and other similar toxicities. Risk X: Avoid combination
Propafenone: May enhance the QTc-prolonging effect of PAZOPanib. Propafenone may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of PAZOPanib. Risk X: Avoid combination
QT-prolonging Antidepressants (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Antipsychotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the QTc-prolonging effect of PAZOPanib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-Prolonging Inhalational Anesthetics (Moderate Risk): QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Kinase Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of PAZOPanib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Miscellaneous Agents (Moderate Risk): QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of PAZOPanib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of PAZOPanib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Quinolone Antibiotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of PAZOPanib. QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk) may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of PAZOPanib. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
QuiNIDine: May enhance the QTc-prolonging effect of PAZOPanib. QuiNIDine may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
QuiNINE: May enhance the QTc-prolonging effect of PAZOPanib. QuiNINE may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Repaglinide: CYP2C8 Inhibitors (Weak) may increase the serum concentration of Repaglinide. Risk C: Monitor therapy
RisperiDONE: QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of RisperiDONE. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sacituzumab Govitecan: UGT1A1 Inhibitors may increase serum concentrations of the active metabolite(s) of Sacituzumab Govitecan. Specifically, concentrations of SN-38 may be increased. Risk X: Avoid combination
Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Weak) may increase the serum concentration of Simvastatin. Risk C: Monitor therapy
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: Consider therapy modification
Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Risk C: Monitor therapy
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy
Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Taurursodiol: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Taurursodiol: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider therapy modification
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Vemurafenib: May enhance the QTc-prolonging effect of PAZOPanib. Vemurafenib may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Vinflunine: PAZOPanib may enhance the adverse/toxic effect of Vinflunine. Risk C: Monitor therapy
Voxilaprevir: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Systemic exposure of pazopanib is increased when administered with food (AUC two-fold higher with a high-fat [~50% fat] or low-fat [~5% fat] meal). Grapefruit juice may increase the levels/effects of pazopanib. Management: Take on an empty stomach 1 hour before or 2 hours after a meal. Maintain adequate nutrition and hydration, unless instructed to restrict fluid intake. Avoid grapefruit/grapefruit juice.
Evaluate pregnancy status prior to treatment initiation in females of reproductive potential. Females of reproductive potential should use effective contraception during therapy and for at least 2 weeks after the last pazopanib dose. Male patients (including vasectomized patients) with female partners of reproductive potential should use condoms during treatment and for at least 2 weeks after the last pazopanib dose.
Transient amenorrhea has been described in a patient on pazopanib monotherapy; normal menses resumed 2 months after pazopanib treatment was discontinued (De Sanctis 2019).
Based on data from animal reproduction studies and the mechanism of action, in utero exposure to pazopanib may cause fetal harm.
It is not known if pazopanib is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends discontinuing breastfeeding during treatment and for 2 weeks after the last pazopanib dose.
Avoid grapefruit juice.
Monitor LFTs (ALT, AST, bilirubin) at baseline; at weeks 3, 5, 7, and 9; at months 3 and 4; then periodically as clinically indicated; if ALT elevation occurs, increase to weekly monitoring until ALT returns to grade 1 or baseline. Monitor serum electrolytes (eg, calcium, magnesium, potassium) at baseline and as clinically indicated; urinalysis for proteinuria at baseline and periodically during treatment (follow up with 24-hour urine protein when clinically indicated); thyroid function (TSH and T4 at baseline and TSH every 6 to 8 weeks during treatment [Appleby 2011]). Verify pregnancy status (in females of reproductive potential) prior to therapy initiation. Monitor BP as clinically indicated. Monitor patients who are at significant risk of developing QT prolongation with baseline and periodic ECGs. Evaluate left ventricular ejection fraction (LVEF) at baseline and periodically in patients at risk of cardiac dysfunction. Monitor for clinical signs/symptoms of heart failure, signs/symptoms of GI perforation or fistula, hand-foot skin reaction, hemorrhage, hepatotoxicity, infection, interstitial lung disease/pneumonitis, posterior reversible encephalopathy syndrome, thromboembolic events (VTE and PE), thrombotic microangiopathy, tumor lysis syndrome, and/or wound healing complications. Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Pazopanib is a tyrosine kinase (multikinase) inhibitor; limits tumor growth via inhibition of angiogenesis by inhibiting cell surface vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, VEGFR-3), platelet-derived growth factor receptors (PDGFR-alpha and -beta), fibroblast growth factor receptor (FGFR-1 and -3), cytokine receptor (cKIT), interleukin-2 receptor inducible T-cell kinase, lymphocyte-specific protein tyrosine kinase (Lck), and transmembrane glycoprotein receptor tyrosine kinase (c-Fms).
Protein binding: >99%.
Metabolism: Hepatic; primarily via CYP3A4, minor metabolism via CYP1A2 and CYP2C8.
Bioavailability: The AUC and Cmax are increased by ~2-fold with a meal (high-fat or low-fat). If tablets are crushed, the AUC is increased by 46%, the Cmax is increased by 2-fold, and the Tmax is decreased by ~2 hours (do not crush tablets).
Half-life elimination: ~31 hours.
Time to peak, plasma: 2 to 4 hours.
Excretion: Feces (primarily); urine (<4%).
Hepatic function impairment: The median steady state Cmax and AUC in patients with moderate impairment (total bilirubin 1.5 to 3 times ULN and any ALT) administered a 200 mg dose were ~43% and ~29%, respectively, of the median values following administration of an 800 mg dose in patients with normal hepatic function. The median steady state Cmax and AUC in patients with severe impairment (total bilirubin >3 times ULN and any ALT) administered a 200 mg dose were ~18% and ~15%, respectively, of the median values after administration of an 800 mg dose in patients with normal hepatic function.
Tablets (Votrient Oral)
200 mg (per each): $153.57
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