Pazopanib is an active pharmaceutical ingredient in the Other Protein Kinase Inhibitors group (L01EX). The information below is compiled per regulator from the product labels on record, with direct links to the original documents.
GBOfficial regulatory label· revised February 20, 2026[1]
Renal cell carcinoma (RCC) Pazopanib is indicated in adults for the first-line treatment of advanced renal cell carcinoma (RCC) and for patients who have received prior cytokine therapy for advanced disease. Soft-tissue sarcoma (STS) Pazopanib is indicated for the treatment of adult patients with selective subtypes of advanced soft- tissue sarcoma (STS) who have received prior chemotherapy for metastatic disease or who have progressed within 12 months after (neo) adjuvant therapy.
1).
How to take
CACanada· Health Canada
3 products
Uses
CAOfficial regulatory label· revised March 22, 2025[2]
Metastatic Renal Cell Carcinoma VOTRIENT (pazopanib hydrochloride) is indicated for the treatment of patients with metastatic renal cell (clear cell) carcinoma (mRCC) as first-line systemic therapy or as second-line systemic therapy after treatment with cytokines for metastatic disease.
Approval of VOTRIENT in mRCC is based on significant progression-free survival benefit in patients with mRCC of good performance status (ECOG 0-1). Prolongation of overall survival was not demonstrated nor were quality-of-life differences shown between patients receiving VOTRIENT versus placebo in the pivotal phase III trial (see 14 CLINICAL TRIALS).
Soft Tissue Sarcoma VOTRIENT (pazopanib hydrochloride) is indicated for the treatment of adult patients with selective subtypes of advanced Soft Tissue Sarcoma (STS) who have received prior chemotherapy for metastatic disease or who have progressed within 12 months after (neo) adjuvant therapy.
USUnited States· FDA
2 products
Uses
USOfficial regulatory label· revised November 24, 2025[3]
1 INDICATIONS AND USAGE Pazopanib tablets are a kinase inhibitor indicated for the treatment of adults with: advanced renal cell carcinoma (RCC). 1 ) advanced soft tissue sarcoma (STS) who have received prior chemotherapy. 2 ) Limitations of Use: The efficacy of pazopanib tablets for the treatment of patients with adipocytic soft tissue sarcoma or gastrointestinal stromal tumors has not been demonstrated.
1 Renal Cell Carcinoma Pazopanib tablets are indicated for the treatment of adults with advanced renal cell carcinoma (RCC). 2 Soft Tissue Sarcoma Pazopanib tablets are indicated for the treatment of adults with advanced soft tissue sarcoma (STS) who have received prior chemotherapy.
Limitations of Use :
The efficacy of pazopanib tablets for the treatment of patients with adipocytic STS or gastrointestinal stromal tumors has not been demonstrated.
EUEuropean Union· EMA
1 product
Uses
EUOfficial regulatory label· revised October 28, 2025[4]
Renal cell carcinoma (RCC) Votrient is indicated in adults for the first-line treatment of advanced renal cell carcinoma (RCC) and for patients who have received prior cytokine therapy for advanced disease. Soft-tissue sarcoma (STS) Votrient is indicated for the treatment of adult patients with selective subtypes of advanced soft-tissue sarcoma (STS) who have received prior chemotherapy for metastatic disease or who have progressed within 12 months after (neo) adjuvant therapy.
1).
How to take
Drug interactions
Known interactions involving Pazopanib. Select one for details. This list is informational and not a complete interaction checker.
Showing 240 of 465. Type above to find a specific drug.
Interaction data compiled from DDInter (academic, CC-BY). Severity classification only - this is not a complete interaction checker and not medical advice.
[1]MHRA (UK) · PL068310393 · revised February 20, 2026
[2]Health Canada (DPD) · 02352303 · revised March 22, 2025
[3]FDA DailyMed · 115eb5bb-1403-fb… · revised November 24, 2025 [PDF]
[4]European Medicines Agency · EMEA/H/C/001141 · revised October 28, 2025
[5]OpenFDA adverse-event reports (US), 12 months ending June 4, 2026.
Information on this page is compiled from public regulatory records. Drugvu is not affiliated with any regulator or pharmaceutical manufacturer. This is not medical advice. Always consult a qualified healthcare professional.
GBOfficial regulatory label· revised February 20, 2026[1]
Pazopanib treatment should only be initiated by a physician experienced in the administration of anti-cancer medicinal products. Posology Adults The recommended dose of Pazopanib for the treatment of RCC or STS is 800 mg once daily.
Dose modifications Dose modification (decrease or increase) should be in 200 mg decrements or increments in a stepwise fashion based on individual tolerability in order to manage adverse reactions. The dose of Pazopanib should not exceed 800 mg.
3). The safety and efficacy of Pazopanib in children aged 2 to 18 years of age have not yet been established. 2 but no recommendation on a posology can be made. Elderly There are limited data on the use of Pazopanib in patients aged 65 years and older.
In the RCC studies of Pazopanib, overall no clinically significant differences in safety of Pazopanib were observed between subjects aged at least 65 years and younger subjects. Clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some elderly patients cannot be ruled out.
2). Therefore, no dose adjustment is required in patients with creatinine clearance above 30 ml/min. Caution is advised in patients with creatinine clearance below 30 ml/min as there is no experience of Pazopanib in this patient population.
2). 4). Administration of Pazopanib to patients with mild or moderate hepatic impairment should be undertaken with caution and close monitoring of tolerability. 5 x upper limit of normal (ULN) regardless of the ALT value). 2). Pazopanib is not recommended in patients with severe hepatic impairment (defined as total bilirubin >3 x ULN regardless of the ALT value).
4 for liver monitoring and dose modification for patients with drug- induced hepatotoxicity. Method of administration Pazopanib is for oral use. 2). 2).
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
GBOfficial regulatory label· Adverse reactions· revised February 20, 2026[1]
1). 1). The most important serious adverse reactions identified in the RCC or STS studies were transient ischaemic attack, ischaemic stroke, myocardial ischaemia, myocardial and cerebral infarction, cardiac dysfunction, gastrointestinal perforation and fistula, QT prolongation, Torsade de Pointes and pulmonary, gastrointestinal and cerebral haemorrhage, all adverse reactions being reported in <1% of treated patients.
Other important serious adverse reactions identified in STS studies included venous thromboembolic events, left ventricular dysfunction and pneumothorax. Fatal events that were considered possibly related to Pazopanib included gastrointestinal haemorrhage, pulmonary haemorrhage/haemoptysis, abnormal hepatic function, intestinal perforation and ischaemic stroke.
The most common adverse reactions (experienced by at least 10% of the patients) of any grade in the RCC and STS trials included: diarrhoea, hair colour change, skin hypopigmentation, exfoliative rash, hypertension, nausea, headache, fatigue, anorexia, vomiting, dysgeusia, stomatitis, weight decreased, pain, elevated alanine aminotransferase and elevated aspartate aminotransferase.
Adverse drug reactions, all grades, which were reported in RCC and STS subjects or during the post- marketing period are listed below by MedDRA body system organ class, frequency and grade of severity. The following convention has been utilised for the classification of frequency: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); and not known (cannot be estimated from the available data).
Categories have been assigned based on absolute frequencies in the clinical trial data. Post-marketing data on safety and tolerability across all Pazopanib clinical studies and from spontaneous reports have also been evaluated. Within each system organ class, adverse reactions with the same frequency are presented in order of decreasing seriousness.
03%) 1 0 Blood and lymphatic system disorders Rare Thrombotic microangiopathy (including thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome)† not known not known not known Endocrine disorders Common Hypothyroidism 83 (7%) 1 (<1%) 0 Very common Decreased appetitee 317 (28%) 14 (1%) 0 Hypophosphataemia 21 (2%) 7 (<1%) 0Common Dehydration 16 (1%) 5 (<1%) 0 Uncommon Hypomagnesaemia 10 (<1%) 0 0 Metabolism and nutrition disorders Not known Tumour lysis syndrome* not known not known not known Psychiatric disorders Common Insomnia 30 (3%) 0 0 Dysgeusiac 254 (22%) 1 (<1%) 0Very common Headache 122 (11%) 11 (<1%) 0 Dizziness 55 (5%) 3 (<1%) 1 (<1%) Lethargy 30 (3%) 3 (<1%) 0 Paraesthesia 20 (2%) 2 (<1%) 0 Common Peripheral sensory neuropathy 17 (1%) 0 0 Hypoaesthesia 8 (<1%) 0 0 Transient ischaemic attack 7 (<1%) 4 (<1%) 0 Somnolence 3 (<1%) 1 (<1%) 0 Cerebrovascular accident 2 (<1%) 1 (<1%) 1 (<1%) Uncommon Ischaemic stroke 2 (<1%) 0 1 (<1%) Nervous system disorders Rare Posterior reversible encephalopathy / reversible posterior leukoencephalopathy syndrome† not known not known not known Common Vision blurred 19 (2%) 1 (<1%) 0 Retinal detachment† 1 (<1%) 1 (<1%) 0 Retinal tear† 1 (<1%) 1 (<1%) 0Eye disorders Uncommon Eyelash discolouration 4 (<1%) 0 0 Bradycardia 6 (<1%) 0 0 Myocardial infarction 5 (<1%) 1 (<1%) 4 (<1%) Cardiac dysfunctionf 4 (<1%) 1 (<1%) 0 Cardiac disorders Uncommon Myocardial ischaemia 3 (<1%) 1 (<1%) 0 Very common Hypertension 473 (41%) 115 (10%) (<1%) Common Hot flush 16 (1%) 0 0 Venous thromboembolic eventg 13 (1%) 6 (<1%) 7 (<1%) Flushing 12 (1%) 0 0 Hypertensive crisis 6 (<1%) 0 2 (<1%)Uncommon Haemorrhage 1 (<1%) 0 0 Vascular disorders Rare Aneurysms and artery dissections† not known not known not known Epistaxis 50 (4%) 1 (<1%) 0 Dysphonia 48 (4%) 0 0 Dyspnoea 42 (4%) 8 (<1%) 1 (<1%) Common Haemoptysis 15 (1%) 1 (<1%) 0 Rhinorrhoea 8 (<1%) 0 0 Pulmonary haemorrhage 2 (<1%) 0 0 Uncommon Pneumothorax 1 (<1%) 0 0 Respiratory, thoracic and mediastinal disorders Rare Interstitial lung disease/pneumonitis† not known not known not known Diarrhoea 614 (53%) 65 (6%) 2 (<1%) Nausea 386 (34%) 14 (1%) 0 Vomiting 225 (20%) 18 (2%) 1 (<1%) Very common Abdominal paina 139 (12%) 15 (1%) 0 Stomatitis 96 (8%) 4 (<1%) 0 Dyspepsia 83 (7%) 2 (<1%) 0 Flatulence 43 (4%) 0 0 Abdominal distension 36 (3%) 2 (<1%) 0 Mouth ulceration 28 (2%) 3 (<1%) 0 Common Dry mouth 27 (2%) 0 0 Pancreatitis 8 (<1%) 4 (<1%) 0 Rectal haemorrhage 8 (<1%) 2 (<1%) 0 Haematochezia 6 (<1%) 0 0 Gastrointestinal haemorrhage 4 (<1%) 2 (<1%) 0 Melaena 4 (<1%) 1 (<1%) 0 Frequent bowel movements 3 (<1%) 0 0 Anal haemorrhage 2 […]
GBOfficial regulatory label· Warnings and precautions· revised February 20, 2026[1]
Hepatic effects Cases of hepatic failure (including fatalities) have been reported during use of Pazopanib. Administration of Pazopanib to patients with mild or moderate hepatic impairment should be undertaken with caution and close monitoring.
5 x ULN regardless of the ALT value). 2). 2). Exposure at a 200 mg dose is markedly reduced, though highly variable, in these patients, with values considered insufficient to obtain a clinically relevant effect. 8). In the majority of the cases, isolated increases in ALT and AST have been reported, without concomitant elevations of alkaline phosphatase or bilirubin.
Patients over 60 years of age may be at greater risk for mild (>3 x ULN) to severe (>8 x ULN) elevation of ALT. Patients who carry the HLA-B*57:01 allele have an increased risk of Pazopanib-associated ALT elevations. 1). Serum liver tests should be performed before initiation of treatment with Pazopanib, at weeks 3, 5, 7 and 9, then at months 3 and 4, with additional tests as clinically indicated.
Periodic testing should then continue after month 4. 5 x ULN and AST and ALT → 2 x ULN: Table 1 Dose modifications for drug-induced hepatotoxicity Liver test values Dose modification Transaminase elevation between 3 and 8 x ULN Continue on Pazopanib with weekly monitoring of liver function until transaminases return to Grade 1 or baseline.
Transaminase elevation of >8 x ULN Interrupt Pazopanib until transaminases return to Grade 1 or baseline. If the potential benefit of reinitiating Pazopanib treatment is considered to outweigh the risk for hepatotoxicity, then reintroduce Pazopanib at a reduced dose of 400 mg daily and perform serum liver tests weekly for 8 weeks.
Following reintroduction of Pazopanib, if transaminase elevations >3 x ULN recur, then Pazopanib should be permanently discontinued. Transaminase elevations >3 x ULN concurrently with bilirubin elevations >2 x ULN Permanently discontinue Pazopanib.
Patients should be monitored until return to Grade 1 or baseline. Pazopanib is a UGT1A1 inhibitor. Mild, indirect (unconjugated) hyperbilirubinaemia may occur in patients with Gilbert’s syndrome. Patients with only a mild indirect hyperbilirubinaemia, known or suspected Gilbert’s syndrome, and elevation in ALT >3 x ULN should be managed as per the recommendations outlined for isolated ALT elevations.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
GBOfficial regulatory label· Contraindications· revised February 20, 2026[1]
1.
This is not medical advice. Consult a qualified healthcare professional.
Patients were required to have disease progression on or after, or be intolerant to, an anthracycline-based regimen in the pivotal phase III study in STS. The pivotal phase III study in STS was designed to assess VOTRIENT in patients with selected tumour types including: fibroblastic, so-called fibrohistiocytic, leiomyosarcoma, malignant glomus tumours, skeletal muscles, vascular, uncertain differentiation (excluding chondrosarcoma, Ewing tumours / primitive neuroectodermal tumours), malignant peripheral nerve sheath tumours, and undifferentiated soft tissue sarcomas not otherwise specified.
However not all of the listed tumour types have been assessed in the clinical study (see 14 CLINICAL TRIALS). The efficacy and safety of VOTRIENT for the treatment of patients with other STS subtypes, including adipocytic STS (liposarcoma) and gastrointestinal stromal tumours (GIST), have not been demonstrated (see 7 WARNINGS AND PRECAUTIONS and 14 CLINICAL TRIALS).
Clinical effectiveness of VOTRIENT in STS is based on significant progression-free survival benefit in patients with advanced STS. Prolongation of overall survival was not demonstrated nor were quality-of-life differences shown between patients receiving VOTRIENT versus placebo in the pivotal phase III trial (see 14 CLINICAL TRIALS).
3 Pediatrics). Toxicology studies in rodents showed hypertrophy of epiphyseal growth plates and abnormalities in growing incisors and severe effects on body weight gain, organ growth and organ maturation during early post-natal development (see 16 NON-CLINICAL TOXICOLOGY).
VOTRIENT is not recommended for use in children and is contraindicated in children less than 2 years of age (see
How to take
CAOfficial regulatory label· revised March 22, 2025[2]
, Hepatic Impairment. 1 Dosing Considerations Dose modification, either an increase or decrease in dose, should be in 200 mg increments in a stepwise fashion based on individual tolerability in order to manage adverse reactions. The dose of VOTRIENT should not exceed 800 mg.
5 X ULN (with direct bilirubin >35%) and ALT elevations >2 X ULN, or who have moderate or severe hepatic impairment (Child-Pugh B and C). No formal studies have been carried out in patients with mild hepatic impairment and caution is recommended in these patients (see 10 CLINICAL PHARMACOLOGY; Special Populations and Conditions).
Renal Impairment:
No dose adjustments are recommended for patients with mild or moderate renal impairment. Patients with > 1 g protein (24 h collection) at baseline were excluded from the pivotal clinical studies. VOTRIENT is not recommended for patients with severe renal impairment (see 10 CLINICAL PHARMACOLOGY; Special Populations and Conditions).
Coadministration with strong CYP3A4 inhibitor:
If coadministration of a strong CYP3A4 inhibitor with VOTRIENT cannot be avoided, reduce the dose of VOTRIENT to 400 mg. Further dose reductions may be needed if adverse effects occur during therapy. 4 Drug-Drug Interactions - CYP3A4 Inhibitors).
Geriatrics:
No alteration of dosage, dosing frequency or route of administration is required in patients over 65 years. 2 Recommended Dose and Dosage Adjustment The recommended dose of VOTRIENT for the treatment of mRCC and STS is 800 mg orally once daily.
3 Pharmacokinetics). 4 Administration For oral use. 3 Pharmacokinetics). 5 Missed Dose If a dose is missed, VOTRIENT should not be taken if it is less than 12 hours until the next dose. Votrient (pazopanib hydrochloride) Product Monograph Page 7 of 54
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
CAOfficial regulatory label· Adverse reactions· revised March 22, 2025[2]
1 Adverse Reaction Overview The safety of VOTRIENT has been evaluated in more than 1600 patients in clinical trials including 977 patients in the monotherapy studies which include 586 mRCC patients. The mRCC data described below reflect exposure to VOTRIENT in 290 mRCC patients who participated in a randomized, double- blind, placebo-controlled study (VEG105192).
8 months for the placebo arm. Forty-two percent (42%) of patients on VOTRIENT required a dose interruption and thirty-six percent (36%) required a dose reduction. The safety and efficacy of VOTRIENT in soft tissue sarcoma (STS) were evaluated in a randomized, double-blind, placebo-controlled multi-centre study (VEG110727).
Patients (N = 369) with advanced STS who had received prior anthracycline treatment, or were unsuited for such therapy, were randomized to receive VOTRIENT 800 mg once daily (N = 246) or placebo (N = 123). 9 months for the placebo arm.
2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials may be Votrient (pazopanib hydrochloride) Product Monograph Page 17 of 54 useful in identifying and approximating rates of adverse drug reactions in real-world use. Potentially serious adverse reactions with VOTRIENT included hepatic effects, hypertension, QT prolongation and Torsade de Pointes, arterial and venous thrombotic events, cardiac dysfunction, hemorrhagic events and gastrointestinal perforation and fistula (see 7 WARNINGS AND PRECAUTIONS).
Other important serious adverse reactions identified in STS trials included venous thromboembolic events and pneumothorax. Metastatic Renal Cell Carcinoma Table 2 presents the most common adverse reactions occurring in ≥ 10 % of patients who received VOTRIENT in the pivotal mRCC study.
Table 2 Adverse Reactions Occurring in ≥10 % of mRCC Patients who Received VOTRIENT (Study VEG105192) VOTRIENT (N = 290) Placebo (N = 145) All Grades* Grade 3 Grade 4 All Grades* Grade 3 Grade 4 Reactions % % % % % % Gastrointestinal disorders Diarrhea 52 3 <1 9 <1 0 Nausea 26 <1 0 9 0 0 Vomiting 21 2 <1 8 2 0 Abdominal pain 11 2 0 1 0 0 Vascular disorders Hypertension 40 4 0 10 <1 0 General disorders and administrative site conditions Fatigue 19 2 0 8 1 1 Asthenia 14 3 0 8 0 0 Skin and subcutaneous tissue disorders Hair colour changes 38 <1 0 3 0 0 Metabolism and nutrition disorders Anorexia 22 2 0 10 <1 0 Nervous system disorder Headache 10 0 0 5 0 0 * National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.
b 27 of the 28 cases of skin disorder were palmar-plantar erythrodysesthesia. Votrient (pazopanib hydrochloride) Product Monograph Page 19 of 54 Metastatic Renal Cell Carcinoma and Soft Tissue Sarcoma Other adverse reactions observed more commonly in mRCC and STS patients treated with VOTRIENT with incidence more than 2% greater than placebo included: Bradycardia: Based on heart rate measurement (<60 beats per minute), asymptomatic bradycardia was observed in 12% (33/280) patients treated with VOTRIENT and in 8% (11/144) of patients on the placebo arm in the randomized RCC trial.
In the randomized trial of VOTRIENT for the treatment of STS, asymptomatic bradycardia was observed in 10% (24/238) of patients treated with VOTRIENT and in 2% (2/121) patients on the placebo arm. 1%) based on a review of the pazopanib clinical trials safety database.
Diarrhea:
Diarrhea occurred frequently and was predominantly mild to moderate in severity in both the RCC and STS clinical trials. Patients should be advised how to manage mild diarrhea and instructed to notify their healthcare provider if moderate to severe diarrhea occurs so appropriate management can be implemented to minimize this impact.
Amylase/Lipase Elevations:
In a single-arm mRCC phase II clinical study, increases in amylase values were observed for 42/184 patients (23%) and increases in lipase values were observed for 48/181 patients (27%). Increased blood amylase as an adverse reaction was reported for 6/225 patients (3%), all were Grade 1 or Grade 2 in severity.
Elevations in lipase as an adverse reaction were reported for 10 patients (4%) and were Grade 3 for 6 patients and Grade 4 for 1 patient. 7%).
Pneumothorax:
Two of 290 […]
CAOfficial regulatory label· Warnings and precautions· revised March 22, 2025[2]
3 Pediatrics 12/2021 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES............................................................................................
2 TABLE OF CONTENTS .............................................................................................................. 2 PART I: HEALTH PROFESSIONAL INFORMATION .....................................................................
6 5 OVERDOSAGE ............................................................................................................. 7 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ................................. 7 7 WARNINGS AND PRECAUTIONS ..................................................................................
1 Special Populations .......................................................................................... 1 Pregnant Women ....................................................................................... 2 Breast-feeding............................................................................................
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
CAOfficial regulatory label· Contraindications· revised March 22, 2025[2]
). 2 Geriatrics Geriatrics (65 years of age and over): In clinical trials with VOTRIENT for the treatment of mRCC, 196 patients (33%) were aged ≥65 years, and 34 patients (6%) were aged >75 years. In the STS clinical trials, 93 patients (24%) were aged 65 years, and 17 subjects (4%) were aged 75 years.
No overall differences in safety or effectiveness of VOTRIENT were observed between these patients and younger patients in clinical trials. However, a meta-analysis shows that patients over 60 years of age may be at greater risk for ALT >3 X ULN.
Although no other differences in responses between elderly and younger patients have been identified clinically; a greater sensitivity of some older individuals cannot be ruled out. 2 CONTRAINDICATIONS VOTRIENT (pazopanib hydrochloride) is contraindicated for: Patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.
For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION, AND PACKAGING section of the product monograph. Pediatric patients less than 2 year of age. VOTRIENT is an anti-angiogenic agent that severely affects body weight gain, organ growth and organ maturation during early post-natal development in rats (see 7 WARNINGS AND PRECAUTIONS and 16 NON-CLINICAL TOXICOLOGY).
This is not medical advice. Consult a qualified healthcare professional.
USOfficial regulatory label· revised November 24, 2025[3]
2 DOSAGE AND ADMINISTRATION Recommended Dosage: 800 mg orally once daily without food (at least 1 hour before or 2 hours after a meal). 1 ) Moderate Hepatic Impairment: 200 mg orally once daily. 3 )]. 4 )]. Swallow tablets whole. 3 )]. If a dose is missed, it should not be taken if it is <12 hours until the next dose.
2 Dosage Modifications for Adverse Reactions Table 1 summarizes the recommended dose reductions. Table 1. Recommended Dose Reductions of Pazopanib tablets for Adverse Reactions Dose Reduction For Renal Cell Carcinoma For Soft Tissue Sarcoma First 400 mg orally once daily 600 mg orally once daily Second 200 mg orally once daily 400 mg orally once daily Permanently discontinue pazopanib tablets in patients unable to tolerate the second dose reduction.
Table 2 summarizes the recommended dosage modifications for adverse reactions. Table 2. 1 )] Isolated ALT elevations between 3 x ULN and 8 x ULN Continue and monitor liver function weekly until ALT returns to Grade 1 or baseline. Isolated ALT elevations of > 8 x ULN Withhold until improvement to Grade 1 or baseline.
If the potential benefit for resuming treatment with pazopanib tablets is considered to outweigh the risk for hepatotoxicity, then resume at a reduced dose of no more than 400 mg once daily and measure serum liver tests weekly for 8 weeks.
Permanently discontinue if ALT elevations > 3 x ULN recur despite dose reduction(s). ALT elevations > 3 x ULN occur concurrently with bilirubin elevations > 2 x ULN Permanently discontinue and continue to monitor until resolution. Patients with only a mild, indirect (unconjugated) hyperbilirubinemia, known as Gilbert's syndrome, and ALT elevations > 3 x ULN should be managed per the recommendations outlined for isolated ALT elevations.
3 )] Symptomatic or Grade 3 Withhold until improvement to Grade < 3. Resume treatment based on medical judgement. Grade 4 Permanently discontinue. 4 )] Grade 2 Withhold until improvement to Grade ≤ 1. Resume at reduced dose (see Table 1).
Permanently discontinue if Grade 2 recurs after dose interruption and reduction. Grade 3 or 4 Permanently discontinue. 5 )] Any grade Permanently discontinue. 6 )] Grade 3 Withhold pazopanib tablets and resume at same dose if managed with appropriate therapy for at least one week.
Grade 4 Permanently discontinue. 7 ) ] Any grade Permanently discontinue. 8 )] Any grade Permanently discontinue. 8 ) ] Grade 2 or 3 Withhold and resume based on medical judgement. Grade 4 Permanently discontinue. 9 )] Any grade Permanently discontinue.
10 )] Any grade Permanently discontinue. 11 )] Grade 2 or 3 Reduce dose (see Table 1) and initiate or adjust anti-hypertensive therapy. Permanently discontinue if hypertension remains Grade 3 despite dose reduction(s) and adjustment of anti-hypertensive therapy.
Grade 4 or hypertensive crisis Permanently discontinue. 14 )] 24-hour urine protein ≥ 3 grams Confirmed nephrotic syndrome Withhold until improvement to Grade ≤ 1. Resume at a reduced dose (see Table 1). Permanently discontinue if 24-hour urine protein ≥ 3 grams does not improve or recurs despite dose reductions.
Permanently discontinue.
Abbreviations:
ALT, alanine aminotransferase; ULN, upper limit of normal. a National Cancer Institute Common Terminology Criteria for Adverse Events, version 5. 5 to 3 x upper limit of normal (ULN) and any alanine aminotransferase (ALT) value], consider alternatives to pazopanib tablets.
If pazopanib tablets are used in patients with moderate hepatic impairment, reduce the pazopanib tablets dose to 200 mg orally once daily. 7 )). 4 Dosage Modifications for Drug Interactions Strong CYP3A4 Inhibitors Avoid concomitant use of strong CYP3A4 inhibitors by use of an alternate concomitant medication with no or minimal potential to inhibit CYP3A4.
1 )]. Strong CYP3A4 Inducers Avoid concomitant use of strong CYP3A4 inducers by use of an alternate concomitant medication with no or minimal enzyme induction potential. 1 )]. Gastric Acid-Reducing Agents Avoid concomitant use of gastric acid-reducing agents.
If concomitant use of a gastric acid-reducing agent cannot be avoided, consider short-acting antacid in place of proton pump inhibitors (PPIs) and H 2 -receptor antagonists. 3 )].
This is not medical advice. Consult a qualified healthcare professional.
Most-reported reactions to the US regulator (12 mo to June 4, 2026): 245 reports total. [5]
Disease Progression 24
Malignant Neoplasm Progression 23
Drug Ineffective 22
Off Label Use 22
Death 18
Diarrhoea 15
Neoplasm Progression 15
Dizziness 11
Arthralgia 10
Cerebrovascular Accident 10
Arthritis 9
Balance Disorder 8
Side effects & warnings
USOfficial regulatory label· Adverse reactions· revised November 24, 2025[3]
16 )] The most common adverse reactions in patients with RCC (≥ 20%) are diarrhea, hypertension, hair color changes (depigmentation), nausea, anorexia, and vomiting. 1 ) The most common adverse reactions in patients with STS (≥ 20%) are fatigue, diarrhea, nausea, decreased weight, hypertension, decreased appetite, vomiting, tumor pain, hair color changes, musculoskeletal pain, headache, dysgeusia, dyspnea, and skin hypopigmentation.
1 ) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. gov/medwatch. 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described in the WARNINGS AND PRECAUTIONS section reflect exposure of 977 patients who received pazopanib tablets as a single agent, including 586 pazopanib-treated patients with RCC. 6) in these 977 patients, the most common adverse reactions (≥ 20%) in these 586 patients were diarrhea, hypertension, hair color change, nausea, fatigue, anorexia, and vomiting.
6 months (range, 0 to 53). The most common adverse reactions (≥ 20%) in these 382 patients were fatigue, diarrhea, nausea, decreased weight, hypertension, decreased appetite, vomiting, tumor pain, hair color changes, musculoskeletal pain, headache, dysgeusia, dyspnea, and skin hypopigmentation.
1 ). 4 months (range, 0 to 23) for patients who received pazopanib tablets. Forty-two percent of patients on pazopanib tablets required a dose interruption and 36% required a dose reduction. Table 3 presents adverse reactions in VEG105192.
a National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. Other adverse reactions observed more commonly in patients treated with pazopanib tablets than placebo and that occurred in < 10% (any grade) were alopecia (8% versus < 1%), chest pain (5% versus 1%), dysgeusia (8% versus < 1%), dyspepsia (5% versus < 1%), dysphonia (4% versus < 1%), facial edema (1% versus 0%), palmar-plantar erythrodysesthesia (6% versus < 1%), proteinuria (9% versus 0%), rash (8% versus 3%), skin depigmentation (3% versus 0%), and weight decreased (9% versus 3%).
a National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. Additional adverse reactions from other clinical trials in patients with RCC who received pazopanib tablets include arthralgia and muscle spasms.
2 )]. 5 months (range, 0 to 24) for patients who received pazopanib tablets. Fifty-eight percent of patients on pazopanib tablets required a dose interruption and 38% required a dose reduction. Seventeen percent of patients who received pazopanib tablets discontinued therapy due to adverse reactions.
a National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. b 27 of the 28 cases of skin disorder were palmar-plantar erythrodysesthesia. Other adverse reactions observed more commonly in patients treated with pazopanib tablets that occurred in ≥ 5% of patients and at an incidence of more than 2% difference from placebo included insomnia (9% versus 6%), hypothyroidism (8% versus 0%), dysphonia (8% versus 2%), epistaxis (8% versus 2%), left ventricular dysfunction (8% versus 4%), dyspepsia (7% versus 2%), dry skin (6% versus < 1%), chills (5% versus 1%), vision blurred (5% versus 2%), and nail disorder (5% versus 0%).
Table 6 presents the laboratory abnormalities in VEG110727. Table 6. Select Laboratory Abnormalities (> 10%) in Patients with STS Who Received Pazopanib Tablets with a Difference Between Arms of ≥ 5% Compared to Placebo in VEG110727 Parameters Pazopanib Tablets (N = 240) Placebo (N = 123) All Grades a Grade 3 Grade 4 All Grades a Grade 3 Grade 4 % % % % % % Chemistry AST increased 51 5 3 22 2 0 ALT increased 46 8 2 18 2 1 Glucose increased 45 < 1 0 35 2 0 Albumin decreased 34 1 0 21 0 0 Alkaline phosphataseincreased 32 3 0 23 1 0 Sodium decreased 31 4 0 20 3 0 Total bilirubin increased 29 1 0 7 2 0 Potassium increased 16 1 0 11 0 0 Hematologic Leukopenia 44 1 0 15 0 0 Lymphocytopenia 43 10 0 36 9 2 Thrombocytopenia 36 3 1 6 0 0 Neutropenia 33 4 0 7 0 0 Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; STS, soft tissue sarcoma.
a National Cancer Institute Common Terminology Criteria for Adverse Events, version 3 Other Clinically Relevant Adverse Reactions Lipase Elevations In a single-arm RCC trial (VEG102616), elevated lipase was observed for 27% of 181 patients with available laboratory data.
4% (1/225) with Grade 4. In the RCC trials, clinical pancreatitis was observed in < 1% of 586 patients. 3%) treated with pazopanib tablets in the randomized STS trial (VEG110727) developed a pneumothorax. Bradycardia In the randomized RCC trial (VEG105192), bradycardia based on vital signs (< 60 beats per minute) was observed in 19% of 280 patients treated with pazopanib tablets.
Bradycardia was reported as an adverse reaction in 2% of 290 patients. In the randomized STS trial (VEG110727), bradycardia based on vital signs (< 60 beats per minute) was observed in 19% of 238 patients treated with pazopanib tablets.
Bradycardia was reported as an adverse reaction in 2% of 240 patients. Adverse Reactions in East Asian Patients In an analysis of pooled clinical trial data (N = 1,938) with pazopanib tablets, Grade 3 and Grade 4 neutropenia (12% versus 2%), thrombocytopenia (6% versus < 1%) and palmar-plantar erythrodysesthesia (6% versus 2%) were observed more frequently in patients of East Asian descent than in patients of non-East Asian descent.
2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of pazopanib tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.
USOfficial regulatory label· Warnings and precautions· revised November 24, 2025[3]
5 WARNINGS AND PRECAUTIONS Hepatic Toxicity: Severe and fatal hepatotoxicity has occurred. Monitor liver tests at baseline, regularly during treatment and as clinically indicated. Withhold pazopanib tablets and resume at reduced dose with continued weekly monitoring for 8 weeks, or permanently discontinue with weekly monitoring until resolution based on severity of hepatotoxicity.
1 ) QT Prolongation and Torsades de Pointes: Monitor patients who are at significant risk of developing QT interval prolongation. Monitor electrocardiograms (ECGs) and electrolytes at baseline and as clinically indicated. Correct hypokalemia, hypomagnesemia, and hypocalcemia prior to initiating pazopanib tablets and during treatment.
2 ) Cardiac Dysfunction: Cardiac dysfunction, including decreased left ventricular ejection fraction (LVEF) and congestive heart failure, have occurred. Monitor blood pressure and manage as appropriate. Monitor for clinical signs or symptoms of congestive heart failure.
Conduct baseline and periodic evaluation of LVEF in patients at risk of cardiac dysfunction. Withhold or permanently discontinue pazopanib tablets based on severity of cardiac dysfunction. 3 ) Hemorrhagic Events: Fatal hemorrhagic events have occurred.
Pazopanib tablets have not been studied in patients who have a history of hemoptysis, cerebral hemorrhage, or clinically significant gastrointestinal hemorrhage in the past 6 months. Withhold pazopanib tablets and resume at reduced dose or permanently discontinue based on severity of hemorrhagic events.
4 ) Arterial Thromboembolic Events: Arterial thromboembolic events have been observed and can be fatal. Pazopanib tablets have not been studied in patients who have had an arterial thromboembolic event within the previous 6 months. Permanently discontinue pazopanib tablets in case of an arterial thromboembolic event.
5 ) Venous Thromboembolic Events: Venous thromboembolic events (VTEs) have been observed, including fatal pulmonary emboli (PE). Monitor for signs and symptoms of VTE and PE. Withhold pazopanib tablets and then resume at same dose or permanently discontinue based on severity of VTE.
6 ) Thrombotic Microangiopathy: Thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), has been observed. Permanently discontinue pazopanib tablets if TMA occurs. 7 ) Gastrointestinal Perforation and Fistula: Fatal perforation events have occurred.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
USOfficial regulatory label· Contraindications· revised November 24, 2025[3]
4 CONTRAINDICATIONS None. None. ( 4 )
This is not medical advice. Consult a qualified healthcare professional.
EUOfficial regulatory label· revised October 28, 2025[4]
Votrient treatment should only be initiated by a physician experienced in the administration of anti-cancer medicinal products. 3 Posology Adults The recommended dose of pazopanib for the treatment of RCC or STS is 800 mg once daily.
Dose modifications Dose modification (decrease or increase) should be in 200 mg decrements or increments in a stepwise fashion based on individual tolerability in order to manage adverse reactions. The dose of pazopanib should not exceed 800 mg.
3). The safety and efficacy of pazopanib in children aged 2 to 18 years of age have not yet been established. 2 but no recommendation on a posology can be made. Elderly There are limited data on the use of pazopanib in patients aged 65 years and older.
In the RCC studies of pazopanib, overall no clinically significant differences in safety of pazopanib were observed between subjects aged at least 65 years and younger subjects. Clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some elderly patients cannot be ruled out.
2). Therefore, no dose adjustment is required in patients with creatinine clearance above 30 ml/min. Caution is advised in patients with creatinine clearance below 30 ml/min as there is no experience of pazopanib in this patient population.
2). 4). Administration of pazopanib to patients with mild or moderate hepatic impairment should be undertaken with caution and close monitoring of tolerability. 5 x upper limit of normal (ULN) regardless of the ALT value). 2). Pazopanib is not recommended in patients with severe hepatic impairment (defined as total bilirubin >3 x ULN regardless of the ALT value).
4 for liver monitoring and dose modification for patients with drug-induced hepatotoxicity. Method of administration Pazopanib is for oral use. 2). 2). 4
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
EUOfficial regulatory label· Adverse reactions· revised October 28, 2025[4]
1). 1). The most important serious adverse reactions identified in the RCC or STS studies were transient ischaemic attack, ischaemic stroke, myocardial ischaemia, myocardial and cerebral infarction, cardiac dysfunction, gastrointestinal perforation and fistula, QT prolongation, Torsade de Pointes and pulmonary, gastrointestinal and cerebral haemorrhage, all adverse reactions being reported in <1% of treated patients.
Other important serious adverse reactions identified in STS studies included venous thromboembolic events, left ventricular dysfunction and pneumothorax. Fatal events that were considered possibly related to pazopanib included gastrointestinal haemorrhage, pulmonary haemorrhage/haemoptysis, abnormal hepatic function, intestinal perforation and ischaemic stroke.
The most common adverse reactions (experienced by at least 10% of the patients) of any grade in the RCC and STS trials included: diarrhoea, hair colour change, skin hypopigmentation, exfoliative rash, hypertension, nausea, headache, fatigue, anorexia, vomiting, dysgeusia, stomatitis, weight decreased, pain, elevated alanine aminotransferase and elevated aspartate aminotransferase.
Adverse drug reactions, all grades, which were reported in RCC and STS subjects or during the post-marketing period are listed below by MedDRA body system organ class, frequency and grade of severity. The following convention has been utilised for the classification of frequency: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); and not known (cannot be estimated from the available data).
12 Categories have been assigned based on absolute frequencies in the clinical trial data. Post-marketing data on safety and tolerability across all pazopanib clinical studies and from spontaneous reports have also been evaluated. Within each system organ class, adverse reactions with the same frequency are presented in order of decreasing seriousness.
03%) 1 0 Rare Thrombotic microangiopathy (including thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome)† not known not known not known Endocrine disorders Common Hypothyroidism 83 (7%) 1 (<1%) 0 Metabolism and nutrition disorders Very common Decreased appetitee 317 (28%) 14 (1%) 0 Common Hypophosphataemia 21 (2%) 7 (<1%) 0 Dehydration 16 (1%) 5 (<1%) 0 Uncommon Hypomagnesaemia 10 (<1%) 0 0 Not known Tumour lysis syndrome* not known not known not known Psychiatric disorders Common Insomnia 30 (3%) 0 0 13 Nervous system disorders Very common Dysgeusiac 254 (22%) 1 (<1%) 0 Headache 122 (11%) 11 (<1%) 0 Common Dizziness 55 (5%) 3 (<1%) 1 (<1%) Lethargy 30 (3%) 3 (<1%) 0 Paraesthesia 20 (2%) 2 (<1%) 0 Peripheral sensory neuropathy 17 (1%) 0 0 Uncommon Hypoaesthesia 8 (<1%) 0 0 Transient ischaemic attack 7 (<1%) 4 (<1%) 0 Somnolence 3 (<1%) 1 (<1%) 0 Cerebrovascular accident 2 (<1%) 1 (<1%) 1 (<1%) Ischaemic stroke 2 (<1%) 0 1 (<1%) Rare Posterior reversible encephalopathy / reversible posterior leukoencephalopathy syndrome† not known not known not known Eye disorders Common Vision blurred 19 (2%) 1 (<1%) 0 Uncommon Retinal detachment† 1 (<1%) 1 (<1%) 0 Retinal tear† 1 (<1%) 1 (<1%) 0 Eyelash discolouration 4 (<1%) 0 0 Cardiac disorders Uncommon Bradycardia 6 (<1%) 0 0 Myocardial infarction 5 (<1%) 1 (<1%) 4 (<1%) Cardiac dysfunctionf 4 (<1%) 1 (<1%) 0 Myocardial ischaemia 3 (<1%) 1 (<1%) 0 Vascular disorders Very common Hypertension 473 (41%) 115 (10%) 1 (<1%) Common Hot flush 16 (1%) 0 0 Venous thromboembolic event g 13 (1%) 6 (<1%) 7 (<1%) Flushing 12 (1%) 0 0 Uncommon Hypertensive crisis 6 (<1%) 0 2 (<1%) Haemorrhage 1 (<1%) 0 0 Rare Aneurysms and artery dissections† not known not known not known Respiratory, thoracic and mediastinal disorders Common Epistaxis 50 (4%) 1 (<1%) 0 Dysphonia 48 (4%) 0 0 Dyspnoea 42 (4%) 8 (<1%) 1 (<1%) Haemoptysis 15 (1%) 1 (<1%) 0 Uncommon Rhinorrhoea 8 (<1%) 0 0 Pulmonary haemorrhage 2 (<1%) 0 0 Pneumothorax 1 (<1%) 0 0 Rare Interstitial lung disease/pneumonitis† not known not known not known 14 Gastrointestinal disorders Very common Diarrhoea 614 (53%_) 65 (6%) 2 (<1%) Nausea 386 (34%) 14 (1%) 0 Vomiting 225 (20%) 18 (2%) 1 (<1%) Abdominal paina 139 (12%) 15 (1%) 0 Common Stomatitis 96 (8%) 4 (<1%) 0 Dyspepsia 83 (7%) 2 (<1%) 0 Flatulence 43 (4%) 0 0 Abdominal distension 36 (3%) 2 (<1%) 0 Mouth ulceration 28 (2%) 3 (<1%) 0 Dry mouth 27 (2%) 0 0 Uncommon Pancreatitis 8 (<1%) 4 (<1%) 0 Rectal haemorrhage 8 (<1%) 2 (<1%) 0 Haematochezia 6 (<1%) 0 0 Gastrointestinal haemorrhage 4 (<1%) 2 (<1%) 0 Melaena 4 (<1%) 1(<1%) 0 […]
EUOfficial regulatory label· Warnings and precautions· revised October 28, 2025[4]
Hepatic effects Cases of hepatic failure (including fatalities) have been reported during use of pazopanib. Administration of pazopanib to patients with mild or moderate hepatic impairment should be undertaken with caution and close monitoring.
5 x ULN regardless of the ALT value). 2). 2). Exposure at a 200 mg dose is markedly reduced, though highly variable, in these patients, with values considered insufficient to obtain a clinically relevant effect. 8). In the majority of the cases, isolated increases in ALT and AST have been reported, without concomitant elevations of alkaline phosphatase or bilirubin.
Patients over 60 years of age may be at greater risk for mild (>3 x ULN) to severe (>8 x ULN) elevation of ALT. Patients who carry the HLA-B*57:01 allele have an increased risk of pazopanib-associated ALT elevations. 1). Serum liver tests should be performed before initiation of treatment with pazopanib, at weeks 3, 5, 7 and 9, then at months 3 and 4, with additional tests as clinically indicated.
Periodic testing should then continue after month 4. 5 x ULN and AST and ALT 2 x ULN: Table 1 Dose modifications for drug-induced hepatotoxicity Liver test values Dose modification Transaminase elevation between 3 and 8 x ULN Continue on pazopanib with weekly monitoring of liver function until transaminases return to Grade 1 or baseline.
Transaminase elevation of >8 x ULN Interrupt pazopanib until transaminases return to Grade 1 or baseline. If the potential benefit of reinitiating pazopanib treatment is considered to outweigh the risk for hepatotoxicity, then reintroduce pazopanib at a reduced dose of 400 mg daily and perform serum liver tests weekly for 8 weeks.
Following reintroduction of pazopanib, if transaminase elevations >3 x ULN recur, then pazopanib should be permanently discontinued. Transaminase elevations >3 x ULN concurrently with bilirubin elevations >2 x ULN Permanently discontinue pazopanib.
Patients should be monitored until return to Grade 1 or baseline. Pazopanib is a UGT1A1 inhibitor. Mild, indirect (unconjugated) hyperbilirubinaemia may occur in patients with Gilbert’s syndrome. Patients with only a mild indirect hyperbilirubinaemia, known or suspected Gilbert’s syndrome, and elevation in ALT >3 x ULN should be managed as per the recommendations outlined for isolated ALT elevations.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
EUOfficial regulatory label· Contraindications· revised October 28, 2025[4]
1.
This is not medical advice. Consult a qualified healthcare professional.
5) and should be undertaken with caution and close monitoring. Hypertension In clinical studies with Pazopanib, events of hypertension including newly diagnosed symptomatic episodes of elevated blood pressure (hypertensive crisis) have occurred.
Blood pressure should be well controlled prior to initiating Pazopanib. Patients should be monitored for hypertension early after starting treatment (no longer than one week after starting Pazopanib) and frequently thereafter to ensure blood pressure control.
Elevated blood pressure levels (systolic blood pressure ≥150 mm Hg or diastolic blood pressure ≥100 mm Hg) occurred early in the course of treatment (appropriately 40% of cases occurred by day 9 and approximately 90% of cases occurred in the first 18 weeks).
8). Pazopanib should be discontinued if there is evidence of hypertensive crisis or if hypertension is severe and persists despite anti-hypertensive therapy and Pazopanib dose reduction. Posterior reversible encephalopathy syndrome (PRES)/Reversible posterior leukoencephalopathy syndrome (RPLS) PRES/RPLS has been reported in association with Pazopanib.
PRES/RPLS can present with headache, hypertension, seizure, lethargy, confusion, blindness and other visual and neurological disturbances, and can be fatal. Patients developing PRES/RPLS should permanently discontinue treatment with Pazopanib.
8). Patients should be monitored for pulmonary symptoms indicative of ILD/pneumonitis and Pazopanib should be discontinued in patients developing ILD or pneumonitis. Cardiac dysfunction/Heart failure The risks and benefits of Pazopanib should be considered before beginning therapy in patients who have pre-existing cardiac dysfunction.
The safety and pharmacokinetics of Pazopanib in patients with moderate to severe heart failure or those with a below normal left ventricular ejection fraction (LVEF) have not been studied. 8). In a randomised study comparing Pazopanib and sunitinib in RCC (VEG108844), subjects had baseline and follow up LVEF measurements.
Myocardial dysfunction occurred in 13% (47/362) of subjects in the Pazopanib arm compared to […]
42 PATIENT MEDICATION INFORMATION ................................................................................. 45 Votrient (pazopanib hydrochloride) […]
Monitor for signs and symptoms of gastrointestinal perforation or fistula. Withhold pazopanib tablets in case of Grade 2 or 3 gastrointestinal fistula and resume based on medical judgement. Permanently discontinue pazopanib tablets in case of gastrointestinal perforation or Grade 4 gastrointestinal fistula.
8 ) Interstitial Lung Disease/Pneumonitis: Can be fatal. Monitor patients for pulmonary symptoms. Permanently discontinue pazopanib tablets in patients who develop interstitial lung disease (ILD) or pneumonitis. 9 ) Posterior Reversible Encephalopathy Syndrome: Can be fatal.
Permanently discontinue pazopanib tablets in patients who develop posterior reversible encephalopathy syndrome (PRES). 10 ) Hypertension: Hypertension, including hypertensive crisis, has been observed. Do not initiate pazopanib tablets in patients with uncontrolled hypertension.
Optimize blood pressure prior to initiating pazopanib tablets. Monitor blood pressure as clinically indicated and initiate and adjust antihypertensive therapy as appropriate. Withhold and then dose reduce pazopanib tablets or permanently discontinue based on severity of hypertension.
11 ) Risk of lmpaired Wound Healing: Withhold pazopanib tablets for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of pazopanib tablets after resolution of wound healing complications has not been established.
12 ) Hypothyroidism: Monitor thyroid tests at baseline, during treatment and as clinically indicated and manage hypothyroidism as appropriate. 13 ) Proteinuria: Perform baseline and periodic urinalysis during treatment with follow up measurement of 24-hour urine protein as clinically indicated.
Withhold pazopanib tablets then resume at a reduced dose or permanently discontinue based on severity of proteinuria. Permanently discontinue in patients with nephrotic syndrome. 14 ) Tumor Lysis Syndrome: Cases of tumor lysis syndrome (TLS) (some fatal) have been reported in patients with RCC and STS.
Closely monitor patients at risk and treat as clinically indicated. 15 ) Infection: Serious infections (with or without neutropenia), some with fatal outcome, have been reported. Monitor for signs and symptoms of infection. Institute appropriate anti-infective therapy promptly.
Consider interruption or discontinuation of pazopanib tablets. 16 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and patients to use effective contraception.
1 Hepatic Toxicity Hepatotoxicity, manifested as increases in ALT, aspartate aminotransferase (AST) and bilirubin, occurred in patients who received pazopanib tablets. This hepatotoxicity can be severe and fatal. 5 )]. Transaminase elevations occur early in the course of treatment; 92% of all transaminase elevations of any grade occurred in the first 18 weeks.
In the randomized RCC trial (VEG105192), ALT > 3 x ULN occurred in 18% and ALT > 10 x ULN occurred in 4% of the 290 patients who received pazopanib tablets. Concurrent elevation in ALT > 3 x ULN and bilirubin > 2 x ULN in the absence of significant alkaline phosphatase > 3 x ULN occurred in 2%.
In the monotherapy trials, 2 patients died with disease progression and hepatic failure. In the randomized STS trial (VEG110727), ALT > 3 x ULN occurred in 18% and ALT > 8 x ULN occurred in 5% of the 240 patients who received pazopanib tablets.
Concurrent elevation in ALT > 3 x ULN and bilirubin > 2 x ULN in the absence of significant alkaline phosphatase > 3 x ULN occurred in 2%. One patient died of hepatic failure. Monitor liver tests 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 ALT returns to Grade 1 or baseline. 2 )]. Gilbert's Syndrome Pazopanib tablets is a uridine diphosphate (UDP)-glucuronosyl transferase 1A1 (UGT1A1) inhibitor. 5 )]. 2 )].
3 )]. Insufficient data are available to assess the risk of concomitant administration of alternative statins and pazopanib tablets. 2 QT Prolongation and Torsades de Pointes In the RCC trials, 558/586 patients were subject to routine electrocardiogram (ECG) monitoring and QT prolongation ≥ 500 msec was identified in 2% of these 558 patients.
In monotherapy trials, torsades de pointes occurred in < 1% of 977 patients who received pazopanib tablets. 4% (1/240) of patients, respectively, who received pazopanib tablets had post-baseline values between 500 to 549 msec. Post-baseline QT data were only collected in the STS trial if ECG abnormalities were reported as an adverse reaction.
5 )]. , calcium, magnesium, potassium) at baseline and as clinically indicated. Correct hypokalemia, hypomagnesemia, and hypocalcemia prior to initiating pazopanib tablets and during treatment. 3 Cardiac Dysfunction Cardiac dysfunction, including decreased left ventricular ejection fraction (LVEF) and congestive heart failure, occurred in patients who received pazopanib tablets.
6% of 586 patients without routine on-study LVEF monitoring. In the randomized RCC trial (VEG105192), myocardial dysfunction was defined as symptoms of cardiac dysfunction or ≥15% absolute decline in LVEF compared with baseline or a decline in LVEF of ≥10% compared with baseline that is also below the lower limit of normal.
In an RCC trial (COMPARZ), myocardial dysfunction occurred in 13% of the 362 patients on pazopanib tablets who had a baseline and post-baseline LVEF measurements. 5% of patients. In the randomized STS trial (VEG110727), myocardial dysfunction occurred in 11% of the 142 patients who had a baseline and a post-baseline LVEF measurements.
One percent (3/240) of patients who received pazopanib tablets had congestive heart failure, which did not resolve in one patient. , those with prior anthracycline therapy) possibly by increasing cardiac afterload. 11 )]. Monitor for clinical signs or symptoms of congestive heart failure.
Conduct baseline and periodic evaluation of LVEF in patients at risk of cardiac dysfunction, including previous anthracycline exposure. 2 )]. 9% of 586 patients, and cerebral/intracranial hemorrhage was observed in < 1% (2/586) of patients treated with pazopanib tablets.
In the randomized RCC trial (VEG105192), 13% of 290 patients treated with pazopanib tablets experienced at least 1 hemorrhagic event. The most common hemorrhagic events were hematuria (4%), epistaxis (2%), hemoptysis (2%), and rectal hemorrhage (1%).
Nine of 37 patients treated with pazopanib tablets who had hemorrhagic events experienced serious events, including pulmonary, gastrointestinal, and genitourinary hemorrhage. One percent of patients treated with pazopanib tablets died from hemorrhage.
In the randomized STS trial (VEG110727), 22% of 240 patients treated with pazopanib tablets experienced at least 1 hemorrhagic event. The most common hemorrhagic events were epistaxis (8%), mouth hemorrhage (3%), and anal hemorrhage (2%).
Grade 4 hemorrhagic events occurred in 1% of patients and included intracranial hemorrhage, subarachnoid hemorrhage, and peritoneal hemorrhage. Pazopanib tablets has not been studied in patients who have a history of hemoptysis, cerebral hemorrhage, or clinically significant gastrointestinal hemorrhage in the past 6 months.
2 )]. 3% of 586 patients. 3% had a cerebrovascular accident, and 1% had an event of transient ischemic attack. 4% had a cerebrovascular accident. Pazopanib tablets has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months.
2 )]. 6 Venous Thromboembolic Events Venous thromboembolic events (VTEs), including venous thrombosis and fatal pulmonary embolus (PE), occurred in patients who received pazopanib tablets. In the randomized RCC trial (VEG105192), VTEs occurred in 1% of 290 patients who received pazopanib tablets.
In the randomized STS trial (VEG110727), VTEs were reported in 5% of 240 patients who received pazopanib tablets. Fatal PE occurred in 1% (2/240). Monitor for signs and symptoms of VTE and PE. 2 )]. 7 Thrombotic Microangiopathy Thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), occurred in clinical trials of pazopanib tablets as monotherapy, in combination with bevacizumab, and in combination with topotecan.
Pazopanib tablets is not indicated for use in combination with other agents. Six of the 7 TMA cases occurred within 90 days of the initiation of pazopanib tablets. Improvement of TMA was observed after treatment was discontinued. Monitor for signs and symptoms of TMA.
Permanently discontinue pazopanib tablets in patients developing TMA. Manage as clinically indicated. 9% of 586 patients and 1% of 382 patients who received pazopanib tablets, respectively. 3% (1/382) of these patients in the STS trials.
Monitor for signs and symptoms of gastrointestinal perforation or fistula. Withhold pazopanib tablets in case of Grade 2 or 3 gastrointestinal fistula and resume based on medical judgement. 2 )]. 9 Interstitial Lung Disease/Pneumonitis Interstitial lung disease (ILD)/pneumonitis, which can be fatal, has been reported with pazopanib tablets across clinical trials.
1% of patients treated with pazopanib tablets. Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis. 2 )]. 10 Posterior Reversible Encephalopathy Syndrome Posterior Reversible Encephalopathy Syndrome (PRES) has been reported in patients who received pazopanib tablets and may be fatal.
PRES is a neurological disorder which can present with headache, seizure, lethargy, confusion, blindness, and other visual and neurologic disturbances. Mild to severe hypertension may be present. Confirm diagnosis of PRES by magnetic resonance imaging.
Permanently discontinue pazopanib tablets in patients who develop PRES. 11 Hypertension Hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg) and hypertensive crisis were observed in patients treated with pazopanib tablets.
1 )]. About 40% of cases occurred by Day 9 and about 90% of cases occurred in the first 18 weeks across clinical trials. Approximately 1% of patients required permanent discontinuation of pazopanib tablets because of hypertension. Do not initiate pazopanib tablets in patients with uncontrolled hypertension.
Optimize blood pressure prior to initiating pazopanib tablets. Monitor blood pressure as clinically indicated and initiate and adjust antihypertensive therapy as appropriate. 2 )]. 12 Risk of Impaired Wound Healing Impaired wound healing complications can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway.
Therefore, pazopanib tablets has the potential to adversely affect wound healing. Withhold pazopanib tablets at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing.
The safety of resumption of pazopanib tablets after resolution of wound healing complications has not been established. 13 Hypothyroidism Hypothyroidism, confirmed based on a simultaneous rise of TSH and decline of T4, occurred in 7% of 290 patients who received pazopanib tablets in the randomized RCC trial (VEG105192) and in 5% of 240 patients who received pazopanib tablets in the randomized STS trial (VEG110727).
Hypothyroidism occurred in 4% of the 586 patients in the RCC trials and 5% of the 382 patients in the STS trials. Monitor thyroid tests at baseline, during treatment and as clinically indicated and manage hypothyroidism as appropriate.
14 Proteinuria In the randomized RCC trial (VEG105192), proteinuria occurred in 9% of 290 patients who received pazopanib tablets. In 2 patients, proteinuria led to discontinuation of pazopanib tablets. In the randomized STS trial (VEG110727), proteinuria occurred in 1% of 240 patients and nephrotic syndrome occurred in 1 patient.
Treatment was discontinued in the patient with nephrotic syndrome. Perform baseline and periodic urinalysis during treatment with follow up measurement of 24-hour urine protein as clinically indicated. Withhold pazopanib tablets then resume at a reduced dose or permanently discontinue based on severity of proteinuria.
2 )]. 2 )]. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis, and treat as clinically indicated.
16 Infection Serious infections (with or without neutropenia), including some with fatal outcome, have been reported. Monitor patients for signs and symptoms of infection. Institute appropriate anti-infective therapy promptly and consider interruption or discontinuation of pazopanib tablets for serious infections.
17 Increased Toxicity With Other Cancer Therapy Pazopanib tablets is not indicated for use in combination with other agents. Clinical trials of pazopanib tablets in combination with pemetrexed and lapatinib were terminated early due to increased toxicity and mortality.
The fatal toxicities observed included pulmonary hemorrhage, gastrointestinal hemorrhage, and sudden death. A safe and effective combination dose has not been established with these regimens. 18 Increased Toxicity in Developing Organs The safety and effectiveness of pazopanib tablets in pediatric patients have not been established.
Pazopanib tablets are not indicated for use in pediatric patients. 4 )]. 19 Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, pazopanib tablets can cause fetal harm when administered to a pregnant woman.
Administration of pazopanib to pregnant rats and rabbits during the period of organogenesis resulted in maternal toxicity, teratogenicity, and abortion at systemic exposures lower than that observed at the maximum recommended human dose (MRHD) of 800 mg (based on area under the curve [AUC]).
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with pazopanib tablets and for at least 2 weeks following the final dose. 3 )].
5) and should be undertaken with caution and close monitoring. Hypertension In clinical studies with pazopanib, events of hypertension including newly diagnosed symptomatic episodes of elevated blood pressure (hypertensive crisis) have occurred.
Blood pressure should be well controlled prior to initiating pazopanib. Patients should be monitored for hypertension early after starting treatment (no longer than one week after starting pazopanib) and frequently thereafter to ensure blood pressure control.
Elevated blood pressure levels (systolic blood pressure ≥150 mm Hg or diastolic blood pressure ≥100 mm Hg) occurred early in the course of treatment (approximately 40% of cases occurred by day 9 and approximately 90% of cases occurred in the first 18 weeks).
8). Pazopanib should be discontinued if there is evidence of hypertensive crisis or if hypertension is severe and persists despite anti-hypertensive therapy and pazopanib dose reduction. Posterior reversible encephalopathy syndrome (PRES)/Reversible posterior leukoencephalopathy syndrome (RPLS) PRES/RPLS has been reported in association with pazopanib.
PRES/RPLS can present with headache, hypertension, seizure, lethargy, confusion, blindness and other visual and neurological disturbances, and can be fatal. Patients developing PRES/RPLS should permanently discontinue treatment with pazopanib.
8). Patients should be monitored for pulmonary symptoms indicative of ILD/pneumonitis and pazopanib should be discontinued in patients developing ILD or pneumonitis. Cardiac dysfunction/Heart failure The risks and benefits of pazopanib should be considered before beginning therapy in patients who have pre-existing cardiac dysfunction.
The safety and pharmacokinetics of pazopanib in patients with moderate to severe heart failure or those with a below normal left ventricular ejection fraction (LVEF) have not been studied. 8). In a randomised study comparing pazopanib and sunitinib in RCC (VEG108844), subjects had baseline and follow up LVEF measurements.
Myocardial dysfunction occurred in 13% (47/362) of subjects in the pazopanib arm compared to […]