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VOTRIENT is a brand name for Pazopanib, supplied as a tablet. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 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…
Verbatim from this product's HC label. Tap a section to expand.
, 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
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.
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 .....................................................................
4 1 INDICATIONS .............................................................................................................. 1 Pediatrics ..........................................................................................................
2 Geriatrics........................................................................................................... 5 2 CONTRAINDICATIONS .................................................................................................
5 3 SERIOUS WARNINGS AND PRECAUTIONS BOX ............................................................ 5 4 DOSAGE AND ADMINISTRATION................................................................................. 1 Dosing Considerations .......................................................................................
2 Recommended Dose and Dosage Adjustment..................................................... 4 Administration................................................................................................... 5 Missed Dose ......................................................................................................
6 5 OVERDOSAGE ............................................................................................................. 7 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ................................. 7 7 WARNINGS AND PRECAUTIONS ..................................................................................
). 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).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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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.
Votrient (pazopanib hydrochloride) Product Monograph Page 18 of 54 Soft Tissue Sarcoma Error! 3 presents the most common adverse reactions occurring in ≥ 10 % of patients who received VOTRIENT in the pivotal STS study. Table 3 Adverse Reactions Occurring in 10% of patients with STS who Received VOTRIENT (study VEG110727) VOTRIENT Placebo (N = 240) (N = 123) All Gradesa Grade 3 Grade 4 All Gradesa Grade 3 Grade 4 Adverse Reactions % % % % % % Fatigue 65 13 <1 48 4 <1 Diarrhea 59 5 0 15 <1 0 Nausea 56 3 0 22 2 0 Weight decreased 48 4 0 15 0 0 Hypertension 42 7 0 6 0 0 Appetite decreased 40 6 0 19 0 0 Hair color changes 39 0 0 2 0 0 Vomiting 33 3 0 11 <1 0 Tumour pain 29 8 0 21 7 2 Dysgeusia 28 0 0 3 0 0 Headache 23 <1 0 8 0 0 Musculoskeletal pain 23 2 0 20 2 0 Myalgia 23 2 0 9 0 0 Gastrointestinal pain 23 3 0 9 4 0 Dyspnea 20 5 <1 17 5 <1 Exfoliative rash 18 <1 0 9 0 0 Cough 17 <1 0 12 <1 0 Peripheral edema 14 2 0 9 2 0 Alopecia 12 0 0 <1 0 0 Dizziness 11 <1 0 4 0 0 Skin disorderb 11 2 0 <1 0 0 Skin hypopigmentation 11 0 0 0 0 0 Stomatitis 11 <1 0 3 0 0 Chest pain 10 2 0 6 0 0 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. 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 […]
1 Special Populations .......................................................................................... 1 Pregnant Women ....................................................................................... 2 Breast-feeding............................................................................................
3 Pediatrics ................................................................................................... 4 Geriatrics ................................................................................................... 16 8 ADVERSE REACTIONS ................................................................................................
1 Adverse Reaction Overview.............................................................................. 2 Clinical Trial Adverse Reactions ........................................................................ 3 Less Common Clinical Trial Adverse Reactions ..................................................
4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data ...................................................................................................... 5 Post-Market Adverse Reactions........................................................................
22 9 DRUG INTERACTIONS................................................................................................ 2 Drug Interactions Overview.............................................................................. 4 Drug-Drug Interactions ....................................................................................
5 Drug-Food Interactions .................................................................................... 6 Drug-Herb Interactions .................................................................................... 7 Drug-Laboratory Test Interactions ....................................................................
30 10 CLINICAL PHARMACOLOGY ....................................................................................... 1 Mechanism of Action.................................................................................. 2 Pharmacodynamics ....................................................................................
3 Pharmacokinetics....................................................................................... 31 11 STORAGE, STABILITY AND DISPOSAL ......................................................................... 32 12 SPECIAL HANDLING INSTRUCTIONS...........................................................................
32 PART II: SCIENTIFIC INFORMATION ...................................................................................... 33 13 PHARMACEUTICAL INFORMATION............................................................................ 33 14 CLINICAL TRIALS........................................................................................................
1 Clinical Trials by Indication.......................................................................... 34 Metastatic Renal Cell Carcinoma................................................................................ 34 Soft Tissue Sarcoma ..................................................................................................
38 15 MICROBIOLOGY ........................................................................................................ 42 16 NON-CLINICAL TOXICOLOGY .....................................................................................
42 PATIENT MEDICATION INFORMATION ................................................................................. 45 Votrient (pazopanib hydrochloride) […]