- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Tablets containing pazopanib
Advanced renal cell carcinoma
Sarcoma - soft tissue
First line treatment of advanced Renal Cell Carcinoma and for patients who have received prior cytokine therapy for advanced disease.
Treatment of 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.
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
The recommended dose is 800 mg pazopanib once a day.
Dose modification should be done in 200 mg steps based on individual tolerability in order to manage adverse reactions. Dose should not exceed 800 mg.
Patients with Renal Impairment
Caution is advised in patients with creatinine clearance below 30 ml/minute.
Patients with Hepatic Impairment
Normal bilirubin and any degree of raised alanine transferase (ALT): 800 mg pazopanib once daily.
Elevation of bilirubin (greater than 35% direct) up to 1.5 times upper limit of normal (ULN) regardless of ALT values: 800 mg pazopanib once daily.
Elevation of bilirubin greater than 1.5 times to 3 times ULN regardless of ALT values: 200 mg pazopanib once daily.
Additional Dosage Information
Dose modifications for drug induced hepatotoxicity
Transaminase elevation between 3 and 8 times upper limit of normal (ULN)
Continue treatment monitoring liver function weekly until transaminases return to grade 1 or baseline.
Transaminase elevation greater than 8 times ULN
Interrupt treatment until transaminases return to grade 1 or baseline. If the benefit of reinitiating pazopanib outweighs the risk of hepatotoxicity, reintroduce pazopanib at 400 mg once a day. Monitor liver function weekly for 8 weeks. If transaminase elevations are greater than 3 times ULN after reintroduction then permanently discontinue treatment.
Transaminase elevation greater than 3 times ULN with bilirubin elevations greater than 2 times ULN
Permanently discontinue treatment. Monitor patients until levels return to grade 1 or baseline.
Patients with only a mild indirect hyperbilirubinaemia, known or suspected Gilbert's syndrome and transaminase elevation greater than 3 times ULN should be managed as outlined for isolated transaminase elevations.
Children under 18 years
Within 6 months of haemoptysis
Serum bilirubin above 3 times upper limit of normal
Within 6 months of cerebrovascular haemorrhage
Within 6 months of severe gastrointestinal haemorrhage
Precautions and Warnings
Family history of long QT syndrome
History of treatment with anthracyclines
Predisposition to gastrointestinal perforation
Predisposition to venous thromboembolism
Risk factors for cardiovascular disorder
Risk of cerebrovascular accident
Risk of haemorrhage
Giant cell arteritis
History of aneurysm
History of torsade de pointes
Ischaemic heart disease
Long QT syndrome
Mild hepatic impairment
Occlusive peripheral arterial disease
Renal impairment - creatinine clearance below 30 ml/minute
Serum bilirubin between 1.5 and 3 times upper limit of normal
Vascular Ehlers-Danlos syndrome
Dose adjustment may be necessary in patients with hepatic impairment
Advise ability to drive/operate machinery may be affected by side effects
Consider premedication with hypouricaemic agent
Ensure hypertension is controlled prior to treatment
Maintain adequate hydration of patient prior / during treatment
Treatment to be prescribed under the supervision of a specialist
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Measurement of LV ejection fraction recommended before and during treatment
Monitor hepatic function at months 3 and 4, and periodically thereafter
Monitor hepatic function on weeks 3, 5, 7, and 9
Monitor hepatic function prior to treatment
Monitor liver function weekly if isolated transaminase elevation up to 8ULN
Monitor blood pressure regularly
Monitor ECG in patients at risk of QT prolongation
Monitor for signs and symptoms of interstitial lung disease
Monitor for signs and symptoms of pneumonitis
Monitor for signs/symptoms of pneumothorax
Monitor patients for signs and symptoms of cardiac failure
Monitor patients for signs of tumour lysis syndrome
Monitor serum electrolytes
Monitor thyroid function regularly
Perform regular urinalysis
Advise patient to report any new or worsening respiratory symptoms
Advise patient to report headaches, seizures, confusion, visual disturbance
Reduce dose if hypertension cannot be controlled
Discontinue at least 7 days prior to scheduled surgery
Discontinue at first signs of thrombotic microangiopathy
Discontinue if AST or ALT level > 3x ULN and bilirubin > 2x ULN
Discontinue if evidence of interstitial lung disease
Discontinue if Grade 4 proteinuria occurs (Nephrotic syndrome)
Discontinue if persistent hypertension unresponsive to therapy occurs
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue if treatment related pneumonitis is diagnosed
Discontinue in patients with wound dehiscence
Interrupt treatment if hepatic transaminases > 8 times ULN
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level
Female: Contraception required during and for 2 weeks after treatment
Male: Use of condoms required during and for 2 weeks after treatment
Advise patient on giving up smoking
If persistent hypertension occurs despite treatment, pazopanib dose should be reduced. Suspension of pazopanib is recommended in patients with persistently elevated blood pressure values (greater than 140/90 mmHg) or persistent severe arterial hypertension despite anti-hypertensive treatment and dose reduction of pazopanib.
Posterior reversible encephalopathy syndrome (PRES) has been reported in some patients treated with this agent. If patients present with symptoms indicating PRES such as headache, altered mental state, seizures and visual disturbances, an MRI should be performed. If PRES is diagnosed, treatment should be discontinued and adequate blood pressure and seizure control administration is advisable. The safety of reinstating treatment in patients previously experiencing PRES is unknown.
Neutropenia, thrombocytopenia and palmar-plantar erythrodysesthesia syndrome were observed more frequently in patients of east Asian descent.
Risk factors for aneurysm and artery dissection
Use of systemic VEGF inhibitors may promote the formation of aneurysms or artery dissections, mainly in relation to aortic aneurysm rupture and aortic dissection. It is therefore important to consider the risk of aneurysm and artery dissection in patients with risk factors such as hypertension, history of aneurysm, smoking, diabetes, coronary, cerebrovascular or peripheral arterial disease, and hyperlipidaemia. Other risk factors include Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, and the use of fluoroquinolones. In patients receiving VEGF inhibitors, any modifiable risk factors such as smoking and hypertension should be reduced as far as possible.
Pregnancy and Lactation
Use in pregnancy is contraindicated.
Studies in rats and rabbits have shown pazopanib to be embryotoxic and teratogenic but the risk to humans is unknown. However as renal carcinoma is a fatal condition, treatment should not be withheld due to pregnancy as long as informed consent is obtained.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Breastfeeding is contraindicated during treatment with pazopanib.
There is limited data on the excretion of pazopanib in human or animal milk therefore a risk to the nursing infant cannot be excluded. The molecular weight (about 438 for the free base) and long elimination half life (about 31 hours), suggest that the drug will be excreted into breast milk, but the high plasma protein binding (greater than 99%) might limit the amount (Brigs 2011).
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
To be taken orally and the tablets must be swallowed whole with water at least 1 hour before or 2 hours after a meal.
Advise patients to avoid grapefruit products whilst on pazopanib.
Advise patients against taking concurrent St John's Wort.
Advise patients to report headache, seizures, confusion and visual disturbances promptly.
Advise women of child bearing potential to use adequate contraception during and for 2 weeks after treatment.
Advise patients that side effect such as dizziness, tiredness or weakness may affect their ability to drive or operate machinery.
Blood urea increased
Changes in hair colour
Decreased blood glucose
Elevated amylase levels
Elevated serum lipase
Gamma glutamyl transferase (GGT) increased
Increase in serum ALT/AST
Interstitial lung disease
Mucous membrane disorder
Palmar-Plantar Erythrodysaesthesia syndrome
Possible alteration of thyroid function tests
Posterior reversible encephalopathy syndrome (PRES)
Prolongation of QT interval
Serum bilirubin increased
Serum creatinine increased
Transient ischaemic attack
Tumour lysis syndrome
Urinary tract bleeding
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Last Full Review Date: November 2013
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press. Accessed on 18 June 2015.
MHRA Drug Safety Update July 2020
Available at: https://www.gov.uk/drug-safety-update/systemically-administered-vegf-pathway-inhibitors-risk-of-aneurysm-and-artery-dissection
Last accessed: 10 November 2020
Summary of Product Characteristics: Votrient 200 mg and 400 mg film coated tablets. Novartis UK Ltd. Revised July 2020.
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Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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