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Pharmacologic class: Selective multi-targeted tyrosine kinase inhibitor
Therapeutic class: Antineoplastic
Pregnancy risk category D
FDA Box Warning
• Severe and fatal hepatotoxicity has been observed in clinical studies.
• Monitor hepatic function and interrupt, reduce, or discontinue dosing as recommended.
Specifically targets growth factor receptors associated with angiogenesis and tumor-cell proliferation; also exhibits inhibition of vascular endothelial growth factor receptors, platelet-derived growth factor receptors, fibroblast growth factor receptors, stem cell factor receptor (c-Kit), inter-leukin-2 receptor inducible T-cell kinase, leukocyte-specific protein tyro-sine kinase, and transmembrane glycoprotein receptor tyrosine kinase
Tablets: 200 mg
⊘Indications and dosages
➣ Advanced renal cell carcinoma (RCC); advanced soft-tissue sarcoma (STS) in patients who have received prior chemotherapy
Adults: 800 mg P.O. daily. In RCC, initial dosage reduction should be 400 mg, and additional dosage decrease or increase should be in 200-mg steps based on individual tolerability. In STS, a decrease or increase should be in 200-mg steps based on individual tolerability.
• Moderate hepatic impairment
• Strong CYP3A4 inducers/inhibitors
Use cautiously in:
• severe hepatic impairment with total bilirubin greater than three times the upper limit of normal (ULN)
• mild to moderate hepatic impairment, proteinuria
• hypothyroidism, hypertension, cardiac disease, patients at risk for developing QT-interval prolongation
• signs and symptoms of serious infection
• patients at increased risk for myocardial infarction (MI), angina, ischemic stroke, transient ischemic attack, and GI perforation or fistula
• hemoptysis; cerebral or clinically significant GI hemorrhage in past 6 months (avoid use)
• patients undergoing surgical procedures
• concurrent use of other cancer therapies (not indicated)
• concurrent use of antiarrhythmics and other drugs that may prolong QT interval
• concurrent use of strong CYP3A4 inducers or inhibitors (avoid use)
• concurrent use of CYP substrates (use not recommended)
• concurrent use of simvastatin
• elderly patients
• pregnant or breastfeeding patients
• children (safety and efficacy not established).
• Administer without food at least 1 hour before or 2 hours after a meal. Don't give with grapefruit or grapefruit juice. Don't crush tablets.
• Perform baseline ECG and LVEF evaluation, and maintain electrolytes within normal range during therapy.
☞ Perform baseline urinalysis and discontinue drug for Grade 4 proteinuria.
• Ensure patient's blood pressure is well controlled before starting drug.
☞ Before starting treatment, monitor hepatic function and interrupt, reduce, or discontinue dosing as recommended.
☞ Don't administer to patient who has had MI, angina, ischemic stroke, transient ischemic attack, hemoptysis, or clinically significant GI hemorrhage in previous 6 months.
☞ Be aware that serious infections, including some with fatal outcome, have been reported. Institute appropriate anti-infective therapy promptly and consider drug interruption or discontinuation for serious infections.
☞ Temporarily interrupt therapy in patients undergoing surgical procedures for at least 7 days before surgery. Discontinue drug in patients who develop wound dehiscence.
☞ Be aware that drug isn't indicated for use in combination with other cancer agents, because of possible increased toxicity and mortality (pulmonary hemorrhage, GI hemorrhage, and sudden death).
CNS: fatigue, asthenia, headache
CV: hypertension, decreased ejection
fraction, congestive heart failure (CHF), QT-interval prolongation, torsades de pointes
GI: nausea, vomiting, diarrhea, anorexia, dyspepsia, GI perforation and fistula
Hematologic: leukopenia, neutropenia, thrombocytopenia, lymphocytopenia, arterial and venous thrombotic events, hemorrhagic events
Hepatic: abnormal liver function test values, hepatotoxicity
Metabolic: altered electrolyte levels, hypothyroidism
Musculoskeletal: musculoskeletal pain
Skin: alopecia, rash, skin depigmentation, impaired wound healing, palmar-plantar erythrodysesthesia
Other: hair color changes, chest pain, dysgeusia, facial edema, weight loss, decreased appetite, infection, tumor pain, reversible posterior leukoencephalopathy syndrome
Drug-drug.CYP3A4 substrates (such as dextromethorphan, midazolam, paclitaxel): inhibited metabolism of these drugs
Simvastatin: increased risk of ALT elevations
Strong CYP3A4 inducers (such as rifampin): decreased pazopanib concentration
Strong CYP3A4 inhibitors (such as clarithromycin, ketoconazole, ritonavir): increased pazopanib concentration
Drug-diagnostic tests.ALT, AST, total
bilirubin: increased levels
Glucose: increased or decreased level Hemoglobin, magnesium, neutrophils, phosphorus, platelets, sodium: decreased levels
Drug-food.Any food: increased pazopanib systemic exposure
Grapefruit juice: inhibited CYP3A4 activity and increased pazopanib plasma concentration
• Monitor CBC with differential closely.
☞ Periodically monitor urinalysis during treatment, with follow-up measurement of 24-hour urine protein as clinically indicated. Interrupt therapy and reduce dosage for 24-hour urine protein of 3 g or more; discontinue drug for repeat episodes despite dosage reductions.
☞ Monitor serum liver function tests at least once every 4 weeks for at least first 4 months of treatment or as clinically indicated; continue periodic monitoring thereafter. If ALT levels of more than three times ULN occur concurrently with bilirubin levels of more than two times ULN, permanently discontinue drug.
☞ Closely monitor patient for QT-interval prolongation and signs or symptoms of CHF; periodically monitor ECG and maintain electrolyte levels within normal range.
• Periodically evaluate left ventricular ejection fraction in patients at risk for cardiac dysfunction, including patients who have received previous anthracycline exposure.
• Monitor patients for hypertension; treat as needed. If hypertension persists despite therapy, reduce dosage or discontinue drug as appropriate.
☞ Closely monitor patient for signs and symptoms of reversible posterior leukoencephalopathy syndrome (RPLS) (headache, seizure, lethargy, confusion, blindness, other visual and neurologic disturbances, and possibly mild to severe hypertension). Discontinue drug if RPLS develops.
☞ Closely monitor patient for signs and symptoms of infection, hemorrhage, thrombotic events, and GI perforation or fistula.
• Be aware that proactive thyroid function monitoring is recommended.
• Monitor patient for impaired wound healing after surgery.
• Closely watch for ALT elevations in patients also taking simvastatin.
• Tell patient to take drug without food at least 1 hour before or 2 hours after a meal, not to crush tablets, and to avoid grapefruit and grapefruit juice.
☞ Instruct patient to immediately report unusual tiredness; dizziness; numbness or weakness on one side of the body; trouble talking; shortness of breath; irregular heartbeats; high blood pressure; chest pain; bleeding; itching; yellowing of skin or eyes; dark urine; right upper abdominal pain, discomfort, or distention; wounds that don't heal; or red, painful hands and feet.
• Teach patient how to manage diarrhea and to notify prescriber if moderate to severe diarrhea occurs.
• Tell patient that drug may cause depigmentation of the hair or skin.
• Instruct patient to tell prescriber about all drugs he's taking, because some drugs have potential for serious drug interactions and shouldn't be taken with pazopanib.
• Advise female patient of childbearing age to avoid pregnancy during therapy.
• Advise breastfeeding patient that she should decide whether to discontinue breastfeeding or discontinue drug, taking into account importance of drug for her treatment.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and food mentioned above.
Pharmacologic: kinase inhibitors
Time/action profile (blood levels)
|PO||PO||2–4 hr||24 hr|
Adverse Reactions/Side Effects
Central nervous system
- reversible posterior leukoencephalopathy syndrome (life-threatening)
- stroke (life-threatening)
- fatigue (most frequent)
- weakness (most frequent)
- myocardial infarction (life-threatening)
- qt interval prolongation (life-threatening)
- deep vein thrombosis (life-threatening)
- bradycardia (most frequent)
- hypertension (most frequent)
- altered taste
- chest pain
- heart failure
- gi perforation/fistula (life-threatening)
- hepatotoxicity (life-threatening)
- pancreatitis (life-threatening)
- abdominal pain (most frequent)
- anorexia (most frequent)
- diarrhea (most frequent)
- nausea (most frequent)
- vomiting (most frequent)
- hemolytic uremic syndrome (life-threatening)
- facial edema
- palmar-plantar erythrodysesthesia (hand-foot syndrome)
- skin depigmentation
- bleeding (life-threatening)
- thromboembolic events (life-threatening)
- thrombotic thrombocytopenic purpura (life-threatening)
- ↑ lipase
- weight loss
- pulmonary embolism (life-threatening)
- hair color changes (depigmentation) (most frequent)
Drug-Drug interactionConcurrent use of strong CYP3A4 inhibitors, including ketoconazole, ritonavir and clarithromycin may ↑ levels and should be avoided; if required, dose of pazopanib should be ↓ to 400 mg daily or more if necessary.Concurrent use of strong CYP3A4 inducers, including rifampin, may ↓ levels and effectiveness and should be avoided.Concurrent use with drugs with narrow therapeutic windows that are metabolized by CYP3A4, CYP2D6, or CYP2C8 may ↑ levels of such drugs and the risk of toxicity/adverse reactions is not recommended.↑ risk of hepatotoxicity with simvastatin Grapefruit juice may ↑ levels; avoid concurrent use.
Hepatic ImpairmentOral (Adults) Moderate hepatic impairment—200 mg once daily.
- Monitor BP during frequent therapy; may cause hypertension. BP should be well-controlled prior to initiating therapy. If persistent hypertension occurs despite antihypertensive therapy, reduce dose. If hypertension persists and is severe, discontinue therapy. Baseline and periodic evaluation of LVEF is recommended in patients at risk of cardiac dysfunction.
- Obtain baseline ECG and monitor periodically during therapy. Maintain serum calcium, magnesium, and potassium within normal range during therapy.
- Monitor for signs and symptoms of GI perforation and fistula (abdominal pain; swelling in stomach area; vomiting blood; black sticky stools; GI bleeding) during therapy.
- Lab Test Considerations: Monitor serum liver tests before initiation and wks 3, 5, 7, and 9, then at month 3 and month 4 if symptoms occur. Monitor periodically after month 4. If isolated ALT ↑ between 3 and 8 times the upper limit of normal, therapy may continue with weekly monitoring of liver function until ALT returns to Grade 1 or baseline. If isolated ALT ↑ >8 times the upper limit of normal, stop therapy until ALT returns to Grade 1 or baseline. If benefit outweighs risk, may reintroduce at reduced dose of 400 mg/day with weekly serum liver tests for 8 wk. Following reintroduction, if ALT ↑ >3 times the upper limit of normal recurs, permanently discontinue pazopanib. If ALT ↑ occurs concurrently with ↑ serum bilirubin >2 times the upper limit of normal, discontinue pazopanib permanently. Monitor liver function tests until return to baseline. Patients with only mild indirect hyperbilirubinemia (Gilbert's syndrome) and ↑ ALT >3 times the upper limit of normal should be managed as per recommendations for ↑ ALT.
- Monitor thyroid function periodically during therapy. May cause hypothyroidism.
- Obtain baseline urinalysis and monitor periodically. May cause proteinuria. Discontinue therapy if Grade 4 proteinuria develops.
- May cause leukopenia, neutropenia, thrombocytopenia, and lymphocytopenia.
- May cause ↑AST and ↓ serum phosphorous, sodium, and magnesium. May cause ↑ or ↓ serum glucose.
Potential Nursing DiagnosesDeficient knowledge, related to medication regimen (Patient/Family Teaching)
- Oral: Administer at least 1 hr before or 2 hr after a meal. Swallow tablets whole; do not crush tablets.
- Instruct patient to take pazopanib on an empty stomach as directed. Take missed doses as soon as remembered; if less than 12 hr before next dose, omit dose. Advise patient to read the Medication Guide prior to taking pazopanib and with each Rx refill; new information may be available.
- Advise patient to avoid drinking grapefruit juice or eating grapefruit during therapy; may increase amounts of panopanib absorbed.
- Advise patient to notify health care professional immediately if signs and symptoms of liver problems (yellowing of skin or whites of eyes, unusual darkening of urine, unusual tiredness, pain in the right upper stomach area), heart failure (shortness of breath), heart attack or stroke (chest pain or pressure; pain in arms, back, neck or jaw; shortness of breath; numbness or weakness on one side of body; trouble talking; headache; dizziness), blood clots (new chest pain, trouble breathing or shortness of breath that starts suddenly; leg pain; swelling of arms and hands, or legs and feet; cool or pale arm or leg), bleeding problems (unusual bleeding, bruising, wounds that do not heal), GI perforation or fistula, reversible posterior leukoencephalopathy syndrome (headaches, seizures, lack of energy, confusion, high blood pressure, loss of speech, blindness or changes in vision, and problems thinking), severe increase in blood pressure (severe chest pain, severe head ache, blurred vision, confusion, nausea and vomiting, severe anxiety, shortness of breath, seizures, unconsciousness) or severe infections (fever; cold symptoms such as runny nose or sore throat that do not go away; flu symptoms such as cough, tiredness, and body aches; pain when urinating; cuts, scrapes or wounds that are red, warm, swollen or painful) occur.
- Inform patient that diarrhea frequently occurs. Instruct patient on ways to manage diarrhea and to notify health care professional if moderate to severe diarrhea occurs.
- Inform patient that loss of color (depigmentation) of skin or hair may occur during therapy. Explore methods of coping.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
- Advise patient to notify health care professional of any impending surgery. Panzopanib must be stopped for at least 7 days prior to surgery due to the affects on healing.
- Advise female patients to use effective contraception during therapy and to notify health care professional immediately if pregnancy is suspected.
- Decreased growth and spread of renal cell carcinoma.
- Improvement in spread of sarcoma.