Pazopanib

Pazopanib is a prescription medicine used for the treatment of advanced renal cell carcinoma and soft tissue sarcomas.

• Pazopanib is available under the following different brand names: Votrient

Adult dosage

Tablet

• 200mg
• 400mg

Advanced Renal Cell Carcinoma

Adult dosage

• 800 mg orally every day on empty stomach (at least 1 hr before meals or 2 hours after meals)

Soft Tissue Sarcomas

Adult dosage

• 800 mg orally every day on empty stomach (at least 1 hr before meals or 2 hours after meals)

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of the Pazopanib include:

• nausea,
• vomiting,
• diarrhea,
• stomach pain,
• loss of appetite,
• weight loss,
• trouble breathing,
• tumor pain,
• bone pain,
• muscle pain,
• headache,
• feeling tired,
• changes in hair color, and
• changes in the sense of taste.

Serious side effects of the Pazopanib include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• unusual bleeding or bruising,
• slow healing of a wound or surgical incision,
• any wound that will not heal,
• sudden chest pain or discomfort,
• wheezing,
• dry cough,
• headache,
• confusion,
• change in mental status,
• vision loss,
• seizure,
• sudden numbness or weakness,
• severe headache,
• slurred speech,
• vision problems,
• chest pain,
• sudden shortness of breath,
• pain or cold feeling in an arm or leg,
• chest pain or pressure,
• pain spreading to the jaw or shoulder,
• nausea,
• sweating,
• feeling short of breath,
• swelling or rapid weight gain,
• headache with chest pain and severe dizziness,
• fainting,
• fast or pounding heartbeats,
• bloody or tarry stools,
• coughing up blood,
• vomit that looks like coffee grounds,
• fever,
• sore throat,
• cough,
• flu symptoms,
• body aches,
• skin sores,
• pain or burning while urinating,
• severe headache,
• blurred vision,
• pounding in the neck or ears, and
• anxiety

Rare side effects of the Pazopanib include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Pazopanib has severe interactions with the following drugs:
  • aluminum hydroxide
  • atorvastatin
  • chloroquine
  • elagolix
  • lefamulin
• Pazopanib has serious interactions with at least 109 other drugs.
• Pazopanib has moderate interactions with at least 181 other drugs.
• Pazopanib has minor interactions with at least 23 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• None 

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Pazopanib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Pazopanib?”

Cautions

• Hepatotoxicity manifested as increases in ALT, AST, and bilirubin, occurred (see Black Box Warnings)
• Mild, indirect (unconjugated) hyperbilirubinemia may occur in patients with Gilbert’s syndrome; manage elevation in ALT above 3x ULN per dosing recommendations in such patients
• Fatal hemorrhage, fatal arterial thromboembolic events, and cerebral/intracranial hemorrhage have occurred
• Has not been studied in patients who have a history of hemoptysis, cerebral hemorrhage, patients who have had an arterial thromboembolic event within the previous 6 months, or clinically significant gastrointestinal hemorrhage in the past 6 months
• Venous thromboembolic events (VTEs), including venous thrombosis and fatal pulmonary embolus (PE), are reported; monitor for signs and symptoms of VTE and PE
• Thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), occurred in clinical trials
• Gastrointestinal perforation or fistula has been reported; monitor for signs and symptoms of gastrointestinal perforation or fistula; withhold in case of Grade 2 or 3 gastrointestinal fistulae and resume based on medical judgment; permanently discontinue in case of gastrointestinal perforation or Grade 4 gastrointestinal fistula
• ILD/pneumonitis and PRES, which can be fatal, have been reported
• Hypothyroidism has occurred; monitor thyroid tests at baseline, during treatment, and as clinically indicated and manage appropriately
• Proteinuria has been reported; perform baseline and periodic urinalysis during treatment with follow up measurement of 24-hr urine protein as clinically indicated
• Cases of TLS, including fatal cases, have been reported
• Can cause fetal harm when administered to a pregnant woman
• Serious infections (with or without neutropenia), some with fatal outcomes, are reported; monitor for signs and symptoms and treat active infection promptly; interrupt or discontinue therapy
• Based on its mechanism of action, pazopanib may have severe effects on organ growth and maturation during early postnatal development
• Not indicated for combination therapy; safe and effective combination dose has not been established
• Impaired wound healing
  • Impaired wound healing complications can occur; may have the potential to adversely affect wound healing
  • Withhold dose at least 1 week before elective surgery
  • Do not administer for at least 2 weeks following major surgery and until adequate wound healing
  • Safety of resuming therapy after resolution of wound healing complications has not been established
  • Hypertension
  • Hypertension (systolic blood pressure above 150 mmHg or diastolic blood pressure above 100 mmHg) and hypertensive crisis were observed
  • Do not initiate in patients with uncontrolled hypertension
  • Optimize blood pressure before initiating treatment
  • Monitor blood pressure as clinically indicated and initiate and adjust antihypertensive therapy as appropriate
  • Withhold and then reduce pazopanib dose or permanently discontinue based on the severity of hypertension
• Cardiac dysfunction
  • Cardiac dysfunction, including decreased LVEF and congestive heart failure, occurred
  • Monitor blood pressure and manage appropriately
  • 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
  • Withhold or permanently discontinue based on the severity of cardiac dysfunction
• QT prolongation
  • QT prolongation and Torsades de Pointes occurred
  • Monitor patients who are at significant risk of developing QTc prolongation, including patients with a history of QT interval prolongation, patients taking antiarrhythmics or other medications that may prolong QT interval, and those with relevant preexisting cardiac disease
  • Monitor ECG and electrolytes (eg, calcium, magnesium, potassium) at baseline and as clinically indicated. Correct electrolyte imbalances before initiating and during treatment
• Drug interaction overview
  • Pazopanib is CYP3A4, P-gp, and BCRP substrate; moderate CYP3A4, CYP2D6, and CYP2C8 inhibitor
  • Strong CYP3A4 inhibitors
    • Avoid coadministration
    • Strong CYP3A4 inhibitors increase pazopanib concentrations
    • If unable to avoid it, adjust the pazopanib dose
  • Strong CYP3A4 inducers
    • Avoid coadministration
    • Strong CYP3A4 inducers may decrease plasma pazopanib concentrations
  • Transporters
    • Avoid coadministration
    • Strong inhibitors of P-gp or BCRP may increase pazopanib concentrations
    • Consider the selection of alternative concomitant medicinal products with no or minimal potential to inhibit P-gp or BCRP
  • CYP3A4, CYP2D6, or CYP2C8 substrates with narrow therapeutic use
    • Not recommended
    • Coadministration with agents with narrow therapeutic windows that are metabolized by CYP3A4, CYP2D6, or CYP2C8 may inhibit the metabolism of these products and increase the risk for toxicities
  • Gastric acid-reducing agents
    • Avoid use
    • Coadministration with esomeprazole, a PPI, decreased the exposure of pazopanib
  • Simvastatin
    • Coadministration of simvastatin increases the risk of ALT elevations
    • Insufficient data are available to assess the risk of concomitant use of alternative statins with pazopanib
  • Drugs that prolong the QT interval
    • Avoid coadministration
    • Therapy is associated with QTc interval prolongation

Pregnancy and Lactation

• Based on animal studies and its mechanism of action, fetal harm may occur; advise pregnant women of the potential risk to a fetus
• No data available on use in pregnant females to evaluate drug-associated risk
• Verify the pregnancy status of females of reproductive potential before starting treatment
• Contraception
  • Females of reproductive potential: Use effective contraception during treatment and for at least 2 weeks after the last dose
  • Males (including those who have had vasectomies) with female partners of reproductive potential: Use condoms during treatment and for at least 2 weeks after the last dose
• Infertility
  • Based on findings from animal studies, fertility may be impaired in females and males of reproductive potential while receiving treatment
• Lactation
  • No data is available on the drug presence or its metabolites in human milk or the effects on the breastfed infant or milk production
  • Advise females not to breastfeed during treatment and for 2 weeks after the last dose