Pazopanib

Take the missed dose as soon as you remember it. However, if it is within 12 hours of your next scheduled dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Pregnancy

Based on animal reproduction studies and mechanism of action, it can cause fetal harm when administered to pregnant woman; there are no available data in pregnant women to inform drug-associated risk; in animal developmental and reproductive toxicology studies, oral administration of pazopanib to pregnant rats and rabbits throughout organogenesis resulted in teratogenicity, and abortion at systemic exposures lower than that observed at maximum recommended human dose of 800 mg (based on AUC); advise pregnant women or women of childbearing potential of potential risk to fetus

Lactation

There is no information regarding presence of drug or its metabolites in human milk, or effects on breastfed infant, or on milk production; because of potential for serious adverse reactions in breast- fed infants, advise a lactating woman not to breastfeed during treatment and for 2 weeks after final dose

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Grapefruit and grapefruit juice may interact with pazopanib and lead to unwanted side effects. Avoid the use of grapefruit products while taking pazopanib.

Ask your doctor before using an antacid, and use only the type your doctor recommends. Do not take an antacid within several hours before or after you have taken your pazopanib dose. Avoid taking stomach acid reducers (Axid, Nexium, Pepcid, Prevacid, Prilosec, Protonix, Tagamet, Zantac, Zegerid) while taking pazopanib.

This medicine can pass into body fluids (urine, feces, vomit). Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• an antibiotic;
• an antidepressant;
• cholesterol medicine that contains simvastatin (Zocor, Vytorin, Juvisync, Simcor);
• heart rhythm medication;
• HIV or AIDS medications; or
• stomach acid reducers such as Nexium, Prilosec, Tagamet, and others.

This list is not complete. Other drugs may interact with pazopanib, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Before you take pazopanib, tell your healthcare provider if you:

• have or had liver problems. You may need a lower dose of pazopanib or your healthcare provider may prescribe a different medicine to treat your advanced renal cell cancer or advanced soft tissue sarcoma.
• have high blood pressure
• have heart problems or an irregular heartbeat including QT prolongation
• have a history of a stroke
• have headaches, seizures, or vision problems
• have coughed up blood in the last 6 months
• had bleeding of your stomach or intestines in the last 6 months
• have a history of a tear (perforation) in your stomach or intestine, or an abnormal connection between two parts of your gastrointestinal tract (fistula)
• have had blood clots in a vein or in the lung
• have thyroid problems
• had recent surgery (within the last 7 days) or are going to have surgery
• have any other medical conditions
• are pregnant or plan to become pregnant.
• are breastfeeding or plan to breastfeed. 

Tell your healthcare provider about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Tell your healthcare provider if you are pregnant or plan to become pregnant. Pazopanib can harm your unborn baby. You should not become pregnant while you are taking pazopanib.

Grapefruit and grapefruit juice may interact with pazopanib and lead to unwanted side effects. Avoid the use of grapefruit products while taking pazopanib.

Ask your doctor before using an antacid, and use only the type your doctor recommends. Do not take an antacid within several hours before or after you have taken your pazopanib dose. Avoid taking stomach acid reducers (Axid, Nexium, Pepcid, Prevacid, Prilosec, Protonix, Tagamet, Zantac, Zegerid) while taking pazopanib.

This medicine can pass into body fluids (urine, feces, vomit). Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

It is very important that your doctor check your progress at regular visits for any unwanted effects from the medicine. Blood and urine tests may be needed to check for unwanted effects.

Your blood pressure should be checked regularly during treatment with pazopanib. Your doctor may need to treat you if you develop high blood pressure. Symptoms of high blood pressure are blurred vision, dizziness, nervousness, headache, pounding in the ears, or a slow or fast heartbeat.

Using pazopanib while you are pregnant can harm your unborn baby. It may also cause birth defects if the father is using it when his sexual partner becomes pregnant. Men and women should use an effective form of birth control to keep from getting pregnant during treatment with pazopanib and for at least 2 weeks after the last dose. If you think you have become pregnant while using the medicine, tell your doctor right away.

Cancer medicines can cause diarrhea, nausea, vomiting, or stomach pain in most people, sometimes even after receiving medicines to prevent it. Ask your doctor or nurse about other ways to control these unwanted effects.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea and vomiting, or yellow eyes or skin. These could be symptoms of a serious liver problem.

Contact your doctor right away if you have any changes to your heart rhythm. You might feel dizzy or faint, or you might have a fast, pounding, or uneven heartbeat. Make sure your doctor knows if you had a heart rhythm problem, such as QT prolongation.

Pazopanib may cause heart problems. Check with your doctor right away if you have chest pain or tightness, decreased urine output, dilated neck veins, extreme fatigue, irregular heartbeat, swelling of the face, fingers, feet, or lower legs, troubled breathing, or weight gain.

pazopanib may increase your risk of having bleeding problems. Tell your doctor right away if you start to notice any signs of bleeding.

pazopanib may affect the way your body heals from cuts and wounds. Make sure any doctor who treats you knows that you are using pazopanib. You may need to stop using pazopanib at least 7 days before having a surgery.

Check with your doctor right away if you have new chest pain, troubled breathing, leg pain, swelling of the arms, hands, legs, or feet, or a cool or pale arm or leg. These may be symptoms of a blood clotting problem.

Check with your doctor right away if you start having severe stomach burning, cramps, or pains, bloody or black, tarry stools, trouble breathing, heartburn, indigestion, nausea, or vomiting of material that looks like coffee grounds. These could be symptoms of a serious bowel problem.

pazopanib may cause swelling of the lungs (pneumonitis) or interstitial lung disease. These are life-threatening conditions and require immediate medical attention. The symptoms may be similar to the symptoms of lung cancer. Check with your doctor right away if you have new or worsening cough, fever, or trouble breathing.

pazopanib may increase your chance of having a brain condition called reversible posterior leukoencephalopathy syndrome (RPLS). Check with your doctor right away if you have headaches, seizures, extreme drowsiness, confusion, or vision problems while using pazopanib.

pazopanib may cause hypothyroidism (underactive thyroid). Check with your doctor right away if you have depressed mood, dry skin and hair, feeling cold, hair loss, hoarseness or a husky voice, muscle cramps and stiffness, slowed heartbeat, weight gain, or unusual tiredness or weakness.

Pazopanib may cause serious side effects in the developing organs of children younger than 2 years of age. Check with your doctor if you have any concerns.

Pazopanib may cause kidney problems, including proteinuria or nephrotic syndrome. Check with your doctor right away if you have a cloudy or bloody urine, high blood pressure, or swelling of the face, feet or lower legs.

Call your doctor right away if you have a cough that would not go away, weight loss, night sweats, fever, chills, or flu-like symptoms, such as a runny or stuffy nose, headache, blurred vision, or you feel generally ill. These may be symptoms of an infection.

pazopanib may cause diarrhea, and in some cases it can be severe. Do not take any medicine to treat diarrhea without first checking with your doctor. Diarrhea medicines may make the diarrhea worse or make it last longer. If you have any questions about this or if mild diarrhea continues or gets worse, check with your doctor.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

• Tell your doctor if you are taking any other cancer drugs. The chance of very bad and sometimes deadly side effects may be raised. Talk with your doctor.
• You may have more of a chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu. Some infections have been very bad and even deadly.
• Call your doctor right away if you have any signs of infection like fever, chills, flu-like signs, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or a wound that will not heal.
• A very bad and sometimes deadly brain problem called posterior reversible encephalopathy syndrome (PRES) has happened with this medicine. Call your doctor right away if you have signs like feeling confused, lowered alertness, change in eyesight, loss of eyesight, seizures, or very bad headache.
• Very bad and sometimes deadly holes in the GI (gastrointestinal) tract or fistulas have happened with pazopanib. Talk with the doctor.
• Very bad and sometimes deadly bleeding problems have happened with this medicine. Talk with the doctor.
• Blood clots have happened with pazopanib. Sometimes, blood clots like heart attack and stroke have been deadly. Talk with the doctor.
• Very bad and sometimes deadly blood problems like thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) have happened with this medicine in some people. Call your doctor right away if you feel very tired or weak or have any bruising or bleeding; dark urine or yellow skin or eyes; pale skin; change in the amount of urine passed; change in eyesight; change in strength on 1 side is greater than the other, trouble speaking or thinking, or change in balance; or fever.
• Very bad and sometimes deadly lung problems have happened with pazopanib. Call your doctor right away if you have lung or breathing problems that are new or worse like cough or shortness of breath.
• This medicine may affect fertility. Fertility problems may lead to not being able to get pregnant or father a child. Talk with the doctor.
• If you are a man and have sex with a female who could get pregnant, protect her from pregnancy during care and for 2 weeks after stopping this medicine. Use birth control that you can trust.
• If you are a man and your sex partner gets pregnant while you take pazopanib or within 2 weeks after your last dose, call your doctor right away.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant.
• If you are able to get pregnant, a pregnancy test will be done to show that you are NOT pregnant before starting this medicine. Talk with your doctor.
• Use birth control that you can trust to prevent pregnancy while taking pazopanib and for at least 2 weeks after stopping the drug.
• If you get pregnant while taking this medicine or within 2 weeks after your last dose, call your doctor right away.

(paz OH pa nib)

Cmax and AUC were 43% and 29%, respectively, of that observed in patients with moderate hepatic impairment administered a 200 mg dose compared with patients with normal hepatic function who received an 800 mg dose.

Thyroid cancer (advanced, differentiated)

Data from a phase II study supports the use of pazopanib in the treatment of advanced differentiated thyroid cancer [Bible 2010], [Bible 2014]. Additional trials may be necessary to further define the role of pazopanib in this condition.

Preexisting impairment:

Mild (bilirubin ≤1.5 times ULN or ALT >ULN): No dosage adjustment required (Shibata 2013).

Moderate (bilirubin >1.5 to 3 times ULN): Consider alternative therapy or reduce to 200 mg once daily (maximum tolerated dose in patients with moderate hepatic impairment) (Shibata 2013).

Severe (bilirubin >3 times ULN with any ALT level): Use is not recommended.

During treatment:

Isolated ALT elevations 3 to 8 times ULN: Continue treatment, monitor liver function weekly until ALT returns to grade 1 or baseline.

Isolated ALT elevations >8 times ULN: Interrupt treatment until ALT returns to grade 1 or baseline. If therapy benefit is greater than the risk of hepatotoxicity, may reinitiate treatment at ≤400 mg once daily (with liver function monitored weekly for 8 weeks); permanently discontinue if ALT >3 times ULN occurs with reinitiation.

ALT >3 times ULN concurrently with bilirubin >2 times ULN: Permanently discontinue; monitor until resolution.

Gilbert syndrome with mild indirect bilirubin elevation and ALT >3 times ULN: Refer to isolated ALT elevations dosage recommendations above.

Initial dosage reduction: Note: Prior to dose reduction, temporarily discontinue therapy if 24-hour urine protein ≥3 g or for other toxicities when clinically indicated.

RCC: Reduce to 400 mg once daily

STS: Reduce to 600 mg once daily

Further modification: RCC, STS: Adjust dose in 200 mg increments or decrements based on individual tolerance; maximum dose: 800 mg

Hypertension: Manage as appropriate with antihypertensive therapy and interrupt treatment or reduce dose as clinically warranted.

Hypertension (severe, persistent, and refractory to antihypertensives and dose reduction) or evidence of hypertensive crisis: Discontinue treatment.

Infection, serious: Consider treatment interruption or discontinuation.

Proteinuria (24-hour urine protein ≥3 g): Interrupt treatment and reduce the dose.

Proteinuria (recurrent 24-hour urine protein ≥3 g refractory to dose reduction): Discontinue treatment.

Pulmonary toxicity: Interstitial lung disease (ILD) or pneumonitis: Discontinue treatment.

Reversible posterior leukoencephalopathy syndrome (RPLS): Permanently discontinue.

Thrombotic microangiopathy (TMA): Permanently discontinue.

Wound dehiscence: Discontinue treatment.

Avoid grapefruit juice.

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

No adjustment recommended, but caution is recommended in patients with creatinine clearance below 30 mL/min.

-Mild hepatic impairment (either total bilirubin within normal limit with ALT greater than upper limit of normal [ULN] or bilirubin greater than 1 to 1.5 x ULN regardless of the ALT value): No adjustment required, but caution and close monitoring recommended.
-Moderate hepatic impairment (total bilirubin greater than 1.5 to 3 x ULN regardless of the ALT value): Consider alternative therapy or reduce dose to 200 mg orally once daily.
-Severe hepatic impairment (total bilirubin greater than 3 x ULN regardless of the ALT value): Not recommended.