your treatment handbook · 2018-01-15 · you should use effective birth control during your...

Inlyta is a prescription medicine used to treat advanced kidney cancer (advanced renal cell carcinoma or RCC) when one prior drug treatment for this disease has not worked or has stopped working. Please see Important Safety Information on pages 10-12, and full Prescribing Information and Patient Information, including a complete discussion of the risks of INLYTA, following this handbook.

Your treatment

handbook

Please see Important Safety Information on pages 10-12, and full Prescribing Information and Patient Information, including a complete discussion of the risks of INLYTA, following this handbook.

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this means different things to different people.

But what many advanced kidney cancer (advanced renal cell carcinoma or RCC) patients have in common is that desire to keep fighting. With that determination, your doctor’s support, and treatment with INLYTA, you now have the added confidence of this—you’re continuing your fight against advanced RCC.

Everyone has a this. A reason why they stay in the fight. For some, it’s about family. For others, friends. Or their favorite pastime. Their passion for work. Then there are the simple, incredible moments that make up every day.

03 about InLYta

Get helpful information you need about INLYTA, such as how it helps to fight tumors, how you should take INLYTA, and what you should tell your doctor before starting treatment.

10 Important Safety Information

Find out what you should tell your doctor before starting treatment and read about the risks and possible side effects of INLYTA.

13 Side effect tips

Learn about tips that may help to manage certain side effects of INLYTA.

17 access InLYta

Find information on how to get INLYTA, or how to get help paying for it.

19 advanced kidney Cancer

Read about the most common type of kidney cancer (advanced renal cell carcinoma or RCC), including how it starts and spreads.

21 more You Can do

Healthy choices you can make and where to find more support when you need it.

If you or someone you care about has been prescribed INLYTA, this handbook can help you learn about INLYTA and advanced RCC. Included in this handbook is the following information:

What You Will Find in this handbook


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About INLYTA® (axitinib) tablets

What is InLYta?

INLYTA (pronounced “in-LIGHT-ah”) was approved by the US Food and Drug Administration (FDA) on January 27, 2012. INLYTA is a prescription medicine used to treat advanced kidney cancer (advanced renal cell carcinoma or RCC) when one prior drug treatment for this disease has not worked or has stopped working.


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Important Safety InformationWomen should not take INLYTA if they are pregnant, plan to become pregnant, are breastfeeding, or plan to breastfeed. Taking INLYTA during pregnancy can cause the death of an unborn baby or birth defects. Both men and women taking INLYTA should use effective birth control during treatment with INLYTA. Talk to your doctor about birth control methods, or if you are pregnant or plan to become pregnant.

how InLYta helps fight tumors

In your body are 3 receptors called vascular endothelial growth factor (VEGF) receptors. These receptors play a role in how tumors grow and spread. The medicine in INLYTA is thought to work by targeting all 3 VEGF receptors. Animal and laboratory tests suggest that INLYTA binds to these receptors to help keep 2 basic actions of cancer, proliferation and angiogenesis, in check.


Stages of proliferation

Proliferation occurs when a cell divides to make more cells. In most organs of the body, the cells making up that organ tend to be the same size and shape. Cancer cells often proliferate at a much higher rate than normal cells and may grow in abnormal sizes and shapes.

Angiogenesis

Tumor

New blood vessel

Angiogenesis is the growth of new blood vessels. This occurs in healthy organs. But when it occurs in tumors, these blood vessels are abnormal and contribute to tumor growth.


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efficacy of treatment

INLYTA is a prescription medicine used to treat advanced kidney cancer (advanced renal cell carcinoma or RCC) when one prior drug treatment for this disease has not worked or has stopped working. This is often referred to as second-line treatment.


Nexavar is a registered trademark of Bayer Pharmaceuticals Corporation.

results from a head-to-head clinical trialIn a trial, INLYTA extended median progression-free survival (PFS) for some advanced RCC patients compared with others taking Nexavar® (sorafenib).

Extended median PFS by 2 months compared to Nexavar In this study, those who were treated with INLYTA experienced a median PFS of 6.7 months compared with 4.7 months among patients who were taking Nexavar. That’s a 43% increase in median PFS.

One-third less risk of progression In this study, the overall risk of disease progression, such as tumor growth or spread, or death, was decreased by about one-third with INLYTA compared to Nexavar.

INLYTA is not a cure. The data represent an average and not all patients may experience the same results.

Definitions

Progression-free survival (PFS): One measure of how a cancer treatment is working is what’s known as progression-free survival or PFS. This term refers to the length of time, from the start of treatment, that patients remain alive and their disease does not worsen.

Median: The median is a kind of average. Median PFS means that half of the patients in a study experienced longer PFS and half experienced shorter PFS.

Second-line treatment: A therapy prescribed when your first drug treatment has not worked or has stopped working.

Important Safety InformationINLYTA may cause serious side effects, including high blood pressure (hypertension), a problem with blood clots in your veins or arteries (sometimes leading to death), bleeding (sometimes leading to death), heart failure (sometimes leading to death), a tear (perforation) in your stomach or intestinal wall (sometimes leading to death), thyroid gland problems, reversible posterior leukoencephalopathy syndrome (RPLS), increased protein in your urine, and change in liver function.

(Continued on next page.)


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efficacy of treatment (Continued from previous page.)

INLYTA is a prescription medicine used to treat advanced kidney cancer (advanced renal cell carcinoma or RCC) when one prior drug treatment for this disease has not worked or has stopped working. This is often referred to as second-line treatment.


results from a head-to-head clinical trial

In a trial, INLYTA extended median progression-free survival (PFS) for some advanced RCC patients compared with others taking Nexavar® (sorafenib). (See page 5.)

Neither medicine showed an advantage in overall survival This study also measured the total time patients on each medicine remained alive after starting treatment. There was no significant difference in overall survival between the patients taking INLYTA and the patients taking Nexavar.

More than twice as many INLYTA patients saw their tumors shrink (overall response rate) Twice as many patients on INLYTA saw their tumors shrink (70 of 361 patients taking INLYTA compared with 34 of 362 patients taking Nexavar).

INLYTA is not a cure. The data represent an average and not all patients may experience the same results.

Important Safety InformationThe most common side effects of INLYTA include diarrhea (frequent or loose bowel movements); high blood pressure; tiredness or feeling weak; decreased appetite; nausea; hoarseness; rash, redness, itching or peeling of your skin on your hands or feet; decreased weight; vomiting; and constipation.

Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of INLYTA. For more information, ask your doctor or pharmacist.

Nexavar is a registered trademark of Bayer Pharmaceuticals Corporation.

Definitions

Overall survival: This is another measure of how a cancer treatment is working. It is the length of time that patients remain alive after starting treatment. This number includes all causes of death (cancer, treatment side effects, and other causes). It also includes time spent on later treatments.

Overall response rate: Another measure of how a cancer treatment is working is tumor shrinkage. This rate includes patients whose tumors shrank 30% or more and whose response lasted for at least 4 weeks. Doctors refer to tumor shrinkage as the overall tumor response rate.

Second-line treatment: A therapy prescribed when your first drug treatment has not worked or has stopped working.


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INLYTA is available as a tablet and offers the ease of being taken by mouth. Before starting INLYTA, it’s important to talk first with your doctor about any conditions you may have, as well as any medicines you might be taking.

before taking InLYta

Tell your doctor if you:

- Have high blood pressure

- Have thyroid problems

- Have liver problems

- Have a history of blood clots in your veins or arteries (types of blood vessels), including stroke, heart attack, or change in vision


For females, tell your doctor if you:

- Are pregnant or plan to become pregnant. Taking INLYTA during pregnancy can cause the death of an unborn baby or birth defects. You should not become pregnant while taking INLYTA. Talk to your doctor if you are pregnant or plan to become pregnant

- Are able to become pregnant. You should use effective birth control during your treatment with INLYTA. Talk to your doctor about birth control methods to prevent pregnancy while you are taking INLYTA

- Are breastfeeding or plan to breastfeed. It is not known if INLYTA passes into your breast milk. You and your doctor should decide if you will take INLYTA or breastfeed. You should not do both

For males:

- Use effective birth control during your treatment with INLYTA. Talk to your doctor about birth control methods

- If your female partner becomes pregnant while you are taking INLYTA, tell your doctor right away

- Have any bleeding problems

- Have a history of heart failure

- Have an unhealed wound

- Plan to have surgery. You should stop taking INLYTA at least 24 hours before planned surgery

- Have any other medical conditions


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Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. INLYTA and certain other medicines can affect each other causing serious side effects.

Especially tell your doctor if you take:

Dexamethasone Bosentan Modafi nil St. John’s wort (Hypericum perforatum)

Medicine for:

- Asthma - Seizures - Fungal infections - HIV/AIDS

- Tuberculosis - Bacterial infections - Depression

Ask your doctor or pharmacist if you are not sure if your medicine is one listed above. If you are taking any medicines for the conditions listed above, your doctor might need to prescribe a different medicine or your dose of INLYTA may need to be changed. Talk with your doctor before you start taking any new medicine.

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

Grapefruit-Free ZoneDo not drink grapefruit juice or eat grapefruit. Grapefruit may increase the amount of INLYTA in your blood.

How to take INLYTA

INLYTA comes in 1-mg and 5-mg tablets. Your doctor will tell you which tablets you should take.

- Take INLYTA exactly as prescribed by your doctor

- Your doctor may change your dose if needed

- INLYTA can be taken with or without food

- Take INLYTA 2 times a day approximately 12 hours apart

- Swallow INLYTA tablets whole with a glass of water

- Your doctor should check your blood pressure regularly during treatment with INLYTA

- If you vomit or miss a dose of INLYTA, take your next dose at your regular time. Do not take 2 doses at the same time

- If you take too much INLYTA, call your doctor or go to the nearest hospital emergency room right away

1 mg

5 mg


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helpful reminders for taking each dose

Make medicine a part of your daily routine. Take your medicine every day at the same times, 12 hours apart. For example, you may want to take it when you wake up in the morning and just after dinner

Use a weekly or monthly pill caddy. It can help you keep count of your tablets in advance, and to remember to take each day’s dosage

Plan ahead. If possible, get your refills before your next treatment cycle starts

Place your pill bottle in plain sight. Keep your medicine where you will see it, such as on your nightstand. Just make sure it is out of the reach of children and pets

Always carry an extra dose with you. No matter where you are, you will always have your medicine on hand

Use a calendar. Record your dosage times on a calendar or planner. You can then check off each dose as you take it

Use a journal to track your medicine and when it is time to take it. You can also use it to track symptoms and side effects for doctor visits

Ask for a reminder. A caregiver, friend, or family member can help remind you to take each dose of your medicine. Just ask


Work with your healthcare team

It’s important to optimize the time you have with your healthcare team. Here are 3 tips to help you get organized and make the most of doctor visits:

Use a journal to note your other medicines, questions, and experiences with your disease and treatment. That way, you can share them with your healthcare team.

Speak your mind. Be sure your healthcare team knows when you have questions or want more information. Never be afraid to reach out and express yourself.

Store direct office numbers and e-mail addresses for your healthcare team in one convenient place. Having this information handy will save you time when you have a question.

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Please see full Prescribing Information and Patient Information, including a complete discussion of the risks of INLYTA, following this handbook.

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review important safety information prior to taking InLYta

When starting treatment with INLYTA, it’s important that you review the safety information in this section. Inside, you will find information you should share with your doctor before taking INLYTA. You will also see a list of the risks and possible side effects associated with INLYTA.

make note of all your side effects and how you’re feeling

Be sure to pay attention to all your side effects. They can be important signs that let you and your doctor know what is happening in your body.

Before starting INLYTA, tell your doctor how you are feeling and about any side effects you have had from other medicines and treatments. As you start taking INLYTA, let your doctor know if you notice any side effects or a change in how you feel. Also tell your doctor if you notice any side effects that are not listed in this brochure. Based on your experience, your doctor may change your dose or stop treatment with INLYTA.

Important Safety Information


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Important safety information

Before you take INLYTA, tell your doctor if you:- Have high blood pressure

- Have thyroid problems

- Have liver problems

- Have a history of blood clots in your veins or arteries (types of blood vessels), including stroke, heart attack, or change in vision

Tell your doctor and pharmacist about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. INLYTA and certain other medicines can affect each other causing serious side effects. Talk with your doctor before you start taking any new medicine.

Especially tell your doctor if you take dexamethasone, bosentan, modafinil, St. John’s wort (Hypericum perforatum), or medicine for asthma, tuberculosis, seizures, bacterial infections, fungal infections, depression, or HIV/AIDS.

Do not drink grapefruit juice or eat grapefruit.

Pregnancy and breastfeeding. Women should not take INLYTA if they are pregnant, plan to become pregnant, are breastfeeding, or plan to breastfeed. Taking INLYTA during pregnancy can cause the death of an unborn baby or birth defects. Both men and women taking INLYTA should use effective birth control during treatment with INLYTA. Talk to your doctor about birth control methods, or if you are pregnant or plan to become pregnant.

INLYTA may cause serious side effects, including: High blood pressure (hypertension). In a clinical study, hypertension occurred as early as 4 days into treatment. On average, this increase was seen within the first month of treatment. Your doctor should check your blood pressure regularly during treatment with INLYTA. If you develop blood pressure problems, your doctor may prescribe medicine to treat your high blood pressure, loweryour dose, or stop your treatment with INLYTA

Problem with blood clots in your veins or arteries. Because this can be serious and sometimes lead to death, get emergency help and call your doctor if you get any of the following symptoms:- Chest pain or pressure- Pain in your arms, back,

neck or jaw

Bleeding. INLYTA can cause bleeding which can be serious, and sometimes lead to death. Call your doctor right away or get medical help if you develop any of the following signs or symptoms:- Unexpected bleeding or bleeding that lasts a long time, such as:

- Unusual bleeding from the gums

- Menstrual bleeding or vaginal bleeding that is heavier than normal

- Bleeding that is severe or you cannot control

- Pink or brown urine

- Unexpected pain, swelling, or joint pain

- Headaches, feeling dizzy or weak

- Have any bleeding problems

- Have a history of heart failure

- Have an unhealed wound

- Plan to have surgery. You should stop taking INLYTA at least 24 hours before planned surgery

- Have any other medical conditions

- Shortness of breath

- Numbness or weakness on one side of your body

- Trouble talking

- Headache

- Vision changes

- Red or black stools (looks like tar)- Bruises that happen without a known cause or get larger- Cough up blood or blood clots- Vomit blood or your vomit looks like “coffee grounds”

(Continued on next page.)


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Heart failure. Your doctor should check for signs or symptoms of heart failure regularly during treatment with INLYTA. Heart failure can be serious and can sometimes lead to death. Tell your doctor if you have any of the following symptoms during your treatment with INLYTA:- Tiredness- Swelling of your stomach area (abdomen), legs, or ankles

Tear in your stomach or intestinal wall (perforation). Because this can be serious and sometimes lead to death, get medical help right away if you get the following symptoms:- Severe stomach (abdominal) pain or stomach pain that does not go away- Vomit blood- Red or black stools

Thyroid gland problems. Your doctor should do blood tests to check your thyroid gland function before and during your treatment with INLYTA. Tell your doctor if you have any of the following symptoms during your treatment with INLYTA:- Tiredness that worsens or that does not go away - Weight gain or weight loss- Feeling hot or cold - Hair loss- Your voice deepens - Muscle cramps and aches

(Continued from previous page.)

Reversible Posterior Leukoencephalopathy Syndrome (RPLS). A condition called reversible posterior leukoencephalopathy syndrome (RPLS) can happen while taking INLYTA. Call your doctor right away if you get:- Headache - Confusion - Blindness or change in vision- Seizures - High blood pressure - Problems thinking- Weakness

Increased protein in your urine. Your doctor should check your urine for protein before and during your treatment with INLYTA. If you develop protein in your urine, your doctor may decrease your dose of INLYTA or stop your treatment Change in liver function. Your doctor should do blood tests before and during your treatment with INLYTA to check your liver function The most common side effects of INLYTA include:- Diarrhea (frequent or

loose bowel movements)- High blood pressure- Tiredness or feeling weak

Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of INLYTA. For more information, ask your doctor or pharmacist.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

- Decreased appetite - Nausea- Hoarseness

- Rash, redness, itching or peeling of your skin on your hands or feet

- Decreased weight- Vomiting- Constipation

- Shortness of breath- Protruding neck veins


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High blood pressure

In a clinical study, hypertension occurred as early as 4 days into treatment. On average, this increase was seen within the first month of treatment. INLYTA may cause your blood pressure to rise.

Your doctor should check your blood pressure regularly while you are being treated with INLYTA. If you develop blood pressure problems, your doctor may prescribe medicine to treat your high blood pressure, lower your dose, or stop your treatment with INLYTA. Tell your doctor or nurse if you have high blood pressure or a history of heart disease.

If you have high blood pressure, your healthcare provider’s recommendations may include:

If you are already being treated for your high blood pressure, your doctor may change your blood pressure medicine when you start taking INLYTA. Your doctor may also ask you to track your blood pressure regularly. Follow the advice of your doctor or nurse—talk to them if you have any questions or concerns.

- Take antihypertensive medications as prescribed

- Recognize signs of potentially dangerous high blood pressure (eg, severe headache, shortness of breath, nosebleeds)

- Follow healthy lifestyle choices: regular exercise, weight control, moderate alcohol consumption, sodium restriction

Side Effect Tips

Ways to help manage certain common side effects

The tips in this section are based on published general guidelines for managing side effects common among people with advanced RCC or other cancers.

Not all side effects are manageable. Dose interruptions and/or reductions may be needed during treatment with INLYTA. Be sure to talk to your healthcare professional about any side effects you experience and how they may be managed for you.


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Side Effect Tips

Diarrhea

Diarrhea is more loose or watery stools/bowel movements than usual. If you have these symptoms, call your doctor or nurse. It is important for you and your doctor to try to manage diarrhea as soon as it begins.

If you experience diarrhea, your healthcare provider’s recommendations may include:

- Try yogurt containing probiotics

- Eat foods containing soluble fiber

- Eat small but frequent meals

- Drink fluids, such as water, diluted cranberry juice, broth, or decaffeinated tea or coffee

- Ask your doctor or nurse if you can be treated with over-the-counter medications

Tiredness or feeling weak

While you are taking INLYTA, you may feel tired or weak. Call your doctor or nurse if you have these symptoms.

If tiredness or feeling weak is a recurring problem, your healthcare provider’s recommendations may include:

- Take short naps and breaks instead of long ones

- Eat well and drink plenty of fluids

- Take short walks or do light exercise if you feel up to it

- Do things that are relaxing, such as listening to music or reading

- Stay as active as possible

- Try to maintain normal work and social schedules

- Ask your doctor if there are over-the-counter or prescription medications that may help you manage your condition


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Side Effect Tips

Decreased appetite or weightDuring treatment, you may have less desire to eat. But maintaining good nutrition and a healthy weight are important to your overall health. Protein and calories are even more vital to someone with cancer.If you have decreased appetite, you can discuss the following diet ideas with your doctor:- Eat several small meals a day—5 or 6 isn’t out

of the question- When you are hungry, eat- Enjoy snacks and strive to make them

nutritious. Find calories and protein in dried fruits, nuts, cheeses, and even milkshakes

- For added protein and calories, it can be a good idea to add gravy, butter, or cheese to your favorite foods

- Drink fluids between meals rather than filling up with them during meals

- If you are too tired to cook, ask a friend or family member to make you something. You may be surprised how many people are willing to help you

- If mouth pain causes you to eat less, consider avoiding spicy foods. Eat foods that are soft or use a straw for liquids

- If taste changes cause you to eat less, try cold or frozen foods to minimize taste. Flavor foods with herbs, sugar, or sauces to maximize taste. And keep a clean and healthy mouth by brushing and flossing often

- If an upset stomach causes you to eat less, avoid heavy meals, coffee, and alcohol; try sleeping in an upright position; and reduce stress with meditation, yoga, or music

- A registered dietitian (RD) may have more ideas to offer you

Ask your doctor if there are over-the-counter or prescription medicines that may help you manage your condition.

Nausea or vomiting

It is best to call your doctor or nurse at the first sign of nausea or vomiting. This is especially important if these symptoms keep you from taking your oral medications, or keeping them down. Your healthcare provider may prescribe a medicine for these symptoms.If you experience nausea or vomiting, your healthcare provider’s recommendations may include:

If you vomit, start with small amounts of water, broth, or other clear liquids when you are ready to eat again. If that stays down, then try soft foods. Some examples include gelatin, plain cornstarch pudding, yogurt, strained soup, or strained cooked cereal. Slowly work up to eating solid food. Make sure that you do not eat any food that you are allergic to.

- Avoid fatty, fried, spicy, or highly sweet foods

- Eat bland foods and drink clear liquids- Eat smaller, more frequent meals

- Reduce food aromas and other stimuli with strong odors, and eat food at room temperature to lessen the odor

- Listen to soft music, watch a favorite television program, or enjoy the company of others while you eat


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Side Effect Tips

Hoarseness

Also called dysphonia (dis-phone-ee-uh), this is when you have a weak, rough, or harsh voice.

If you have trouble speaking, your healthcare provider’s recommendations may include:- Drink plenty of water and avoid irritants

(eg, dust, smoke, alcohol, industrial chemicals)- Give your voice a break—write things down

- Avoid voice strain through shouting or whispering

Skin conditions

Skin conditions, such as rash, redness, or itching or peeling of skin, are other side effects you may have. You may notice dryness, thickening, calluses, or cracking of the skin on the palms of your hands and soles of your feet. This is called hand-foot syndrome. Some patients may have blisters or a rash. Tell your doctor or nurse if you start to develop skin problems. He or she may give you specific treatments, which may include lotions, moisturizers, or pain medicines.

To help manage the effects of hand-foot syndrome, your healthcare provider’s recommendations may include:- Wear loose cotton clothes- Use sunscreen- Clean hands and feet with lukewarm water

and gently pat dry

- Apply creams containing lanolin or urea to the hands and feet liberally and often

- Avoid tight-fitting shoes and jewelry or rubbing pressure on the hands and feet

- Do not shave off blisters

Constipation

Some people taking INLYTA experience constipation. This has the potential to become a serious side effect. Left untreated, constipation can cause a blockage in your intestines, leading to dehydration and even internal damage.

If you experience constipation, speak to your doctor. He or she may recommend any of the following:- Drinking more fluids- Taking a stool softener- Changing your dose of INLYTA

- Adding fiber to your diet- Increasing physical activity- Getting an enema


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Learn about getting access to InLYta

INLYTA is available through Specialty Pharmacy Providers (SPP). These are pharmacies that handle medicines not often on hand at regular neighborhood pharmacies. If you need help determining which SPP to use, your doctor’s office should be able to help you find one that’s right for your insurance.

You or your doctor’s office can also call Pfizer RxPathways™ at 1-866-706-2400. One of its Patient Care Coordinators may be able to help you or your doctor’s office identify an appropriate SPP. They will ask you a few basic questions, including your insurance information, before they identify an appropriate SPP.

Access INLYTA® (axitinib) tablets


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Your co-pay could be covered.*

If your prescription is covered by your insurance, but you need help with your co-pay, the INLYTA Co-Pay One Savings Card may be able to assist you.

Insured patients who demonstrate signifi cant fi nancial hardship and meet income eligibility requirements can apply for the INLYTA Co-Pay One Savings Card. Many patients who qualify will receive help to cover the full cost of their co-pay.

* Limits, terms, and conditions apply. Co-pay program is also available to cash-paying patients. The maximum annual savings of $25,000 still applies. This offer is not health insurance. No membership fees. The offer will be accepted only at participating pharmacies. Please see the full terms and conditions online.

Access INLYTA® (axitinib) tablets

† Proof of income is required to validate patient household income. Proof of income includes items such as the most recent federal income tax return, W-2 form(s), Social Security check, or a copy of the most recent pay stub. Proof of income is required within 30 days of enrollment.

Are you uninsured? Patients who are uninsured may be able to get their Pfi zer medicine for free through the Pfi zer RxPathways Patient Assistance Program.

To be eligible, patients must:• Have no prescription coverage• Meet specifi c income guidelines, adjusted for family size†

• Reside in the United States, US Virgin Islands, or Puerto Rico• Be treated by a licensed physician in the United States or Puerto Rico

If you need help right away or just want more information, please contact your Specialty Pharmacy Provider or visit INLYTA.com today.

Visit www.inlyta.com/access-inlyta to learn about the INLYTA Co-Pay One Savings Card, and see if you’re eligible

to start saving on your INLYTA prescriptions.


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INLYTA is a prescription medicine used to treat advanced kidney cancer (advanced renal cell carcinoma or RCC) when one prior drug treatment for this disease has not worked or has stopped working.

RCC is the most common type of kidney cancer. RCC starts in the kidney. It can start as one or more tumors in a single kidney. Less often, tumors form in both kidneys at the same time.

how rCC starts and spreads

Cancer cells are abnormal versions of healthy cells. They grow in many ways like these normal cells but do so at abnormal rates with irregular shapes.

How these cells grow and spread:

A single RCC cell grows and divides to form 2 cells. This process repeats, again and again

A tumor can be detected once enough cancer cells are made

Some cancer cells may enter the bloodstream, spreading from the kidney to other parts of the body

New tumors may spread to other organs. If this happens, the cancer is known as metastatic. But no matter where the cancer spreads, it will still be called RCC, because it started in the kidney

RCC—The Most Common Type of Kidney Cancer


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Stages of rCC

There are 4 stages of RCC. To determine the cancer’s stage, doctors will measure the tumor size. The images below are examples of different tumor sizes.

Stage

Stage I

Stage II

Stage III

Stage IV

Recurrent RCC

Images are notactual size

Definition

Tumor is found only in the kidney and is 7 centimeters or smaller.

Tumor is found only in the kidney and is larger than 7 centimeters.

Cancer may be found in the kidney, one nearby lymph node, an adrenal gland, the tissue around the kidney, or the main blood vessels of the kidneys.

Cancer has spread beyond the kidney and may be found in multiple nearby lymph nodes or other organs, such as the intestines, pancreas, or lungs.

Recurrent RCC is cancer that has returned after it has been treated, coming back in the kidney and/or in other parts of the body after the first treatment.

Golf ball (5 cm) Tennis ball (7 cm)

RCC—The Most Common Type of Kidney Cancer


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It may seem like there’s the disease and the treatment—and nothing else. But there are many things you can do to try and focus on what makes you happy and potentially feel better. There are also groups out there that offer support to people living with cancer.

help outside the doctor’s office

These healthy living tips are general information for anyone fighting cancer.

Resting enough

It’s no secret that cancer and its treatment can wear you down. But for some, these changes can make it difficult to get rest. It’s important to discuss changes in your sleep with your healthcare team.

There are a few tips that may help you get rest if you are not sleeping enough. Taking a bath or shower, or listening to soothing music, before bedtime may help. Also, try taking short naps or breaks during the day.

Staying active

While cancer and its treatment can cause fatigue, it’s still important to try and stay active. Ask your doctor before starting any activities. He or she may suggest simple ways to add exercise to your daily life.

More You Can Do


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80Reducing stress Obviously, cancer takes a mental as well as physical toll. That can make it hard for you to simply be you. But if you think about the tips below, you may find a way to fight back, with old friends like food, relaxation, and more.

- Try and relax: whether that means taking a deep breath, meditating, or praying, take moments for yourself

- See if you are able to get more rest and exercise: review the tips on the previous page; they also happen to be good stress-busters

- If you’re comfortable, open up to people you trust: from friends and family members to therapists and religious leaders, sharing your feelings may ease the burden you carry

- Eat what you love: just make sure to talk it over with your doctor so you don’t adversely affect your health or treatment

- Try to remember fun: watch comedies, spend time with friends, family and pets, and always try to keep the L-word in mind—Laughter

Staying informedIf you’re up for it, try and learn all you can about your type of cancer. Find reliable and credible resources for the latest, most current information about cancer and its treatment. Think about taking these steps:

- First, talk openly with your healthcare team: track your symptoms and side effects. Alert your doctor about any changes, reactions, or side effects you may have

- Be as organized as possible; log your activities and/or doctor appointments in a journal for easy reference, and include your insurance information

Stop smokingIf you are a current smoker, quitting now may improve your overall health. According to the National Cancer Institute:

- Continuing to smoke may decrease the effectiveness of treatment and may worsen treatment side effects

- If you have surgery for your cancer, continuing to smoke may cause your wounds to heal more slowly

Talk to your doctor about quitting smoking.

Eat rightIt’s important to maintain a healthy weight and eat a well-balanced diet that includes more fruits, fresh vegetables, whole grains, and high-fiber foods.

- Many people with cancer don’t take in enough protein and calories. Getting a healthy balance of each can give you a better chance of healing well, fighting off infection, and maintaining your energy level

- Along with protein, a healthy diet also includes nutrients, vitamins, minerals, carbohydrates, water, and fat. All can help to better support the body

- Good nutrition and a healthy diet may help you to better manage the symptoms and side effects of cancer and its treatment

More You Can Do


23

more resources and support for you

In addition to allowing friends and loved ones to offer their help, think about this: living with cancer can cause you to have a wide range of emotions, including depression. Talking to others who live with cancer may help you cope with the challenges and changes that it can bring.

The following list of organizations and resources are provided to help you learn more about cancer and where to tap into patient support services.

The American Cancer Society® (ACS)(800) 227-2345 | cancer.orgGet helpful advice and up-to-date news about treatment options and clinical studies, as well as inspirational stories from cancer survivors.

National Cancer Institute® (NCI)(800) 422-6237 | cancer.govThis helpful resource offers facts and information about cancer, treatments, and clinical trials. It also provides advice on how to pay for treatment, as well as choosing hospice and home care, and how to find support groups.

CancerCare®

(800) 813-HOPE (813-4673) | cancercare.orgGet helpful advice and counseling about cancer, such as disease information and free financial services.

Cancer Hope Network(877) HOPENET (467-3638)cancerhopenetwork.orgSupport services for people living with cancer, which include matching patients one-on-one with cancer survivors.

Kidney Cancer Association® (KCA)(800) 850-9132 | kidneycancer.orgA dedicated group of patients, families, doctors, and healthcare providers involved with kidney cancer and its treatment. Learn simple ways to make living with kidney cancer easier, and how to find and connect with other patients and survivors.

More You Can Do

These organizations and resources are neither owned nor controlled by Pfizer. Pfizer is not responsible for their content or services.

keep this in mind

Get InLYta

INLYTA is available through a specialty pharmacy. If you are having trouble getting or paying for INLYTA, talk to your doctor or call Pfizer RxPathways™ at 1-866-706-2400.

Work with your healthcare team

Pay attention to how you’re feeling as you take INLYTA. If you have side effects, your doctor or nurse may have ideas to help you manage them.

use this handbook as a guide

The information and tips in this brochure may help you as you start out with INLYTA. Keep it with you. If you have questions, ask your healthcare team for more information.

For more information, please visit INLYTA.com.

This Is About More Than Cancer

Visit INLYTA.com today. And be sure to check back for the most up-to-date information about INLYTA and advanced renal cell carcinoma (RCC).

Inlyta is a prescription medicine used to treat advanced kidney cancer (advanced renal cell carcinoma or RCC) when one prior drug treatment for this disease has not worked or has stopped working.

AXU692712-01 © 2014 Pfizer Inc. All rights reserved. November 2014


FULL PRESCRIBING INFORMATION1 INDICATIONS AND USAGE

INLYTA is indicated for the treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy.

2 DOSAGE AND ADMINISTRATION2.1 Recommended DosingThe recommended starting oral dose of INLYTA is 5 mg twice daily. Administer INLYTA

doses approximately 12 hours apart with or without food [see Clinical Pharmacology(12.3)]. INLYTA should be swallowed whole with a glass of water.

If the patient vomits or misses a dose, an additional dose should not be taken. Thenext prescribed dose should be taken at the usual time.

2.2 Dose Modification GuidelinesDose increase or reduction is recommended based on individual safety and tolerability.Over the course of treatment, patients who tolerate INLYTA for at least two consecutive

weeks with no adverse reactions >Grade 2 (according to the Common Toxicity Criteria forAdverse Events [CTCAE]), are normotensive, and are not receiving anti-hypertension medication, may have their dose increased. When a dose increase from 5 mg twice daily isrecommended, the INLYTA dose may be increased to 7 mg twice daily, and further to 10 mgtwice daily using the same criteria.

Over the course of treatment, management of some adverse drug reactions may require temporary interruption or permanent discontinuation and/or dose reduction of INLYTA therapy [see Warnings and Precautions (5)]. If dose reduction from 5 mg twice

daily is required, the recommended dose is 3 mg twice daily. If additional dose reductionis required, the recommended dose is 2 mg twice daily.

Strong CYP3A4/5 Inhibitors: The concomitant use of strong CYP3A4/5 inhibitorsshould be avoided (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir,nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole). Selection ofan alternate concomitant medication with no or minimal CYP3A4/5 inhibition potential isrecommended. Although INLYTA dose adjustment has not been studied in patients receivingstrong CYP3A4/5 inhibitors, if a strong CYP3A4/5 inhibitor must be co-administered, adose decrease of INLYTA by approximately half is recommended, as this dose reduction ispredicted to adjust the axitinib area under the plasma concentration vs time curve (AUC)to the range observed without inhibitors. The subsequent doses can be increased or decreased based on individual safety and tolerability. If co-administration of the strong inhibitor is discontinued, the INLYTA dose should be returned (after 3 – 5 half-lives of the inhibitor) to that used prior to initiation of the strong CYP3A4/5 inhibitor [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

Hepatic Impairment: No starting dose adjustment is required when administering INLYTA to patients with mild hepatic impairment (Child-Pugh class A). Based on the pharmaco kinetic data, the INLYTA starting dose should be reduced by approximately halfin patients with baseline moderate hepatic impairment (Child-Pugh class B). The subsequentdoses can be increased or decreased based on individual safety and tolerability. INLYTA has notbeen studied in patients with severe hepatic impairment (Child-Pugh class C) [see Warningsand Precautions (5.12), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].

FULL PRESCRIBING INFORMATION: CONTENTS*1 INDICATIONS AND USAGE2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosing2.2 Dose Modification Guidelines

3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS

5.1 Hypertension and Hypertensive Crisis5.2 Arterial Thromboembolic Events5.3 Venous Thromboembolic Events5.4 Hemorrhage5.5 Cardiac Failure5.6 Gastrointestinal Perforation and Fistula Formation5.7 Thyroid Dysfunction5.8 Wound Healing Complications5.9 Reversible Posterior Leukoencephalopathy Syndrome5.10 Proteinuria5.11 Elevation of Liver Enzymes5.12 Hepatic Impairment5.13 Pregnancy

6 ADVERSE REACTIONS6.1 Clinical Trials Experience

7 DRUG INTERACTIONS7.1 CYP3A4/5 Inhibitors7.2 CYP3A4/5 Inducers

8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy

8.3 Nursing Mothers8.4 Pediatric Use8.5 Geriatric Use8.6 Hepatic Impairment8.7 Renal Impairment

10 OVERDOSAGE11 DESCRIPTION12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action12.2 Pharmacodynamics12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING INFORMATION

17.1 Hypertension17.2 Arterial/Venous Thromboembolic Events17.3 Hemorrhage17.4 Cardiac Failure17.5 Gastrointestinal Disorders17.6 Abnormal Thyroid Function17.7 Wound Healing Complications17.8 Reversible Posterior Leukoencephalopathy Syndrome17.9 Pregnancy17.10 Concomitant Medications

*Sections or subsections omitted from the Full Prescribing Information are not listed.

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use INLYTA safely and effectively. See full prescribing information for INLYTA.INLYTA® (axitinib) tablets for oral administrationInitial U.S. Approval: 2012--------------------------------------------RECENT MAJOR CHANGES-------------------------------------------Warnings and Precautions, Cardiac Failure (5.5) 08/2014--------------------------------------------INDICATIONS AND USAGE-------------------------------------------INLYTA is a kinase inhibitor indicated for the treatment of advanced renal cell carcinoma afterfailure of one prior systemic therapy. (1)---------------------------------------DOSAGE AND ADMINISTRATION----------------------------------------• The starting dose is 5 mg orally twice daily. Dose adjustments can be made based on

individual safety and tolerability. (2.1, 2.2)• Administer INLYTA dose approximately 12 hours apart with or without food. (2.1)• INLYTA should be swallowed whole with a glass of water. (2.1)• If a strong CYP3A4/5 inhibitor is required, decrease the INLYTA dose by approximately

half. (2.2)• For patients with moderate hepatic impairment, decrease the starting dose by approx-

imately half. (2.2)--------------------------------------DOSAGE FORMS AND STRENGTHS---------------------------------------1 mg and 5 mg tablets (3)-----------------------------------------------CONTRAINDICATIONS----------------------------------------------None (4)----------------------------------------WARNINGS AND PRECAUTIONS----------------------------------------• Hypertension including hypertensive crisis has been observed. Blood pressure should

be well-controlled prior to initiating INLYTA. Monitor for hypertension and treat asneeded. For persistent hypertension despite use of anti-hypertensive medications, reduce the INLYTA dose. (5.1)

• Arterial and venous thrombotic events have been observed and can be fatal. Use withcaution in patients who are at increased risk for these events. (5.2, 5.3)

• Hemorrhagic events, including fatal events, have been reported. INLYTA has not been studied in patients with evidence of untreated brain metastasis or recent activegastrointestinal bleeding and should not be used in those patients. (5.4)

• Cardiac failure has been observed and can be fatal. Monitor for signs or symptoms ofcardiac failure throughout treatment with INLYTA. (5.5)

• Gastrointestinal perforation and fistula, including death, have occurred. Use with cautionin patients at risk for gastrointestinal perforation or fistula. (5.6)

• Hypothyroidism requiring thyroid hormone replacement has been reported. Monitor thyroid function before initiation of, and periodically throughout, treatment with INLYTA.(5.7)

• Stop INLYTA at least 24 hours prior to scheduled surgery. (5.8)• Reversible Posterior Leukoencephalopathy Syndrome (RPLS) has been observed.

Permanently discontinue INLYTA if signs or symptoms of RPLS occur. (5.9)• Monitor for proteinuria before initiation of, and periodically throughout, treatment with

INLYTA. For moderate to severe proteinuria, reduce the dose or temporarily interrupttreatment with INLYTA. (5.10)

• Liver enzyme elevation has been observed during treatment with INLYTA. Monitor ALT,AST and bilirubin before initiation of, and periodically throughout, treatment with INLYTA. (5.11)

• The starting dose of INLYTA should be decreased if used in patients with moderate hepatic impairment. INLYTA has not been studied in patients with severe hepatic impairment. (2.2, 5.12)

• INLYTA can cause fetal harm when administered to a pregnant woman based on its mechanism of action. Women of childbearing potential should be advised of the potentialhazard to the fetus and to avoid becoming pregnant while receiving INLYTA. (5.13, 8.1)

----------------------------------------------ADVERSE REACTIONS---------------------------------------------The most common (≥20%) adverse reactions are diarrhea, hypertension, fatigue, decreasedappetite, nausea, dysphonia, palmar-plantar erythrodysesthesia (hand-foot) syndrome,weight decreased, vomiting, asthenia, and constipation. (6.1)To report SUSPECTED ADVERSE REACTIONS, contact Pfizer, Inc at 1-800-438-1985 orFDA at 1-800-FDA-1088 or www.fda.gov/medwatch.----------------------------------------------DRUG INTERACTIONS----------------------------------------------• Avoid strong CYP3A4/5 inhibitors. If unavoidable, reduce the INLYTA dose. (2.2, 7.1)• Avoid strong CYP3A4/5 inducers. (7.2)See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling

Revised: 8/2014

3 DOSAGE FORMS AND STRENGTHS1 mg tablets of INLYTA: red, film-coated, oval tablets, debossed with “Pfizer” on one

side and “1 XNB” on the other side.5 mg tablets of INLYTA: red, film-coated, triangular tablets, debossed with “Pfizer” on

one side and “5 XNB” on the other side.

4 CONTRAINDICATIONSNone

5 WARNINGS AND PRECAUTIONS5.1 Hypertension and Hypertensive CrisisIn a controlled clinical study with INLYTA for the treatment of patients with RCC, hyper -

tension was reported in 145/359 patients (40%) receiving INLYTA and 103/355 patients(29%) receiving sorafenib. Grade 3/4 hypertension was observed in 56/359 patients (16%) receiving INLYTA and 39/355 patients (11%) receiving sorafenib. Hypertensive crisis wasreported in 2/359 patients (<1%) receiving INLYTA and none of the patients receiving sorafenib. The median onset time for hypertension (systolic blood pressure >150 mmHgor diastolic blood pressure >100 mmHg) was within the first month of the start of INLYTAtreatment and blood pressure increases have been observed as early as 4 days after starting INLYTA. Hypertension was managed with standard antihypertensive therapy. Discontinuation of INLYTA treatment due to hypertension occurred in 1/359 patients (<1%)receiving INLYTA and none of the patients receiving sorafenib [see Adverse Reactions(6.1)].

Blood pressure should be well-controlled prior to initiating INLYTA. Patients shouldbe monitored for hypertension and treated as needed with standard anti-hypertensive therapy. In the case of persistent hypertension despite use of anti-hypertensive medications, reduce the INLYTA dose. Discontinue INLYTA if hypertension is severe and persistent despite anti-hypertensive therapy and dose reduction of INLYTA, and discontinuation should be considered if there is evidence of hypertensive crisis. If INLYTAis interrupted, patients receiving antihypertensive medications should be monitored for hypotension [see Dosage and Administration (2.2)].

5.2 Arterial Thromboembolic EventsIn clinical trials, arterial thromboembolic events have been reported, including deaths.

In a controlled clinical study with INLYTA for the treatment of patients with RCC, Grade 3/4 arterial thromboembolic events were reported in 4/359 patients (1%) receiving INLYTA and4/355 patients (1%) receiving sorafenib. Fatal cerebrovascular accident was reported in1/359 patients (<1%) receiving INLYTA and none of the patients receiving sorafenib [see Adverse Reactions (6.1)].

In clinical trials with INLYTA, arterial thromboembolic events (including transient ischemic attack, cerebrovascular accident, myocardial infarction, and retinal artery occlusion)were reported in 17/715 patients (2%), with two deaths secondary to cerebrovascular accident.

Use INLYTA with caution in patients who are at risk for, or who have a history of,these events. INLYTA has not been studied in patients who had an arterial thromboembolicevent within the previous 12 months.

5.3 Venous Thromboembolic EventsIn clinical trials, venous thromboembolic events have been reported, including deaths.

In a controlled clinical study with INLYTA for the treatment of patients with RCC, venousthromboembolic events were reported in 11/359 patients (3%) receiving INLYTA and 2/355patients (1%) receiving sorafenib. Grade 3/4 venous thromboembolic events were reportedin 9/359 patients (3%) receiving INLYTA (including pulmonary embolism, deep vein thrombosis, retinal vein occlusion and retinal vein thrombosis) and 2/355 patients (1%) receiving sorafenib. Fatal pulmonary embolism was reported in 1/359 patients (<1%) receiving INLYTA and none of the patients receiving sorafenib. In clinical trials with INLYTA,venous thromboembolic events were reported in 22/715 patients (3%), with two deathssecondary to pulmonary embolism.

Use INLYTA with caution in patients who are at risk for, or who have a history of,these events. INLYTA has not been studied in patients who had a venous thromboembolicevent within the previous 6 months.

5.4 HemorrhageIn a controlled clinical study with INLYTA for the treatment of patients with RCC,

hemorrhagic events were reported in 58/359 patients (16%) receiving INLYTA and 64/355patients (18%) receiving sorafenib. Grade 3/4 hemorrhagic events were reported in 5/359(1%) patients receiving INLYTA (including cerebral hemorrhage, hematuria, hemoptysis,lower gastrointestinal hemorrhage, and melena) and 11/355 (3%) patients receiving sorafenib. Fatal hemorrhage was reported in 1/359 patients (<1%) receiving INLYTA (gastric hemorrhage) and 3/355 patients (1%) receiving sorafenib.

INLYTA has not been studied in patients who have evidence of untreated brain metastasis or recent active gastrointestinal bleeding and should not be used in those patients. If any bleeding requires medical intervention, temporarily interrupt the INLYTA dose.

5.5 Cardiac FailureIn a controlled clinical study with INLYTA for the treatment of patients with RCC, cardiac

failure was reported in 6/359 patients (2%) receiving INLYTA and 3/355 patients (1%) receiving sorafenib. Grade 3/4 cardiac failure was observed in 2/359 patients (1%) receivingINLYTA and 1/355 patients (<1%) receiving sorafenib. Fatal cardiac failure was reported in2/359 patients (1%) receiving INLYTA and 1/355 patients (<1%) receiving sorafenib. Monitor for signs or symptoms of cardiac failure throughout treatment with INLYTA. Management of cardiac failure may require permanent discontinuation of INLYTA.

5.6 Gastrointestinal Perforation and Fistula FormationIn a controlled clinical study with INLYTA for the treatment of patients with RCC,

gastro intestinal perforation was reported in 1/359 patients (<1%) receiving INLYTA andnone of the patients receiving sorafenib. In clinical trials with INLYTA, gastrointestinal perforation was reported in 5/715 patients (1%), including one death. In addition to casesof gastro intestinal perforation, fistulas were reported in 4/715 patients (1%).

Monitor for symptoms of gastrointestinal perforation or fistula periodically throughouttreatment with INLYTA.

5.7 Thyroid DysfunctionIn a controlled clinical study with INLYTA for the treatment of patients with RCC,

hypo thyroidism was reported in 69/359 patients (19%) receiving INLYTA and 29/355 patients (8%) receiving sorafenib. Hyperthyroidism was reported in 4/359 patients (1%) receiving INLYTA and 4/355 patients (1%) receiving sorafenib. In patients who had thyroid stimulating hormone (TSH) <5 µU/mL before treatment, elevations of TSH to ≥10 µU/mL occurred in 79/245 patients (32%) receiving INLYTA and 25/232 patients (11%) receiving sorafenib [see Adverse Reactions (6.1)].

Monitor thyroid function before initiation of, and periodically throughout, treatmentwith INLYTA. Treat hypothyroidism and hyperthyroidism according to standard medical practice to maintain euthyroid state.

5.8 Wound Healing ComplicationsNo formal studies of the effect of INLYTA on wound healing have been conducted.Stop treatment with INLYTA at least 24 hours prior to scheduled surgery. The

decision to resume INLYTA therapy after surgery should be based on clinical judgment ofadequate wound healing.

5.9 Reversible Posterior Leukoencephalopathy SyndromeIn a controlled clinical study with INLYTA for the treatment of patients with RCC,

reversible posterior leukoencephalopathy syndrome (RPLS) was reported in 1/359 patients(<1%) receiving INLYTA and none of the patients receiving sorafenib [see Adverse Reac-tions (6.1)]. There were two additional reports of RPLS in other clinical trials with INLYTA.

RPLS is a neurological disorder which can present with headache, seizure, lethargy, confusion, blindness and other visual and neurologic disturbances. Mild to severe hyper-tension may be present. Magnetic resonance imaging is necessary to confirm the diagnosis of RPLS. Discontinue INLYTA in patients developing RPLS. The safety of reinitiatingINLYTA therapy in patients previously experiencing RPLS is not known.

5.10 ProteinuriaIn a controlled clinical study with INLYTA for the treatment of patients with RCC,

proteinuria was reported in 39/359 patients (11%) receiving INLYTA and 26/355 patients (7%)receiving sorafenib. Grade 3 proteinuria was reported in 11/359 patients (3%) receiving INLYTA and 6/355 patients (2%) receiving sorafenib [see Adverse Reactions (6.1)].

Monitoring for proteinuria before initiation of, and periodically throughout, treatmentwith INLYTA is recommended. For patients who develop moderate to severe proteinuria, reduce the dose or temporarily interrupt INLYTA treatment.

5.11 Elevation of Liver EnzymesIn a controlled clinical study with INLYTA for the treatment of patients with RCC,

alanine aminotransferase (ALT) elevations of all grades occurred in 22% of patients on botharms, with Grade 3/4 events in <1% of patients on the INLYTA arm and 2% of patients onthe sorafenib arm.

Monitor ALT, aspartate aminotransferase (AST) and bilirubin before initiation of and periodically throughout treatment with INLYTA.

5.12 Hepatic ImpairmentThe systemic exposure to axitinib was higher in subjects with moderate hepatic

impairment (Child-Pugh class B) compared to subjects with normal hepatic function. Adose decrease is recommended when administering INLYTA to patients with moderate hepatic impairment (Child-Pugh class B). INLYTA has not been studied in patients with severe hepatic impairment (Child-Pugh class C) [see Dosage and Administration (2.2), Usein Specific Populations (8.6), and Clinical Pharmacology (12.3)].

5.13 PregnancyINLYTA can cause fetal harm when administered to a pregnant woman based on its

mechanism of action. There are no adequate and well-controlled studies in pregnant womenusing INLYTA. In developmental toxicity studies in mice, axitinib was teratogenic, embryotoxic and fetotoxic at maternal exposures that were lower than human exposures atthe recommended clinical dose.

Women of childbearing potential should be advised to avoid becoming pregnant while receiving INLYTA. If this drug is used during pregnancy, or if a patient becomes pregnantwhile receiving this drug, the patient should be apprised of the potential hazard to the fetus[see Use in Specific Populations (8.1)].6 ADVERSE REACTIONS

Because clinical trials are conducted under widely varying conditions, adverse reactionrates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The safety of INLYTA has been evaluated in 715 patients in monotherapy studies,which included 537 patients with advanced RCC. The data described [see Adverse Reac-tions (6.1)] reflect exposure to INLYTA in 359 patients with advanced RCC who participatedin a randomized clinical study versus sorafenib [see Clinical Studies (14)].

The following risks, including appropriate action to be taken, are discussed in greater detail in other sections of the label [see Warnings and Precautions (5.1-5.13)]: hypertension,arterial thromboembolic events, venous thromboembolic events, hemorrhage, cardiac failure, gastrointestinal perforation and fistula formation, thyroid dysfunction, wound healingcomplications, RPLS, proteinuria, elevation of liver enzymes, hepatic impairment and fetaldevelopment.

6.1 Clinical Trials ExperienceThe median duration of treatment was 6.4 months (range 0.03 to 22.0) for patients

who received INLYTA and 5.0 months (range 0.03 to 20.1) for patients who received sorafenib. Dose modifications or temporary delay of treatment due to an adverse reactionoccurred in 199/359 patients (55%) receiving INLYTA and 220/355 patients (62%) receiving sorafenib. Permanent discontinuation due to an adverse reaction occurred in34/359 patients (9%) receiving INLYTA and 46/355 patients (13%) receiving sorafenib.

The most common (≥20%) adverse reactions observed following treatment with INLYTA were diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, palmar-plantar erythrodysesthesia (hand-foot) syndrome, weight decreased, vomiting, asthenia, and constipation. Table 1 presents adverse reactions reported in ≥10% patientswho received INLYTA or sorafenib.

Table 1. Adverse Reactions Occurring in ≥10% of Patients Who Received INLYTA or SorafenibINLYTA Sorafenib(N=359) (N=355)

Adverse Reactiona All Grade All GradeGradesb 3/4 Gradesb 3/4

% % % %Diarrhea 55 11 53 7Hypertension 40 16 29 11Fatigue 39 11 32 5Decreased appetite 34 5 29 4Nausea 32 3 22 1Dysphonia 31 0 14 0Palmar-plantar erythrodysesthesia syndrome 27 5 51 16Weight decreased 25 2 21 1Vomiting 24 3 17 1Asthenia 21 5 14 3Constipation 20 1 20 1Hypothyroidism 19 <1 8 0Cough 15 1 17 1Mucosal inflammation 15 1 12 1Arthralgia 15 2 11 1Stomatitis 15 1 12 <1Dyspnea 15 3 12 3Abdominal pain 14 2 11 1Headache 14 1 11 0Pain in extremity 13 1 14 1Rash 13 <1 32 4Proteinuria 11 3 7 2Dysgeusia 11 0 8 0Dry skin 10 0 11 0Dyspepsia 10 0 2 0Pruritus 7 0 12 0Alopecia 4 0 32 0Erythema 2 0 10 <1a Percentages are treatment-emergent, all-causality eventsb National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0

Selected adverse reactions (all grades) that were reported in <10% of patients treatedwith INLYTA included dizziness (9%), upper abdominal pain (8%), myalgia (7%), dehydration(6%), epistaxis (6%), anemia (4%), hemorrhoids (4%), hematuria (3%), tinnitus (3%), lipase increased (3%), glossodynia (3%), pulmonary embolism (2%), rectal hemorrhage(2%), hemoptysis (2%), deep vein thrombosis (1%), retinal-vein occlusion/thrombosis (1%),polycythemia (1%), and transient ischemic attack (1%).

Table 2 presents the most common laboratory abnormalities reported in ≥10% patients who received INLYTA or sorafenib.Table 2. Laboratory Abnormalities Occurring in ≥10% of Patients Who Received INLYTA

or SorafenibINLYTA Sorafenib

Laboratory All Grade All Grade Abnormality N Gradesa 3/4 N Gradesa 3/4

% % % %HematologyHemoglobin decreased 320 35 <1 316 52 4Lymphocytes (absolute) decreased 317 33 3 309 36 4Platelets decreased 312 15 <1 310 14 0White blood cells decreased 320 11 0 315 16 <1ChemistryCreatinine increased 336 55 0 318 41 <1Bicarbonate decreased 314 44 <1 291 43 0Hypocalcemia 336 39 1 319 59 2ALP increased 336 30 1 319 34 1Hyperglycemia 336 28 2 319 23 2Lipase increased 338 27 5 319 46 15Amylase increased 338 25 2 319 33 2ALT increased 331 22 <1 313 22 2AST increased 331 20 <1 311 25 1Hypernatremia 338 17 1 319 13 1Hypoalbuminemia 337 15 <1 319 18 1Hyperkalemia 333 15 3 314 10 3Hypoglycemia 336 11 <1 319 8 <1Hyponatremia 338 13 4 319 11 2Hypophosphatemia 336 13 2 318 49 16a National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0ALP: alkaline phosphatase; ALT: alanine aminotransferase; AST: aspartate aminotransferase

Selected laboratory abnormalities (all grades) that were reported in <10% of patientstreated with INLYTA included hemoglobin increased (above the upper limit of normal) (9% for INLYTA versus 1% for sorafenib) and hypercalcemia (6% for INLYTA versus 2% forsorafenib).7 DRUG INTERACTIONS

In vitro data indicate that axitinib is metabolized primarily by CYP3A4/5 and, to a lesser extent, CYP1A2, CYP2C19, and uridine diphosphate-glucuronosyltransferase (UGT) 1A1.

7.1 CYP3A4/5 InhibitorsCo-administration of ketoconazole, a strong inhibitor of CYP3A4/5, increased the

plasma exposure of axitinib in healthy volunteers. Co-administration of INLYTA with strongCYP3A4/5 inhibitors should be avoided. Grapefruit or grapefruit juice may also increaseaxitinib plasma concentrations and should be avoided. Selection of concomitant medicationwith no or minimal CYP3A4/5 inhibition potential is recommended. If a strong CYP3A4/5inhibitor must be co-administered, the INLYTA dose should be reduced [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].

7.2 CYP3A4/5 InducersCo-administration of rifampin, a strong inducer of CYP3A4/5, reduced the plasma

exposure of axitinib in healthy volunteers. Co-administration of INLYTA with strong CYP3A4/5 inducers (e.g., rifampin, dexamethasone, phenytoin, carbamazepine, rifabutin, rifapentin,phenobarbital, and St. John’s wort) should be avoided. Selection of concomitant medication withno or minimal CYP3A4/5 induction potential is recommended [see Dosage and Administration(2.2) and Clinical Pharmacology (12.3)]. Moderate CYP3A4/5 inducers (e.g., bosentan,efavirenz, etravirine, modafinil, and nafcillin) may also reduce the plasma exposure of axitiniband should be avoided if possible.8 USE IN SPECIFIC POPULATIONS

8.1 PregnancyPregnancy Category D [see Warnings and Precautions (5.13)].There are no adequate and well-controlled studies with INLYTA in pregnant women.

INLYTA can cause fetal harm when administered to a pregnant woman based on its mechanism of action. Axitinib was teratogenic, embryotoxic and fetotoxic in mice at exposures lower than human exposures at the recommended starting dose. If this drug isused during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus.

Oral axitinib administered twice daily to female mice prior to mating and through the first week of pregnancy caused an increase in post-implantation loss at all doses tested(≥15 mg/kg/dose, approximately 10 times the systemic exposure [AUC] in patients at therecommended starting dose). In an embryo-fetal developmental toxicity study, pregnantmice received oral doses of 0.15, 0.5 and 1.5 mg/kg/dose axitinib twice daily during the period of organogenesis. Embryo-fetal toxicities observed in the absence of maternal toxicity included malformation (cleft palate) at 1.5 mg/kg/dose (approximately 0.5 timesthe AUC in patients at the recommended starting dose) and variation in skeletal ossificationat ≥0.5 mg/kg/dose (approximately 0.15 times the AUC in patients at the recommendedstarting dose).

8.3 Nursing MothersIt is not known whether axitinib is excreted in human milk. Because many drugs are

excreted in human milk and because of the potential for serious adverse reactions in nursing infants from INLYTA, a decision should be made whether to discontinue nursing orto discontinue the drug, taking into account the importance of the drug to the mother.

8.4 Pediatric UseThe safety and efficacy of INLYTA in pediatric patients have not been studied.Toxicities in bone and teeth were observed in immature mice and dogs administered

oral axitinib twice daily for 1 month or longer. Effects in bone consisted of thickened growthplates in mice and dogs at ≥15 mg/kg/dose (approximately 6 and 15 times, respectively, thesystemic exposure [AUC] in patients at the recommended starting dose). Abnormalities ingrowing incisor teeth (including dental caries, malocclusions and broken and/or missingteeth) were observed in mice administered oral axitinib twice daily at ≥5 mg/kg/dose (approximately 1.5 times the AUC in patients at the recommended starting dose). Othertoxicities of potential concern to pediatric patients have not been evaluated in juvenile animals.

8.5 Geriatric UseIn a controlled clinical study with INLYTA for the treatment of patients with RCC, 123/359

patients (34%) treated with INLYTA were ≥65 years of age. Although greater sensitivity insome older individuals cannot be ruled out, no overall differences were observed in the safetyand effectiveness of INLYTA between patients who were ≥65 years of age and younger.

No dosage adjustment is required in elderly patients [see Dosage and Administration(2.2) and Clinical Pharmacology (12.3)].

8.6 Hepatic ImpairmentIn a dedicated hepatic impairment trial, compared to subjects with normal hepatic

function, systemic exposure following a single dose of INLYTA was similar in subjects withbaseline mild hepatic impairment (Child-Pugh class A) and higher in subjects with baselinemoderate hepatic impairment (Child-Pugh class B).

No starting dose adjustment is required when administering INLYTA to patients withmild hepatic impairment (Child-Pugh class A). A starting dose decrease is recommendedwhen administering INLYTA to patients with moderate hepatic impairment (Child-Pugh classB) [see Dosage and Administration (2.2), Warnings and Precautions (5.12), and Clinical Pharmacology (12.3)].

INLYTA has not been studied in subjects with severe hepatic impairment (Child-Pugh class C).

8.7 Renal ImpairmentNo dedicated renal impairment trial for axitinib has been conducted. Based on

the population pharmacokinetic analyses, no significant difference in axitinib clearance was observed in patients with pre-existing mild to severe renal impairment (15 mL/min≤creatinine clearance [CLcr] <89 mL/min) [see Clinical Pharmacology (12.3)]. No startingdose adjustment is needed for patients with pre-existing mild to severe renal impairment. Caution should be used in patients with end-stage renal disease (CLcr <15 mL/min).

10 OVERDOSAGEThere is no specific treatment for INLYTA overdose.In a controlled clinical study with INLYTA for the treatment of patients with RCC,

1 patient inadvertently received a dose of 20 mg twice daily for 4 days and experienced dizziness (Grade 1).

In a clinical dose finding study with INLYTA, subjects who received starting doses of10 mg twice daily or 20 mg twice daily experienced adverse reactions which included hypertension, seizures associated with hypertension, and fatal hemoptysis.

In cases of suspected overdose, INLYTA should be withheld and supportive care instituted.

11 DESCRIPTIONINLYTA (axitinib) is a kinase inhibitor. Axitinib has the chemical name N-methyl-2-[3-

((E)-2-pyridin-2-yl-vinyl)-1H-indazol-6-ylsulfanyl]-benzamide. The molecular formula isC22H18N4OS and the molecular weight is 386.47 Daltons. The chemical structure is:

Axitinib is a white to light-yellow powder with a pKa of 4.8. The solubility of axitinibin aqueous media over the range pH 1.1 to pH 7.8 is in excess of 0.2 µg/mL. The partition coefficient (n-octanol/water) is 3.5.

INLYTA is supplied as red, film-coated tablets containing either 1 mg or 5 mg of axitinib together with microcrystalline cellulose, lactose monohydrate, croscarmellosesodium, magnesium stearate, and Opadry® II red 32K15441 as inactive ingredients. TheOpadry II red 32K15441 film coating contains lactose monohydrate, HPMC 2910/Hypro -mellose 15cP, titanium dioxide, triacetin (glycerol triacetate), and red iron oxide.12 CLINICAL PHARMACOLOGY

12.1 Mechanism of ActionAxitinib has been shown to inhibit receptor tyrosine kinases including vascular

endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3 at therapeuticplasma concentrations. These receptors are implicated in pathologic angiogenesis, tumorgrowth, and cancer progression. VEGF-mediated endothelial cell proliferation and survivalwere inhibited by axitinib in vitro and in mouse models. Axitinib was shown to inhibit tumorgrowth and phosphorylation of VEGFR-2 in tumor xenograft mouse models.

12.2 PharmacodynamicsThe effect of a single oral dose of INLYTA (5 mg) in the absence and presence of

400 mg ketoconazole on the QTc interval was evaluated in a randomized, single-blinded,two-way crossover study in 35 healthy subjects. No large changes in mean QTc interval(i.e., >20 ms) from placebo were detected up to 3 hours post-dose. However, small increases in mean QTc interval (i.e., <10 ms) cannot be ruled out.

12.3 PharmacokineticsThe population pharmacokinetic analysis pooled data from 17 trials in healthy

subjects and patients with cancer. A two-compartment disposition model with first-orderabsorption and lag-time adequately describes the axitinib concentration-time profile.

Absorption and Distribution: Following single oral 5-mg dose administration, the median Tmax ranged from 2.5 to 4.1 hours. Based on the plasma half-life, steady state is expected within 2 to 3 days of dosing. Dosing of axitinib at 5 mg twice daily resulted in approximately 1.4-fold accumulation compared to administration of a single dose. At steadystate, axitinib exhibits approximately linear pharmacokinetics within the 1-mg to 20-mgdose range. The mean absolute bioavailability of axitinib after an oral 5 mg dose is 58%.

Compared to overnight fasting, administration of INLYTA with a moderate fat mealresulted in 10% lower AUC and a high fat, high-calorie meal resulted in 19% higher AUC.INLYTA can be administered with or without food [see Dosage and Administration (2.1)].

Axitinib is highly bound (>99%) to human plasma proteins with preferential bindingto albumin and moderate binding to a1-acid glycoprotein. In patients with advanced RCC(n=20), at the 5 mg twice daily dose in the fed state, the geometric mean (CV%) Cmax and AUC0-24 were 27.8 (79%) ng/mL and 265 (77%) ng.h/mL, respectively. The geometric mean (CV%) clearance and apparent volume of distribution were 38 (80%) L/hand 160 (105%) L, respectively.

Metabolism and Elimination: The plasma half life of INLYTA ranges from 2.5 to 6.1hours. Axitinib is metabolized primarily in the liver by CYP3A4/5 and to a lesser extent byCYP1A2, CYP2C19, and UGT1A1. Following oral administration of a 5-mg radioactive doseof axitinib, approximately 41% of the radioactivity was recovered in feces and approxi-mately 23% was recovered in urine. Unchanged axitinib, accounting for 12% of the dose,was the major component identified in feces. Unchanged axitinib was not detected in urine;the carboxylic acid and sulfoxide metabolites accounted for the majority of radioactivity inurine. In plasma, the N-glucuronide metabolite represented the predominant radioactivecomponent (50% of circulating radioactivity) and unchanged axitinib and the sulfoxidemetabolite each accounted for approximately 20% of the circulating radioactivity.

The sulfoxide and N-glucuronide metabolites show approximately ≥400-fold less in vitro potency against VEGFR-2 compared to axitinib.

Drug-Drug InteractionsEffects of Other Drugs on INLYTA: Axitinib is metabolized primarily in the liver by

CYP3A4/5. Additionally, the aqueous solubility of axitinib is pH dependent, with higher pHresulting in lower solubility. The effects of a strong CYP3A4/5 inhibitor, a strong CYP3A4/5inducer, and an antacid on the pharmacokinetics of axitinib are presented in Figure 1 [seeDosage and Administration (2.2) and Drug Interactions (7.1, 7.2)].

Figure 1. Impact of Co-administered Drugs and Hepatic Impairment on Axitinib Pharmacokinetics

Effects of INLYTA on Other Drugs: In vitro studies demonstrated that axitinib has the potential to inhibit CYP1A2 and CYP2C8. However, co-administration of axitinib with paclitaxel, a CYP2C8 substrate, did not increase plasma concentrations of paclitaxel in patients.

In vitro studies indicated that axitinib does not inhibit CYP2A6, CYP2C9, CYP2C19,CYP2D6, CYP2E1, CYP3A4/5, or UGT1A1 at therapeutic plasma concentrations. In vitrostudies in human hepatocytes indicated that axitinib does not induce CYP1A1, CYP1A2, orCYP3A4/5.

Axitinib is an inhibitor of the efflux transporter P-glycoprotein (P-gp) in vitro. However,INLYTA is not expected to inhibit P-gp at therapeutic plasma concentrations.

Pharmacokinetics in Specific PopulationsPediatric Use: INLYTA has not been studied in patients <18 years of age.Hepatic Impairment: The effects of hepatic impairment on the pharmacokinetics of

axitinib are presented in Figure 1 [see Dosage and Administration (2.2), Warnings and Precautions (5.12), and Use in Specific Populations (8.6)].

Renal Impairment: Population pharmacokinetic analysis (based on pre-existing renal function) was carried out in 590 healthy volunteers and patients, including five with severerenal impairment (15 mL/min ≤CLcr <29 mL/min), 64 with moderate renal impairment (30 mL/min ≤CLcr <59 mL/min), and 139 with mild renal impairment (60 mL/min ≤CLcr<89 mL/min). Mild to severe renal impairment did not have meaningful effects on the pharmacokinetics of axitinib. Data from only one patient with end-stage renal disease areavailable [see Use in Specific Populations (8.7)].

Other Intrinsic Factors: Population pharmacokinetic analyses indicate that there areno clinically relevant effects of age, gender, race, body weight, body surface area, UGT1A1genotype, or CYP2C19 genotype on the clearance of axitinib.13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityCarcinogenicity studies have not been conducted with axitinib.Axitinib was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay and

was not clastogenic in the in vitro human lymphocyte chromosome aberration assay. Axitinib was genotoxic in the in vivo mouse bone marrow micronucleus assay.

INLYTA has the potential to impair reproductive function and fertility in humans. In repeat-dose toxicology studies, findings in the male reproductive tract were observed in thetestes/epididymis (decreased organ weight, atrophy or degeneration, decreased numbersof germinal cells, hypospermia or abnormal sperm forms, reduced sperm density and count) at ≥15 mg/kg/dose administered orally twice daily in mice (approximately 7 times the systemic exposure (AUC) in patients at the recommended starting dose) and≥1.5 mg/kg/dose administered orally twice daily in dogs (approximately 0.1 times the AUCin patients at the recommended starting dose). Findings in the female reproductive tract inmice and dogs included signs of delayed sexual maturity, reduced or absent corpora lutea,decreased uterine weights and uterine atrophy at ≥5 mg/kg/dose (approximately 1.5 or 0.3 times the AUC in patients at the recommended starting dose compared to mice anddogs, respectively).

In a fertility study in mice, axitinib did not affect mating or fertility rate when admin-istered orally twice daily to males at any dose tested up to 50 mg/kg/dose following at least70 days of administration (approximately 57 times the AUC in patients at the recommendedstarting dose). In female mice, reduced fertility and embryonic viability were observed atall doses tested (≥15 mg/kg/dose administered orally twice daily) following at least 15 daysof treatment with axitinib (approximately 10 times the AUC in patients at the recommendedstarting dose).

14 CLINICAL STUDIESThe safety and efficacy of INLYTA were evaluated in a randomized, open-label,

multicenter Phase 3 study. Patients (N=723) with advanced RCC whose disease had progressed on or after treatment with 1 prior systemic therapy, including sunitinib-, bevacizumab-, temsirolimus-, or cytokine-containing regimens were randomized (1:1) to receive INLYTA (N=361) or sorafenib (N=362). Progression-free survival (PFS) was assessed by a blinded independent central review committee. Other endpoints included objective response rate (ORR) and overall survival (OS).

Of the patients enrolled in this study, 389 patients (54%) had received 1 prior sunitinib-based therapy, 251 patients (35%) had received 1 prior cytokine-based therapy (interleukin-2 orinterferon-alfa), 59 patients (8%) had received 1 prior bevacizumab-based therapy, and 24 patients (3%) had received 1 prior temsirolimus-based therapy. The baseline demographic anddisease characteristics were similar between the INLYTA and sorafenib groups with regard toage (median 61 years), gender (72% male), race (75% white, 21% Asian), Eastern CooperativeOncology Group (ECOG) performance status (55% 0, 45% 1), and histology (99% clear cell).

There was a statistically significant advantage for INLYTA over sorafenib for the endpoint of PFS (see Table 3 and Figure 2). There was no statistically significant differencebetween the arms in OS.Table 3. Efficacy ResultsEndpoint/Study Population INLYTA Sorafenib HR (95% CI) P-valueOverall ITT N= 361 N = 362Median PFSa,b in months 6.7 (6.3, 8.6) 4.7 (4.6, 5.6) 0.67 (0.54, 0.81) <0.0001c(95% CI)Median OS in months 20.1 (16.7, 23.4) 19.2 (17.5, 22.3) 0.97 (0.80, 1.17) NS(95% CI)ORR % (95% CI) 19.4 (15.4, 23.9) 9.4 (6.6, 12.9) 2.06d (1.41, 3.00) -ePFS by prior treatmentSunitinib-refractory N=194 N=195subgroupMedian, months (95% CI) 4.8 (4.5, 6.4) 3.4 (2.8, 4.7) 0.74 (0.57, 0.96) -e

Cytokine-refractory N=126 N=125subgroupMedian, months (95% CI) 12.1 (10.1, 13.9) 6.5 (6.3, 8.3) 0.46 (0.32, 0.68) -e

CI: Confidence interval; HR: Hazard ratio (INLYTA/sorafenib); ITT: Intent to treat; ORR: Objectiveresponse rate; NS: Not significant; OS: Overall survival; PFS: Progression-free survivala Time from randomization to progression or death due to any cause, whichever occurs first.b Assessed by independent radiology review according to RECIST.c One-sided p-value from a log-rank test of treatment stratified by ECOG performance status andprior therapy (comparison is considered statistically significant if the one-sided p-value is <0.023).d Risk ratio is used for ORR. A risk ratio >1 indicated a higher likelihood of responding in the axitinib arm; a risk ratio <1 indicated a higher likelihood of responding in the sorafenib arm.e P-value not included since it was not adjusted for multiple testing.Figure 2. Kaplan-Meier Curve for Progression Free Survival by Independent Assessment

(Intent-to-Treat Population)

16 HOW SUPPLIED/STORAGE AND HANDLINGINLYTA tablets are supplied as follows:1 mg tablets are red film-coated, oval tablets debossed with “Pfizer” on one side and

“1 XNB” on the other; available in bottles of 180: NDC 0069-0145-01.5 mg tablets are red film-coated, triangular tablets debossed with “Pfizer” on one side

and “5 XNB” on the other; available in bottles of 60: NDC 0069-0151-11.Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to

86°F) [see USP Controlled Room Temperature].17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information)17.1 HypertensionAdvise patients that hypertension may develop during INLYTA treatment and that blood

pressure should be monitored regularly during treatment [see Warnings and Precautions (5.1)].17.2 Arterial/Venous Thromboembolic EventsAdvise patients that arterial and venous thromboembolic events have been observed

during INLYTA treatment and to inform their doctor if they experience symptoms suggestive of thromboembolic events [see Warnings and Precautions (5.2, 5.3)].

17.3 HemorrhageAdvise patients that INLYTA may increase the risk of bleeding and to promptly inform

their doctor of any bleeding episodes [see Warnings and Precautions (5.4)].17.4 Cardiac FailureAdvise patients that cardiac failure may develop during INLYTA treatment and that

signs or symptoms of cardiac failure should be regularly monitored for during treatment[see Warnings and Precautions (5.5)].

17.5 Gastrointestinal DisordersAdvise patients that gastrointestinal disorders such as diarrhea, nausea, vomiting,

and constipation may develop during INLYTA treatment and to seek immediate medical attention if they experience persistent or severe abdominal pain because cases of gastrointestinal perforation and fistula have been reported in patients taking INLYTA [seeWarnings and Precautions (5.6) and Adverse Reactions (6.1)].

17.6 Abnormal Thyroid FunctionAdvise patients that abnormal thyroid function may develop during INLYTA treatment

and to inform their doctor if symptoms of abnormal thyroid function occur [see Warningsand Precautions (5.7)].

17.7 Wound Healing ComplicationsAdvise patients to inform their doctor if they have an unhealed wound or if they have

surgery scheduled [see Warnings and Precautions (5.8)].17.8 Reversible Posterior Leukoencephalopathy SyndromeAdvise patients to inform their doctor if they have worsening of neurological function

consistent with RPLS (headache, seizure, lethargy, confusion, blindness and other visualand neurologic disturbances) [see Warnings and Precautions (5.9)].

17.9 PregnancyAdvise patients that INLYTA can cause birth defects or fetal loss and that they should

not become pregnant during treatment with INLYTA. Both male and female patients shouldbe counseled to use effective birth control during treatment with INLYTA. Female patientsshould also be advised against breast-feeding while receiving INLYTA [see Warnings andPrecautions (5.13) and Use in Specific Populations (8.3)].

17.10 Concomitant MedicationsAdvise patients to inform their doctor of all concomitant medications, vitamins, or

dietary and herbal supplements.This product’s label may have been updated. For current full prescribing information, pleasevisit www.pfizer.com.

LAB- 0561-3.0

PATIENT INFORMATIONINLYTA® (in-ly-ta)

(axitinib)tablets

Read this Patient Information before you start taking INLYTA and each timeyou get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or yourtreatment.What is INLYTA?INLYTA is a prescription medicine used to treat advanced kidney cancer (advanced renal cell carcinoma or RCC) when one prior drug treatment for thisdisease has not worked.It is not known if INLYTA is safe or effective in children.What should I tell my doctor before taking INLYTA?Before you take INLYTA, tell your doctor if you:• have high blood pressure• have thyroid problems• have liver problems• have a history of blood clots in your veins or arteries (types of blood vessels), including stroke, heart attack, or change in vision

• have any bleeding problems• have a history of heart failure• have an unhealed wound• plan to have surgery. You should stop taking INLYTA at least 24 hours before planned surgery.

• have any other medical conditionsFor females, tell your doctor if you:• are pregnant or plan to become pregnant. Taking INLYTA during pregnancy can cause the death of an unborn baby or birth defects. Youshould not become pregnant while taking INLYTA. Talk to your doctor ifyou are pregnant or plan to become pregnant.

• are able to become pregnant. You should use effective birth control during your treatment with INLYTA. Talk to your doctor about birth control methods to prevent pregnancy while you are taking INLYTA.

• are breastfeeding or plan to breastfeed. It is not known if INLYTA passesinto your breast milk. You and your doctor should decide if you will takeINLYTA or breastfeed. You should not do both.

For males:• use effective birth control during your treatment with INLYTA. Talk to yourdoctor about birth control methods.

• if your female partner becomes pregnant while you are taking INLYTA, tell your doctor right away.

Tell your doctor about all the medicines you take, including prescription andover-the-counter medicines, vitamins, and herbal supplements. INLYTA andcertain other medicines can affect each other causing serious side effects.Especially tell your doctor if you take:• dexamethasone• bosentan• modafinil• St. John’s wort (Hypericum perforatum)

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• Medicine for:• asthma• tuberculosis• seizures• bacterial infections• fungal infections• depression• HIV or AIDS

Ask your doctor or pharmacist if you are not sure if your medicine is one listedabove. If you are taking any medicines for the conditions listed above, your doctor might need to prescribe a different medicine or your dose of INLYTAmay need to be changed. Talk with your doctor before you start taking any newmedicine.Know the medicines you take. Keep a list of them to show your doctor andpharmacist when you get a new medicine.How should I take INLYTA?• Take INLYTA exactly as prescribed by your doctor.• Your doctor may change your dose if needed.• INLYTA can be taken with or without food.• Take INLYTA 2 times a day about 12 hours apart.• Swallow INLYTA tablets whole with a glass of water.• Your doctor should check your blood pressure regularly during treatmentwith INLYTA.

• If you vomit or miss a dose of INLYTA, take your next dose at your regular time. Do not take two doses at the same time.

• If you take too much INLYTA, call your doctor or go to the nearest hospital emergency room right away.

What should I avoid while taking INLYTA?• Do not drink grapefruit juice or eat grapefruit. Grapefruit may increase theamount of INLYTA in your blood.

What are the possible side effects of INLYTA?INLYTA may cause serious side effects, including:• High blood pressure (hypertension). Your doctor should check your bloodpressure regularly during treatment with INLYTA. If you develop bloodpressure problems, your doctor may prescribe medicine to treat your highblood pressure, lower your dose, or stop your treatment with INLYTA.

• Problem with blood clots in your veins or arteries. INLYTA can causeblood clots which can be serious, and sometimes lead to death. Get emer-gency help and call your doctor if you get any of the following symptoms:• chest pain or pressure• pain in your arms, back, neck or jaw• shortness of breath• numbness or weakness on one side of your body• trouble talking• headache• vision changes

• Bleeding. INLYTA can cause bleeding which can be serious, and sometimes lead to death. Call your doctor right away or get medical helpif you develop any of the following signs or symptoms:• unexpected bleeding or bleeding that lasts a long time, such as:

• unusual bleeding from the gums• menstrual bleeding or vaginal bleeding that is heavier than normal• bleeding that is severe or you cannot control• pink or brown urine• red or black stools (looks like tar)• bruises that happen without a known cause or get larger• cough up blood or blood clots• vomit blood or your vomit looks like “coffee grounds”

• unexpected pain, swelling, or joint pain• headaches, feeling dizzy or weak

• Heart failure. Your doctor should check for signs or symptoms of heartfailure regularly during treatment with INLYTA. Heart failure can be serious and can sometimes lead to death. Tell your doctor if you haveany of the following symptoms during your treatment with INLYTA:• tiredness• swelling of your stomach-area (abdomen), legs or ankles• shortness of breath• protruding neck veins

• Tear in your stomach or intestinal wall (perforation). A tear in your stomach or intestinal wall can be serious and can sometimes lead to death.Get medical help right away if you get the following symptoms:• severe stomach (abdominal) pain or stomach pain that does not go away• vomit blood• red or black stools

• Thyroid gland problems. Your doctor should do blood tests to check yourthyroid gland function before and during your treatment with INLYTA. Tell your doctor if you have any of the following symptoms during yourtreatment with INLYTA:• tiredness that worsens or that does not go away• feeling hot or cold• your voice deepens• weight gain or weight loss• hair loss• muscle cramps and aches

• Reversible Posterior Leukoencephalopathy Syndrome (RPLS). A conditioncalled reversible posterior leukoencephalopathy syndrome (RPLS) canhappen while taking INLYTA. Call your doctor right away if you get:• headache• seizures• weakness• confusion• high blood pressure• blindness or change in vision• problems thinking

• Increased protein in your urine. Your doctor should check your urine forprotein before and during your treatment with INLYTA. If you develop protein in your urine, your doctor may decrease your dose of INLYTA or stopyour treatment.

• Change in liver function. Your doctor should do blood tests before and during your treatment with INLYTA to check your liver function.

The most common side effects of INLYTA include:• diarrhea (frequent or loose bowel movements)• high blood pressure• tiredness or feeling weak• decreased appetite• nausea• hoarseness• rash, redness, itching or peeling of your skin on your hands and feet• decreased weight• vomiting• constipation

Tell your doctor if you have any side effect that bothers you or that does not goaway.These are not all the possible side effects of INLYTA. For more information, askyour doctor or pharmacist.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.How should I store INLYTA?• Store INLYTA at room temperature between 68oF to 77oF (20oC to 25oC).

Keep INLYTA and all medicines out of the reach of children.General information about INLYTA.Medicines are sometimes prescribed for purposes other than those listed in aPatient Information leaflet. Do not use INLYTA for a condition for which it wasnot prescribed. Do not give INLYTA to other people, even if they have the samesymptoms you have. It may harm them.This Patient Information leaflet summarizes the most important informationabout INLYTA. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about INLYTA that iswritten for health professionals.For more information, go to www.inlyta.com or call 877-744-5675.What are the ingredients in INLYTA?Active ingredient: axitinibInactive ingredients: microcrystalline cellulose, lactose monohydrate,croscarmellose sodium, magnesium stearate, and Opadry® II red 32K15441.The Opadry II red 32K15441 film coating contains: lactose monohydrate,HPMC 2910/Hypromellose 15cP, titanium dioxide, triacetin (glycerol triacetate),and red iron oxide.This Patient Information has been approved by the U.S. Food and Drug Administration.This product’s label may have been updated. For current full prescribing information, please visit www.pfizer.com.

LAB-0439-3.0Revised: 08/2014

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