(axitinib)

Prescribing Information
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8 USE IN SPECIFIC POPULATIONS

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Based on findings in animal studies and its mechanism of action, INLYTA can cause fetal harm when administered to a pregnant woman. There are no available human data to inform the drug-associated risk. In developmental toxicity studies, axitinib was teratogenic, embryotoxic and fetotoxic in mice at exposures lower than human exposures at the recommended starting dose (see Data). Advise females of reproductive potential of the potential risk to a fetus.

The background risk of major birth defects and miscarriage for the indicated populations are unknown. However, the background risk in the United States (U.S.) general population of major birth defects is 2%–4% and of miscarriage is 15%–20% of clinically recognized pregnancies.

When INLYTA is used in combination with avelumab or pembrolizumab, refer to the full prescribing information of avelumab or pembrolizumab for pregnancy information.

Data

Animal Data

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 the recommended starting dose). In an embryo-fetal developmental toxicity study, pregnant mice 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 times the AUC in patients at the recommended starting dose) and variation in skeletal ossification at ≥0.5 mg/kg/dose (approximately 0.15 times the AUC in patients at the recommended starting dose).

8.2 Lactation

Risk Summary

There are no data on the presence of axitinib in human milk, or its effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in a breastfed child from INLYTA, advise lactating women not to breastfeed during treatment and for 2 weeks after the last dose.

When INLYTA is used in combination with avelumab or pembrolizumab, refer to the full prescribing information of avelumab or pembrolizumab for lactation information.

8.3 Females and Males of Reproductive Potential

Based on findings in animal studies, INLYTA can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. When INLYTA is used in combination with avelumab or pembrolizumab, refer to the full prescribing information of avelumab or pembrolizumab for contraception information.

Pregnancy Testing

Verify pregnancy status in females of reproductive potential prior to initiating treatment with INLYTA.

Contraception

Females

Advise females of reproductive potential to use effective contraception during treatment with INLYTA and for 1 week after the last dose.

Males

Based on findings in animal studies, advise males with female partners of reproductive potential to use effective contraception during treatment and for 1 week after the last dose.

Infertility

Females and Males

Based on findings in animals, INLYTA may impair fertility in females and males of reproductive potential [see Nonclinical Toxicology (13.1)].

8.4 Pediatric Use

The safety and effectiveness of INLYTA in pediatric patients have not been established.

The safety and effectiveness of INLYTA were assessed, but not established, in two open label studies: a dose finding study of INLYTA as a single agent in 17 pediatric patients aged 5 to <17 years with recurrent or refractory solid tumors (ADVL1315, NCT02164838) and a randomized study of INLYTA as a single agent or in combination in 7 pediatric patients aged 7 to <17 years (AREN1721, NCT03595124).

No new safety signals were observed with INLYTA in pediatric patients across these studies.

Exposure in pediatric patients who received INLYTA at the maximum tolerated dosage were lower than those previously observed in adults who received the approved recommended starting dosage.

Juvenile Animal Toxicity Data

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 growth plates in mice and dogs at ≥15 mg/kg/dose (approximately 6 and 15 times, respectively, the systemic exposure (AUC) in patients at the recommended starting dose). Abnormalities in growing incisor teeth (including dental caries, malocclusions and broken and/or missing teeth) 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). Other toxicities of potential concern to pediatric patients have not been evaluated in juvenile animals.

8.5 Geriatric Use

In 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 in some older individuals cannot be ruled out, no overall differences were observed in the safety and effectiveness of INLYTA between patients who were ≥65 years of age and younger.

Of the 434 patients randomized to INLYTA 5 mg twice daily administered in combination with avelumab 10 mg/kg in the JAVELIN Renal 101 trial, 38% were 65 years or older and 8% were 75 years or older. No overall difference in safety or efficacy was reported between patients who were ≥65 years of age and younger.

Of the 432 patients randomized to INLYTA 5 mg twice daily administered in combination with pembrolizumab 200 mg in the KEYNOTE-426 trial, 40% were 65 years or older. No overall difference in safety or efficacy was reported between patients who were ≥65 years of age and younger.

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

8.6 Hepatic Impairment

In a dedicated hepatic impairment trial, compared to subjects with normal hepatic function, systemic exposure following a single dose of INLYTA was similar in subjects with baseline mild hepatic impairment (Child-Pugh class A) and higher in subjects with baseline moderate hepatic impairment (Child-Pugh class B).

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

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

8.7 Renal Impairment

No 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 starting dose 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).

Medication Guide

MEDICATION GUIDE

PATIENT INFORMATION
INLYTA® (in-ly-ta)
(axitinib)
tablets

Important information: If your healthcare provider prescribes INLYTA for you to be taken with avelumab or pembrolizumab, also read the Medication Guide for avelumab or pembrolizumab.

What is INLYTA?
INLYTA is a prescription medicine used to treat kidney cancer that has spread or cannot be removed by surgery (advanced renal cell carcinoma or RCC):

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in combination with avelumab or pembrolizumab as your first treatment.
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alone when 1 prior drug treatment regimen for your RCC has not worked.

It is not known if INLYTA is safe and effective in children.

Before taking INLYTA, tell your healthcare provider about all of your medical conditions, including if you:

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have high blood pressure
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have thyroid problems
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have liver problems
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have a history of blood clots in your veins or arteries (types of blood vessels), including stroke, heart attack, or change in vision
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have any bleeding problems
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have a history of heart problems, including heart failure
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have an unhealed wound
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plan to have surgery or have had a recent surgery. You should stop taking INLYTA for at least 2 days before planned surgery. See "What are the possible side effects of INLYTA?"

For females, tell your healthcare provider if you:

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are pregnant or plan to become pregnant. Taking INLYTA during pregnancy can harm your unborn baby. You should not become pregnant during treatment with INLYTA.
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are able to become pregnant. You should have a pregnancy test before you start treatment with INLYTA. Use effective birth control during treatment and for 1 week after your last dose of INLYTA. Talk to your healthcare provider about birth control methods that you can use to prevent pregnancy during this time.
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are breastfeeding or plan to breastfeed. It is not known if INLYTA passes into your breast milk. Do not breastfeed during treatment and for 2 weeks after your last dose of INLYTA.

For males with female partners who are able to become pregnant:

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Use effective birth control during treatment and for 1 week after your last dose of INLYTA.
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If your female partner becomes pregnant during your treatment with INLYTA, tell your healthcare provider right away.

Tell your healthcare provider 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 healthcare provider before you start taking any new medicine. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I take INLYTA?

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Take INLYTA exactly as prescribed by your healthcare provider.
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Your healthcare provider may change your dose if needed.
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INLYTA can be taken with or without food.
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Take INLYTA 2 times a day about 12 hours apart.
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Swallow INLYTA tablets whole with a glass of water.
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Your healthcare provider should check your blood pressure regularly during treatment with INLYTA.
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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.
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If you take too much INLYTA, call your healthcare provider or go to the nearest hospital emergency room right away.

What should I avoid while taking INLYTA?

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

What are the possible side effects of INLYTA?
INLYTA may cause serious side effects, including:

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High blood pressure (hypertension). High blood pressure is common with INLYTA and may sometimes be severe. Your healthcare provider should check your blood pressure regularly during treatment with INLYTA. If you develop blood pressure problems, your healthcare provider may prescribe medicine to treat your high blood pressure, lower your dose, or stop your treatment with INLYTA.
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Blood clots in your veins or arteries. INLYTA can cause blood clots which can be serious, and sometimes lead to death. Get emergency help and call your healthcare provider if you get any of the following symptoms:
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chest pain or pressure
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pain in your arms, back, neck or jaw
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shortness of breath
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numbness or weakness on one side of your body
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trouble talking
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headache
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vision changes
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Bleeding. INLYTA can cause bleeding which can be serious, and sometimes lead to death. Call your healthcare provider right away or get medical help if you develop any of the following signs or symptoms:
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unexpected bleeding or bleeding that lasts a long time, such as:
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unusual bleeding from the gums
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menstrual bleeding or vaginal bleeding that is heavier than normal
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bleeding that is severe or you cannot control
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pink or brown urine
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red or black stools (looks like tar)
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bruises that happen without a known cause or get larger
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cough up blood or blood clots
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vomit blood or your vomit looks like "coffee grounds"
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unexpected pain, swelling, or joint pain
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headaches, feeling dizzy or weak
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Heart failure. Your healthcare provider should check you 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 healthcare provider if you have any of the following symptoms during your treatment with INLYTA:
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tiredness
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swelling of your stomach-area (abdomen), legs or ankles
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shortness of breath
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protruding neck veins
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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:
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severe stomach-area (abdominal) pain or stomach-area pain that does not go away
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vomit blood
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red or black stools
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Thyroid gland problems. Your healthcare provider should do blood tests to check your thyroid gland function before and during your treatment with INLYTA. Tell your healthcare provider if you have any of the following symptoms during your treatment with INLYTA:
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tiredness that worsens or that does not go away
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feeling hot or cold
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your voice deepens
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weight gain or weight loss
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hair loss
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muscle cramps and aches
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Risk of wound healing problems. Wounds may not heal properly during INLYTA treatment. Tell your healthcare provider if you plan to have any surgery before starting or during treatment with INLYTA.
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You should stop taking INLYTA at least 2 days before planned surgery.
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Your healthcare provider should tell you when you may start taking INLYTA again after surgery.
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Reversible Posterior Leukoencephalopathy Syndrome (RPLS). A condition called reversible posterior leukoencephalopathy syndrome (RPLS) can happen during treatment with INLYTA. Call your healthcare provider right away if you get:
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headache
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seizures
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weakness
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confusion
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high blood pressure
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blindness or change in vision
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problems thinking
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Protein in your urine. Your healthcare provider should check your urine for protein before and during your treatment with INLYTA. If you develop protein in your urine, your healthcare provider may decrease your dose of INLYTA or stop your treatment.
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Liver problems. Your healthcare provider will do blood tests before and during your treatment with INLYTA. Your healthcare provider may delay or stop your treatment with INLYTA if you develop severe liver problems.
Tell your healthcare provider right way if you have any of the following symptoms:
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yellowing of your skin or the whites of your eyes
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severe nausea or vomiting
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pain on the right side of your stomach area (abdomen)
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dark urine (tea colored)
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bleeding or bruising more easily than normal
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Heart problems. When INLYTA is used with the medicine avelumab, severe heart problems can happen and can lead to death. Your healthcare provider will check you for heart problems during your treatment with INLYTA. Tell your healthcare provider right away or get medical help if you have any of the following symptoms:
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swelling of your stomach-area, legs, hands feet or ankles
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shortness of breath
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nausea or vomiting
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new or worsening chest discomfort, including pain or pressure
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weight gain
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pain or discomfort in your arms, back, neck, or jaw
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breaking out in a cold sweat
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feeling lightheaded or dizzy

The most common side effects of INLYTA with avelumab include:

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diarrhea
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feeling tired
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high blood pressure
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muscle and bone pain
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nausea
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mouth sores
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rash, redness, itching, or peeling of your skin on your hands and feet
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hoarseness
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decreased appetite
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low levels of thyroid hormone
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rash
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liver problems
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cough
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shortness of breath
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stomach-area (abdomen) pain
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headache

The most common side effects of INLYTA with pembrolizumab include:

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diarrhea
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feeling tired or weak
o
high blood pressure
o
liver problems
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low levels of thyroid hormone
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decreased appetite
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rash, redness, itching or peeling of your skin on your hands and feet
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nausea
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mouth sores or swelling of the lining of the mouth, nose, eyes, throat, intestines, or vagina
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hoarseness
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rash
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cough
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constipation

The most common side effects of INLYTA when used alone include:

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diarrhea
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high blood pressure
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feeling tired or weak
o
decreased appetite
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nausea
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hoarseness
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rash, redness, itching or peeling of your skin on your hands and feet
o
decreased weight
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vomiting
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constipation

INLYTA may cause fertility problems in males and females, which may affect your ability to have a child. Talk to your healthcare provider if this is a concern for you.
These are not all of the possible side effects of INLYTA.
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 68°F to 77°F (20°C to 25°C).

Keep INLYTA and all medicines out of the reach of children.

General information about the safe and effective use of INLYTA.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use INLYTA for a condition for which it was not prescribed. Do not give INLYTA to other people, even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for information about INLYTA that is written for health professionals.

What are the ingredients in INLYTA?
Active ingredient: axitinib
Inactive 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.

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LAB-0439-8.0

For more information, go to www.inlyta.com or call 877-0744-5675
This product's labeling may have been updated. For the most recent prescribing information, please visit www.pfizer.com.

This Patient Information has been approved by the U.S. Food and Drug Administration.     Revised: 07/2024

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