NDC 63539-026 Inlyta

Axitinib

NDC Product Code 63539-026

NDC CODE: 63539-026

Proprietary Name: Inlyta What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Axitinib What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • This medication is used to treat kidney cancer after previous treatment has not been effective. Axitinib works by slowing or stopping the growth of cancer cells. It belongs to a class of drugs known as tyrosine kinase inhibitors.

Product Characteristics

Color(s):
RED (C48326)
Shape: TRIANGLE (C48353)
OVAL (C48345)
Size(s):
8 MM
Imprint(s):
PFIZER;5;XNB
PFIZER;1;XNB
Score: 1

NDC Code Structure

  • 63539 - U.s. Pharmaceuticals

NDC 63539-026-01

Package Description: 90 TABLET, FILM COATED in 1 BOTTLE

NDC Product Information

Inlyta with NDC 63539-026 is a a human prescription drug product labeled by U.s. Pharmaceuticals. The generic name of Inlyta is axitinib. The product's dosage form is tablet, film coated and is administered via oral form.

Labeler Name: U.s. Pharmaceuticals

Dosage Form: Tablet, Film Coated - A solid dosage form that contains medicinal substances with or without suitable diluents and is coated with a thin layer of a water-insoluble or water-soluble polymer.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Inlyta Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • AXITINIB 1 mg/1

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)
  • LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)
  • CROSCARMELLOSE SODIUM (UNII: M28OL1HH48)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
  • TRIACETIN (UNII: XHX3C3X673)
  • FERRIC OXIDE RED (UNII: 1K09F3G675)
  • HYPROMELLOSE 2910 (15000 MPA.S) (UNII: 288VBX44JC)
  • CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)
  • LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)
  • CROSCARMELLOSE SODIUM (UNII: M28OL1HH48)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
  • TRIACETIN (UNII: XHX3C3X673)
  • FERRIC OXIDE RED (UNII: 1K09F3G675)
  • HYPROMELLOSE 2910 (15000 MPA.S) (UNII: 288VBX44JC)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.
  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Kinase Inhibitor - [EPC] (Established Pharmacologic Class)
  • Receptor Tyrosine Kinase Inhibitors - [MoA] (Mechanism of Action)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: U.s. Pharmaceuticals
Labeler Code: 63539
FDA Application Number: NDA202324 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: NDA - A product marketed under an approved New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 01-27-2012 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2020 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Information for Patients

Axitinib

Axitinib is pronounced as (ax i' ti nib)

Why is axitinib medication prescribed?
Axitinib is used to treat advanced renal cell carcinoma (RCC, a type of cancer that begins in the cells of the kidneys) in people who have not been treated successfully w...
[Read More]

* Please review the disclaimer below.

Inlyta Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

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

The 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. The next prescribed dose should be taken at the usual time.

2.2 Dose Modification Guidelines

Dose 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 for Adverse 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 is recommended, the INLYTA dose may be increased to 7 mg twice daily, and further to 10 mg twice 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 reduction is required, the recommended dose is 2 mg twice daily.

Other

Strong CYP3A4/5 Inhibitors: The concomitant use of strong CYP3A4/5 inhibitors should be avoided (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole). Selection of an alternate concomitant medication with no or minimal CYP3A4/5 inhibition potential is recommended. Although INLYTA dose adjustment has not been studied in patients receiving strong CYP3A4/5 inhibitors, if a strong CYP3A4/5 inhibitor must be co-administered, a dose decrease of INLYTA by approximately half is recommended, as this dose reduction is predicted 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 pharmacokinetic data, the INLYTA starting dose should be reduced by approximately half in patients with baseline moderate hepatic impairment (Child-Pugh class B). The subsequent doses can be increased or decreased based on individual safety and tolerability. INLYTA has not been studied in patients with severe hepatic impairment (Child-Pugh class C) [see Warnings and Precautions (5.12), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].

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 steady state, axitinib exhibits approximately linear pharmacokinetics within the 1-mg to 20-mg dose 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 meal resulted 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 binding to albumin and moderate binding to α1-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/h and 160 (105%) L, respectively.

Metabolism and Elimination: The plasma half life of INLYTA ranges from 2.5 to 6.1 hours. Axitinib is metabolized primarily in the liver by CYP3A4/5 and to a lesser extent by CYP1A2, CYP2C19, and UGT1A1. Following oral administration of a 5-mg radioactive dose of axitinib, approximately 41% of the radioactivity was recovered in feces and approximately 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 in urine. In plasma, the N-glucuronide metabolite represented the predominant radioactive component (50% of circulating radioactivity) and unchanged axitinib and the sulfoxide metabolite 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 Interactions

Effects 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 pH resulting in lower solubility. The effects of a strong CYP3A4/5 inhibitor, a strong CYP3A4/5 inducer, and an antacid on the pharmacokinetics of axitinib are presented in Figure 1 [see Dosage 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 vitro studies in human hepatocytes indicated that axitinib does not induce CYP1A1, CYP1A2, or CYP3A4/5.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 Populations

Pediatric 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 severe renal 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 are available [see Use in Specific Populations (8.7)].

Other Intrinsic Factors: Population pharmacokinetic analyses indicate that there are no clinically relevant effects of age, gender, race, body weight, body surface area, UGT1A1 genotype, or CYP2C19 genotype on the clearance of axitinib.

This product's label may have been updated. For current full prescribing information, please visit www.pfizer.com.LAB- 0561-3.0

This product's label may have been updated. For current full prescribing information, please visit www.pfizer.com.LAB-0439-3.008/2014

3 Dosage Forms And Strengths

1 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 Contraindications

None

5.1 Hypertension And Hypertensive Crisis

In a controlled clinical study with INLYTA for the treatment of patients with RCC, hypertension 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 was reported in 2/359 patients (<1%) receiving INLYTA and none of the patients receiving sorafenib. The median onset time for hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg) was within the first month of the start of INLYTA treatment 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 should be 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 INLYTA is interrupted, patients receiving antihypertensive medications should be monitored for hypotension [see Dosage and Administration (2.2)].

5.2 Arterial Thromboembolic Events

In 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 and 4/355 patients (1%) receiving sorafenib. Fatal cerebrovascular accident was reported in 1/359 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 thromboembolic event within the previous 12 months.

5.3 Venous Thromboembolic Events

In clinical trials, venous thromboembolic events have been reported, including deaths. In a controlled clinical study with INLYTA for the treatment of patients with RCC, venous thromboembolic events were reported in 11/359 patients (3%) receiving INLYTA and 2/355 patients (1%) receiving sorafenib. Grade 3/4 venous thromboembolic events were reported in 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 deaths secondary 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 thromboembolic event within the previous 6 months.

5.4 Hemorrhage

In 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 64/355 patients (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 Failure

In 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%) receiving INLYTA and 1/355 patients (<1%) receiving sorafenib. Fatal cardiac failure was reported in 2/359 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 Formation

In a controlled clinical study with INLYTA for the treatment of patients with RCC, gastrointestinal perforation was reported in 1/359 patients (<1%) receiving INLYTA and none 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 cases of gastrointestinal perforation, fistulas were reported in 4/715 patients (1%).Monitor for symptoms of gastrointestinal perforation or fistula periodically throughout treatment with INLYTA.

5.7 Thyroid Dysfunction

In a controlled clinical study with INLYTA for the treatment of patients with RCC, hypothyroidism 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, treatment with INLYTA. Treat hypothyroidism and hyperthyroidism according to standard medical practice to maintain euthyroid state.

5.8 Wound Healing Complications

No 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 of adequate wound healing.

5.9 Reversible Posterior Leukoencephalopathy Syndrome

In 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 Reactions (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 hypertension may be present. Magnetic resonance imaging is necessary to confirm the diagnosis of RPLS. Discontinue INLYTA in patients developing RPLS. The safety of reinitiating INLYTA therapy in patients previously experiencing RPLS is not known.

5.10 Proteinuria

In 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, treatment with INLYTA is recommended. For patients who develop moderate to severe proteinuria, reduce the dose or temporarily interrupt INLYTA treatment.

5.11 Elevation Of Liver Enzymes

In 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 both arms, with Grade 3/4 events in <1% of patients on the INLYTA arm and 2% of patients on the sorafenib arm.Monitor ALT, aspartate aminotransferase (AST) and bilirubin before initiation of and periodically throughout treatment with INLYTA.

5.12 Hepatic Impairment

The systemic exposure to axitinib was higher in subjects with moderate hepatic impairment (Child-Pugh class B) compared to subjects with normal hepatic function. A dose 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), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].

5.13 Pregnancy

INLYTA 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 women using INLYTA. In developmental toxicity studies in mice, axitinib was teratogenic, embryotoxic and fetotoxic at maternal exposures that were lower than human exposures at the 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 pregnant while 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 reaction rates 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 Reactions (6.1)] reflect exposure to INLYTA in 359 patients with advanced RCC who participated in 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 healing complications, RPLS, proteinuria, elevation of liver enzymes, hepatic impairment and fetal development.

6.1 Clinical Trials Experience

The 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 reaction occurred in 199/359 patients (55%) receiving INLYTA and 220/355 patients (62%) receiving sorafenib. Permanent discontinuation due to an adverse reaction occurred in 34/359 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% patients who received INLYTA or sorafenib.Table 1. Adverse Reactions Occurring in ≥10% of Patients Who Received INLYTA or SorafenibAdverse ReactionPercentages are treatment-emergent, all-causality eventsINLYTA Sorafenib(N=359)(N=355)All GradesNational Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0Grade 3/4All GradesGrade 3/4%%%%Diarrhea5511537Hypertension40162911Fatigue3911325Decreased appetite345294Nausea323221Dysphonia310140Palmar-plantar erythrodysesthesia syndrome2755116Weight decreased252211Vomiting243171Asthenia215143Constipation201201Hypothyroidism19<180Cough151171Mucosal inflammation151121Arthralgia152111Stomatitis15112<1Dyspnea153123Abdominal pain142111Headache141110Pain in extremity131141Rash13<1324Proteinuria11372Dysgeusia11080Dry skin100110Dyspepsia10020Pruritus70120Alopecia40320Erythema2010<1Selected adverse reactions (all grades) that were reported in <10% of patients treated with 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 SorafenibLaboratory AbnormalityNINLYTANSorafenib All GradesNational Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0 Grade 3/4All GradesGrade 3/4%%%%ALP: alkaline phosphatase; ALT: alanine aminotransferase; AST: aspartate aminotransferaseHematologyHemoglobin decreased32035<1316524Lymphocytes (absolute) decreased317333309364Platelets decreased31215<1310140White blood cells decreased32011031516<1ChemistryCreatinine increased33655031841<1Bicarbonate decreased31444<1291430Hypocalcemia336391319592ALP increased336301319341Hyperglycemia336282319232Lipase increased3382753194615Amylase increased338252319332ALT increased33122<1313222AST increased33120<1311251Hypernatremia338171319131Hypoalbuminemia33715<1319181Hyperkalemia333153314103Hypoglycemia33611<13198<1Hyponatremia338134319112Hypophosphatemia3361323184916Selected laboratory abnormalities (all grades) that were reported in <10% of patients treated 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% for sorafenib).

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 Inhibitors

Co-administration of ketoconazole, a strong inhibitor of CYP3A4/5, increased the plasma exposure of axitinib in healthy volunteers. Co-administration of INLYTA with strong CYP3A4/5 inhibitors should be avoided. Grapefruit or grapefruit juice may also increase axitinib plasma concentrations and should be avoided. Selection of concomitant medication with no or minimal CYP3A4/5 inhibition potential is recommended. If a strong CYP3A4/5 inhibitor 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 Inducers

Co-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 with no 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 axitinib and should be avoided if possible.

Teratogenic Effects

Pregnancy 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 is used 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 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).

8.3 Nursing Mothers

It 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 or to discontinue the drug, taking into account the importance of the drug to the mother.

8.4 Pediatric Use

The 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 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.No dosage adjustment is required in elderly patients [see Dosage and Administration (2.2) and 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), and 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).

10 Overdosage

There 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 of 10 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 Description

INLYTA (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 is C22H18N4OS 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 axitinib in 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, croscarmellose sodium, magnesium stearate, and Opadry® II red 32K15441 as inactive ingredients. The Opadry II red 32K15441 film coating contains lactose monohydrate, HPMC 2910/Hypromellose 15cP, titanium dioxide, triacetin (glycerol triacetate), and red iron oxide.

12.1 Mechanism Of Action

Axitinib has been shown to inhibit receptor tyrosine kinases including vascular endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3 at therapeutic plasma concentrations. These receptors are implicated in pathologic angiogenesis, tumor growth, and cancer progression. VEGF-mediated endothelial cell proliferation and survival were inhibited by axitinib in vitro and in mouse models. Axitinib was shown to inhibit tumor growth and phosphorylation of VEGFR-2 in tumor xenograft mouse models.

12.2 Pharmacodynamics

The 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 Pharmacokinetics

The population pharmacokinetic analysis pooled data from 17 trials in healthy subjects and patients with cancer. A two-compartment disposition model with first-order absorption and lag-time adequately describes the axitinib concentration-time profile.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenicity 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 the testes/epididymis (decreased organ weight, atrophy or degeneration, decreased numbers of 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 AUC in patients at the recommended starting dose). Findings in the female reproductive tract in mice 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 and dogs, respectively).In a fertility study in mice, axitinib did not affect mating or fertility rate when administered orally twice daily to males at any dose tested up to 50 mg/kg/dose following at least 70 days of administration (approximately 57 times the AUC in patients at the recommended starting dose). In female mice, reduced fertility and embryonic viability were observed at all doses tested (≥15 mg/kg/dose administered orally twice daily) following at least 15 days of treatment with axitinib (approximately 10 times the AUC in patients at the recommended starting dose).

14 Clinical Studies

The 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 or interferon-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 and disease characteristics were similar between the INLYTA and sorafenib groups with regard to age (median 61 years), gender (72% male), race (75% white, 21% Asian), Eastern Cooperative Oncology 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 difference between the arms in OS.Table 3. Efficacy ResultsEndpoint/Study PopulationINLYTASorafenibHR (95% CI)P-valueCI: Confidence interval; HR: Hazard ratio (INLYTA/sorafenib); ITT: Intent to treat; ORR: Objective response rate; NS: Not significant; OS: Overall survival; PFS: Progression-free survivalOverall ITTN= 361N = 362Median PFSTime from randomization to progression or death due to any cause, whichever occurs first. ,Assessed by independent radiology review according to RECIST. in months (95% CI)6.7 (6.3, 8.6)4.7 (4.6, 5.6)0.67 (0.54, 0.81)<0.0001One-sided p-value from a log-rank test of treatment stratified by ECOG performance status and prior therapy (comparison is considered statistically significant if the one-sided p-value is <0.023). Median OS in months (95% CI)20.1 (16.7, 23.4)19.2 (17.5, 22.3)0.97 (0.80, 1.17)NSORR % (95% CI)19.4 (15.4, 23.9)9.4 (6.6, 12.9)2.06Risk 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. (1.41, 3.00)-P-value not included since it was not adjusted for multiple testing.PFS by prior treatmentSunitinib-refractory subgroupN=194N=195  Median, months (95% CI)4.8 (4.5, 6.4)3.4 (2.8, 4.7)0.74 (0.57, 0.96)-Cytokine-refractory subgroupN=126N=125  Median, months (95% CI)12.1 (10.1, 13.9)6.5 (6.3, 8.3)0.46 (0.32, 0.68)-Figure 2. Kaplan-Meier Curve for Progression Free Survival by Independent Assessment (Intent-to-Treat Population)

16 How Supplied/Storage And Handling

INLYTA tablets are supplied as follows: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 63539-044-01.

Storage And Handling

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 Hypertension

Advise 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 Events

Advise 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 Hemorrhage

Advise 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 Failure

Advise 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 Disorders

Advise 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 [see Warnings and Precautions (5.6) and Adverse Reactions (6.1)].

17.6 Abnormal Thyroid Function

Advise patients that abnormal thyroid function may develop during INLYTA treatment and to inform their doctor if symptoms of abnormal thyroid function occur [see Warnings and Precautions (5.7)].

17.7 Wound Healing Complications

Advise 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 Syndrome

Advise patients to inform their doctor if they have worsening of neurological function consistent with RPLS (headache, seizure, lethargy, confusion, blindness and other visual and neurologic disturbances) [see Warnings and Precautions (5.9)].

17.9 Pregnancy

Advise 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 should be counseled to use effective birth control during treatment with INLYTA. Female patients should also be advised against breast-feeding while receiving INLYTA [see Warnings and Precautions (5.13) and Use in Specific Populations (8.3)].

17.10 Concomitant Medications

Advise patients to inform their doctor of all concomitant medications, vitamins, or dietary and herbal supplements.

Patient Information

  • INLYTA® (in-ly-ta)(axitinib)tabletsRead this Patient Information before you start taking INLYTA and each time you 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 your treatment.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 this disease 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. 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.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 modafinil St. John's wort (Hypericum perforatum) Medicine for:asthmatuberculosis seizures bacterial infections fungal infections depressionHIV or AIDSAsk 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.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 treatment with 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 the amount 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 blood pressure regularly during treatment 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.Problem with 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 doctor if you get any of the following symptoms:chest pain or pressurepain in your arms, back, neck or jawshortness of breathnumbness or weakness on one side of your bodytrouble talkingheadachevision changesBleeding. 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 gumsmenstrual bleeding or vaginal bleeding that is heavier than normalbleeding that is severe or you cannot controlpink or brown urinered or black stools (looks like tar)bruises that happen without a known cause or get largercough up blood or blood clotsvomit blood or your vomit looks like "coffee grounds"unexpected pain, swelling, or joint painheadaches, feeling dizzy or weakHeart 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: tirednessswelling of your stomach-area (abdomen), legs or anklesshortness of breathprotruding neck veinsTear 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 awayvomit bloodred 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 awayfeeling hot or coldyour voice deepensweight gain or weight losshair lossmuscle cramps and achesReversible 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:headacheseizuresweaknessconfusionhigh blood pressureblindness or change in vision problems thinking 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 decreased appetite nausea hoarseness rash, redness, itching or peeling of your skin on your hands and feet decreased weight vomiting constipationTell 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.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 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.This Patient Information leaflet summarizes the most important information about INLYTA. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about INLYTA that is written 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.

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