Inlyta

Drug overview for INLYTA (axitinib):

Generic name: AXITINIB (ax-I-ti-nib)
Drug class: Antineoplastic - Protein-Tyrosine Kinase Inhibitors
Therapeutic class: Antineoplastics

Axitinib is a second-generation tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3; the drug is an antineoplastic agent.

No enhanced Uses information available for this drug.

DRUG IMAGES

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The following indications for INLYTA (axitinib) have been approved by the FDA:

Indications:
Renal cell carcinoma

Professional Synonyms:
Carcinoma of kidney
Grawitz tumor
Hypernephroid carcinoma
Hypernephroma
Kidney adenocarcinoma
Nephroid carcinoma
Renal adenocarcinoma
Renal carcinoma
Renal cell adenocarcinoma

The following dosing information is available for INLYTA (axitinib):

Dosing
Administration
INLYTA
Generic

Adjustment of axitinib dosage is recommended based on individual safety and tolerability. Recommended dosage reductions for adverse reactions are provided in Table 1.

Table 1: Recommended Dosage Reductions for Axitinib Toxicity.

Dosage Reduction Level Recommended Dosage First dose reduction 3 mg twice daily Second dose reduction 2 mg twice daily

Axitinib is administered orally twice daily (in doses given approximately 12 hours apart). The drug may be given without regard to meals. Axitinib tablets should be swallowed whole with a full glass of water; the tablets should not be crushed or split.

If a dose of axitinib is missed or vomited, patients should not double the dosage or take extra doses. The next dose should be taken at the regularly scheduled time. For patients unable to swallow tablets in clinical trials, axitinib tablets have been dissolved (without crushing) in 15 mL of USP-grade water in an amber-colored syringe and administered through a nasogastric tube; use of tap or bottled water was avoided.

The nasogastric tube should be flushed with 15 mL of USP-grade water prior to and following administration of the dose. The prepared dose should not be exposed to direct light and should be prepared just prior to administration. Procedures for proper handling of antineoplastic drugs should be followed when preparing doses of axitinib for nasogastric administration. Store axitinib tablets at 20-25oC; excursions permitted between 15-30oC.

Dosing information for INLYTA
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
INLYTA 5 MG TABLET	Maintenance	Adults take 1 tablet (5 mg) by oral route every 12 hours with a full glass (8 oz) water

No generic dosing information available.

The following drug interaction information is available for INLYTA (axitinib):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 3 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Axitinib/Strong CYP3A4 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Agents that inhibit the CYP3A4 isoenzyme may inhibit the metabolism of axitinib.(1) CLINICAL EFFECTS: Concurrent use of strong CYP3A4 inhibitors may increase levels of and effects from axitinib, including hypertension, thromboembolic events, or hepatotoxicity.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid the use of strong CYP3A4 inhibitors in patients undergoing therapy with axitinib.(1) Consider alternatives with no or minimal enzyme inhibition. If concurrent use with axitinib is warranted, consider decreasing the dose of axitinib by one-half (e.g. start with an initial dose of 2 mg twice daily). Subsequent doses may be increased or decreased based on patient response. When the CYP3A4 inhibitor has been discontinued, allow a washout period equal to 3-5 half-lives of the inhibitor before increasing the dose of axitinib.(1) DISCUSSION: Ketoconazole (400 mg twice daily, a strong inhibitor of CYP3A4) increased the maximum concentration (Cmax) and area-under-curve (AUC) of axitinib (5 mg) by approximately 1.5-fold and 2-fold, respectively. Recommended dosage adjustments are expected to produce AUC levels comparable to axitinib administered without a strong CYP3A4 inhibitor; however, no data is available.(1) Strong inhibitors of CYP3A4 include: adagrasib, boceprevir, ceritinib, clarithromycin, cobicistat, idelalisib, indinavir, itraconazole, josamycin, ketoconazole, lonafarnib, lopinavir, mibefradil, mifepristone, nefazodone, nelfinavir, nirmatrelvir/ritonavir, paritaprevir, posaconazole, ribociclib, saquinavir, telaprevir, telithromycin, tipranavir, troleandomycin, tucatinib, or voriconazole.(2,3)	APTIVUS, CLARITHROMYCIN, CLARITHROMYCIN ER, EVOTAZ, GENVOYA, ITRACONAZOLE, ITRACONAZOLE MICRONIZED, KALETRA, KETOCONAZOLE, KISQALI, KORLYM, KRAZATI, LANSOPRAZOL-AMOXICIL-CLARITHRO, LOPINAVIR-RITONAVIR, MIFEPREX, MIFEPRISTONE, NEFAZODONE HCL, NOXAFIL, OMECLAMOX-PAK, PAXLOVID, POSACONAZOLE, PREZCOBIX, RECORLEV, SPORANOX, STRIBILD, SYMTUZA, TOLSURA, TUKYSA, TYBOST, VFEND, VFEND IV, VIRACEPT, VOQUEZNA TRIPLE PAK, VORICONAZOLE, ZOKINVY, ZYDELIG, ZYKADIA
Sodium Iodide I 131/Myelosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1) DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1)	HICON, SODIUM IODIDE I-131
Axitinib/Strong & Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Agents that induce the CYP3A4 isoenzyme may induce the metabolism of axitinib.(1) CLINICAL EFFECTS: Concurrent use of strong or moderate CYP3A4 inducers may decrease the levels and effectiveness of axitinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid the concurrent use of strong or moderate CYP3A4 inducers in patients receiving therapy with axitinib.(1) Consider the use of alternatives with little to no induction potential.(1) DISCUSSION: Rifampin (600 mg daily for 9 days), a strong CYP3A4 inducer, decreased the maximum concentration (Cmax) and area-under-curve (AUC) of axitinib to less than half and less than 25% of levels seen without concurrent rifampin.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, dexamethasone, encorafenib, enzalutamide, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentine, and St. John's wort. Moderate inducers of CYP3A4 include: bosentan, cenobamate, dabrafenib, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, sotorasib, telotristat ethyl, thioridazine and tovorafenib.(1-3)	ASA-BUTALB-CAFFEINE-CODEINE, ASCOMP WITH CODEINE, AUGTYRO, BOSENTAN, BRAFTOVI, BUPIVACAINE-DEXAMETH-EPINEPHRN, BUTALB-ACETAMINOPH-CAFF-CODEIN, BUTALBITAL, BUTALBITAL-ACETAMINOPHEN, BUTALBITAL-ACETAMINOPHEN-CAFFE, BUTALBITAL-ASPIRIN-CAFFEINE, CAMZYOS, CARBAMAZEPINE, CARBAMAZEPINE ER, CARBATROL, CEREBYX, DEXABLISS, DEXAMETHASONE, DEXAMETHASONE ACETATE, DEXAMETHASONE ACETATE MICRO, DEXAMETHASONE INTENSOL, DEXAMETHASONE ISONICOTINATE, DEXAMETHASONE MICRONIZED, DEXAMETHASONE SOD PHOS-WATER, DEXAMETHASONE SODIUM PHOSPHATE, DEXAMETHASONE-0.9% NACL, DILANTIN, DILANTIN-125, DMT SUIK, DONNATAL, DOUBLEDEX, DUZALLO, EFAVIRENZ, EFAVIRENZ-EMTRIC-TENOFOV DISOP, EFAVIRENZ-LAMIVU-TENOFOV DISOP, EPITOL, EQUETRO, ERLEADA, ETRAVIRINE, FIORICET, FIORICET WITH CODEINE, FOSPHENYTOIN SODIUM, HEMADY, INTELENCE, LIDOCIDEX-I, LORBRENA, LUMAKRAS, LYSODREN, MAS CARE-PAK, MITOTANE, MODAFINIL, MYSOLINE, NAFCILLIN, NAFCILLIN SODIUM, OJEMDA, ORIAHNN, ORILISSA, ORKAMBI, PENTOBARBITAL SODIUM, PHENOBARBITAL, PHENOBARBITAL SODIUM, PHENOBARBITAL-BELLADONNA, PHENOBARBITAL-HYOSC-ATROP-SCOP, PHENOHYTRO, PHENYTEK, PHENYTOIN, PHENYTOIN SODIUM, PHENYTOIN SODIUM EXTENDED, PRIFTIN, PRIMIDONE, PROVIGIL, PYRUKYND, RIFABUTIN, RIFADIN, RIFAMPIN, SEZABY, SYMFI, SYMFI LO, TAFINLAR, TALICIA, TAPERDEX, TEGRETOL, TEGRETOL XR, TENCON, THIORIDAZINE HCL, THIORIDAZINE HYDROCHLORIDE, TIBSOVO, TRACLEER, TURALIO, VONJO, XCOPRI, XERMELO, XTANDI, ZCORT

There are 0 moderate interactions.

The following contraindication information is available for INLYTA (axitinib):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

None.

There are 3 contraindications. Absolute contraindication.

Contraindication List
Arterial aneurysm
Arterial dissection
Lactation

There are 18 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Acute myocardial infarction
Cerebral metastases
Cerebrovascular accident
Child-pugh class B hepatic impairment
Chronic heart failure
Deep venous thrombosis
Disease of liver
Gastrointestinal hemorrhage
Hypertension
Impaired wound healing
Intracerebral hemorrhage
Posterior reversible encephalopathy syndrome
Pregnancy
Proteinuria
Pulmonary thromboembolism
Retinal vascular occlusion
Thromboembolic disorder
Transient cerebral ischemia

There are 3 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Gastrointestinal fistula
Gastrointestinal perforation
Hypothyroidism

The following adverse reaction information is available for INLYTA (axitinib):

Overview
Severe
Less Severe

Adverse reaction overview.

Adverse effects occurring in 20% or more of patients receiving axitinib in combination with avelumab for first-line treatment of advanced renal cell carcinoma were diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia (hand-foot syndrome), dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain, and headache. Adverse effects occurring in 20% or more of patients receiving axitinib in combination with pembrolizumab for first-line treatment of advanced renal cell carcinoma were diarrhea, fatigue/asthenia, hypertension, hypothyroidism, decreased appetite, hepatotoxicity, palmar-plantar erythrodysesthesia (hand-foot syndrome), nausea, stomatitis/mucosal inflammation, dysphonia, rash, cough, and constipation. Adverse effects occurring in 20% or more of patients receiving axitinib for the second-line treatment of advanced renal cell carcinoma in the randomized trial were diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, palmar-plantar erythrodysesthesia (hand-foot syndrome), weight loss, vomiting, asthenia, and constipation.

There are 33 severe adverse reactions.

More Frequent	Less Frequent
Hemorrhage Hypertension Hypothyroidism Increased alanine transaminase Increased aspartate transaminase Leukopenia Lymphopenia Thrombocytopenic disorder	Acute myocardial infarction Anemia Arterial thrombosis Deep venous thrombosis Heart failure Hemoptysis Hyperbilirubinemia Hypercalcemia Hyperthyroidism Pulmonary thromboembolism Rectal bleeding Retinal thrombosis Thromboembolic disorder Thrombotic disorder

Rare/Very Rare
Abnormal hepatic function tests Arterial aneurysm Arterial dissection Gastrointestinal fistula Gastrointestinal perforation Hepatic failure Hypertensive crisis Impaired wound healing Intracerebral hemorrhage Posterior reversible encephalopathy syndrome Transient cerebral ischemia

There are 32 less severe adverse reactions.

More Frequent	Less Frequent
Acute abdominal pain Anorexia Arthralgia Constipation Cough Dehydration Diarrhea Dizziness Dry skin Dysgeusia Dyspepsia Dyspnea Epistaxis Fatigue General weakness Headache disorder Myalgia Nausea Palmar-plantar erythrodysesthesia Proteinuria Pruritus of skin Skin rash Stomatitis Voice change Vomiting Weight loss	Alopecia Elevated serum lipase Erythema Erythrocytosis Hemorrhoids Sore tongue

Rare/Very Rare
None.

The following precautions are available for INLYTA (axitinib):

Pediatric
Pregnant
Lactation
Geriatric

Safety and efficacy of axitinib have not been established in pediatric patients younger than 18 years of age. The pharmacokinetics of axitinib also have not been studied in pediatric patients. Toxicities in bone (e.g., thickened growth plates) and teeth (e.g., abnormalities in growing incisor teeth, including dental caries, malocclusions, broken and/or missing teeth) have been observed in immature animals receiving oral axitinib for one month or longer. Other toxicities of potential concern in pediatric patients have not been evaluated to date in juvenile animal studies.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Axitinib may cause fetal harm if administered to pregnant women based on its mechanism of action and animal findings. There are no available human data to inform the drug-associated risk.

It is not known whether axitinib is distributed into human milk. The effects of the drug on breast-fed infants or on the production of milk are unknown. Because of the potential for adverse reactions to axitinib in breast-fed infants, females should be advised not to breast-feed while receiving the drug and for 2 weeks after the last dose.

No dosage adjustment is necessary in geriatric patients. In controlled clinical studies evaluating axitinib in patients with renal cell carcinoma either as a single agent or in combination with avelumab or pembrolizumab, 34-40% of patients were 65 years of age or older. Although no overall differences in safety and efficacy were observed between patients 65 years of age or older and younger patients, the possibility of increased sensitivity to the drug in some geriatric patients cannot be ruled out.

Renal cell carcinoma
C64	Malignant neoplasm of kidney, except renal pelvis
C64.1	Malignant neoplasm of right kidney, except renal pelvis
C64.2	Malignant neoplasm of left kidney, except renal pelvis
C64.9	Malignant neoplasm of unspecified kidney, except renal pelvis