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Axitinib

Class: Antineoplastic Agents
- Kinase Inhibitors
- Receptor Tyrosine Kinase Inhibitors
- Tyrosine Kinase Inhibitors
- VEGF Receptor Inhibitors
- VEGFR Inhibitors
- Vascular Endothelial Growth Factor Receptor Inhibitors
VA Class: AN900
Chemical Name: N-Methyl-2-[[3-[(1E)-2-(2-pyridinyl)ethenyl]-1H-indazol-6-yl]thio]-benzamide
Molecular Formula: C22H18N4OS
CAS Number: 319460-85-0
Brands: Inlyta ([Web])

Medically reviewed by Drugs.com on Apr 6, 2022. Written by ASHP.

Introduction

Antineoplastic agent; a second-generation tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3.

Uses for Axitinib

Renal Cell Carcinoma

In combination with avelumab for the initial treatment of advanced renal cell carcinoma.

In combination with pembrolizumab for the initial treatment of advanced renal cell carcinoma.

Monotherapy for the treatment of advanced renal cell carcinoma following failure of one prior systemic therapy.

Has been used as monotherapy for the first-line treatment of metastatic renal cell carcinoma.

Other Uses

Has been used for the treatment of advanced thyroid cancer.

Axitinib Dosage and Administration

General

Pretreatment Screening

  • Assess baseline ALT, AST, and bilirubin concentrations.

  • Blood pressure should be adequately controlled prior to initiating therapy. Do not initiate in patients with uncontrolled hypertension.

  • Consider assessing left ventricular ejection fraction (LVEF) at baseline.

  • Perform thyroid function tests at baseline; treat hypothyroidism and hyperthyroidism according to standard medical practice to maintain a euthyroid state.

  • Assess for proteinuria.

  • Verify pregnancy status of females of reproductive potential prior to initiation of therapy.

Patient Monitoring

  • Monitor ALT, AST, and bilirubin concentrations periodically during therapy. When axitinib is used in combination with avelumab or pembrolizumab, consider more frequent monitoring.

  • Consider periodically monitoring LVEF.

  • Monitor for signs and symptoms of cardiac failure periodically during therapy.

  • Monitor for manifestations of GI perforation or fistula.

  • Monitor blood pressure regularly.

  • Monitor thyroid function periodically during therapy; treat hypothyroidism and hyperthyroidism according to standard medical practice to maintain a euthyroid state.

  • Monitor for proteinuria periodically during therapy.

Other General Considerations

  • Clinicians should consult published protocols for information on the dosage, method of administration, and administration sequence of other antineoplastic agents used in combination regimens with axitinib.

  • Withhold axitinib for ≥2 days prior to elective surgery and for ≥2 weeks following major surgery and until adequate wound healing occurs.

Administration

Oral Administration

Administer orally twice daily (in doses given approximately 12 hours apart) without regard to meals.

Swallow tablets whole with a full glass of water; do not crush or split.

If a dose is missed or vomited, do not double the dosage or take extra doses. Take the next dose at the regularly scheduled time.

NG Tube

Prepare each dose just prior to administration.

In clinical trials, axitinib has been given by NG tube after dissolving the tablets (without crushing) in 15 mL of USP-grade water in an amber-colored syringe; use of tap or bottled water was avoided. The NG tube was flushed with USP-grade water prior to and following administration of the dose. Do not expose prepared NG dose to direct light.

Avoid contact of prepared dose with skin or mucous membranes. If such contact occurs, flush affected area with water.

Dosage

Adults

Renal Cell Carcinoma
First-line Therapy: Combination Therapy with Avelumab
Oral

Initially, 5 mg twice daily in combination with avelumab IV (800 mg every 2 weeks). In principal efficacy study, therapy was continued until disease progression or unacceptable toxicity occurred; median duration of axitinib was 9 months.

In patients who tolerate initial dosage for at least 2 consecutive weeks (no adverse effects greater than grade 2, normotensive, no antihypertensive use), may increase dosage to 7 mg twice daily, and then may increase further to 10 mg twice daily using the same criteria.

Manufacturer recommends reducing initial dosage by approximately 50% if concomitant use of a potent CYP3A4/5 inhibitor is required; may increase or decrease subsequent dosages based on individual safety and tolerability.

First-line Therapy: Combination Therapy with Pembrolizumab
Oral

Initially, 5 mg twice daily in combination with pembrolizumab IV (200 mg every 3 weeks or 400 mg every 6 weeks). In principal efficacy study, therapy was continued until disease progression or unacceptable toxicity occurred; median duration of axitinib was 10.4 months.

In patients who tolerate initial dosage for at least 2 consecutive weeks (no adverse effects greater than grade 2, normotensive, no antihypertensive use), may increase dosage to 7 mg twice daily, and then may increase further to 10 mg twice daily using the same criteria.

Manufacturer recommends reducing initial dosage by approximately 50% if concomitant use of a potent CYP3A4/5 inhibitor is required; may increase or decrease subsequent dosages based on individual safety and tolerability.

Second-line Therapy: Monotherapy
Oral

Initially, 5 mg twice daily. In principal efficacy study, therapy was continued until disease progression or unacceptable toxicity occurred; median duration of therapy was 6.4 months.

In patients who tolerate initial dosage for at least 2 consecutive weeks (no adverse effects greater than grade 2, normotensive, no antihypertensive use), may increase dosage to 7 mg twice daily, and then may increase further to 10 mg twice daily using the same criteria.

Manufacturer recommends reducing initial dosage by approximately 50% if concomitant use of a potent CYP3A4/5 inhibitor is required; may increase or decrease subsequent dosages based on individual safety and tolerability.

Dosage Modification for Toxicity
Oral

Adjust dosage based on individual safety and tolerability.

Some adverse effects require temporary interruption, permanent discontinuance, and/or dosage reduction. If dosage reduction from 5 mg twice daily is necessary, recommended dosage is 3 mg twice daily. If further dosage reduction is required, recommended dosage is 2 mg twice daily.

Hepatotoxicity
Oral

Combination therapy with avelumab: If elevations in ALT or AST concentrations 3 times the ULN, but ≤ times the ULN or total bilirubin concentration 1.5–3 times the ULN occur, withhold both axitinib and avelumab until hepatotoxicity resolves to grade 1 or less. If these elevations persist for >5 days, consider corticosteroid therapy (initial dose of 0.5–1 mg/kg per day of prednisone [or equivalent]) followed by tapering of the corticosteroid dosage. Consider rechallenging with a single drug or sequential rechallenge with both drugs following recovery. If rechallenging with axitinib, consider reducing the dosage of axitinib. If ALT or AST concentrations increase to 5 times the ULN or >3 times the ULN with concurrent total bilirubin concentrations >2 times the ULN or total bilirubin concentration ≥3 times the ULN, permanently discontinue both axitinib and avelumab and consider corticosteroid therapy (initial dose 1 to 2 mg/kg per day prednisone [or equivalent]) followed by tapering of the corticosteroid dosage.

Combination therapy with pembrolizumab: If elevations in ALT or AST concentrations 3–10 times the ULN occur without concurrent elevations of total bilirubin concentrations to 2 times the ULN, withhold both axitinib and pembrolizumab until hepatotoxicity resolves to grade 1 or less, and consider corticosteroid therapy. Consider rechallenging with a single drug or sequential rechallenge with both drugs after recovery. If rechallenging with axitinib, consider reducing the dosage of axitinib. If ALT or AST increase to ≥10 times ULN or exceed 3 times the ULN with concurrent elevations in total bilirubin concentration to ≥2 times ULN, permanently discontinue both axitinib and pembrolizumab and consider corticosteroid therapy.

Special Populations

Hepatic Impairment

Mild preexisting hepatic impairment (Child-Pugh class A): No initial dosage adjustment required.

Moderate preexisting hepatic impairment (Child-Pugh class B): Reduce initial dosage by approximately 50% (i.e., to 2.5 mg twice daily); may increase or decrease subsequent dosages based on individual safety and tolerability.

Severe hepatic impairment (Child-Pugh class C): Not studied. (See Hepatic Impairment under Cautions.)

Renal Impairment

Mild to severe preexisting renal impairment (Clcr 15–89 mL/minute): No initial dosage adjustment required.

End-stage renal disease (Clcr <15 mL/minute): Use with caution. (See Renal Impairment under Cautions.)

Geriatric Patients

No dosage adjustment required.

Cautions for Axitinib

Contraindications

  • Manufacturer states none known.

Warnings/Precautions

Hypertension and Hypertensive Crisis

Hypertension and hypertensive crisis reported in 40% (grade 3 or 4 in 16%) and <1% of axitinib-treated patients, respectively, in the primary efficacy study. Median time to onset of hypertension is within the first month; BP increases have been observed as early as 4 days after initiating therapy.

Control BP well prior to initiating axitinib therapy. Monitor for hypertension during therapy and treat as needed with standard antihypertensive therapy. If hypertension persists despite antihypertensive therapy, reduce axitinib dosage. Discontinue axitinib if severe and persistent hypertension occurs despite dosage reduction and antihypertensive therapy. Consider discontinuance of drug if there is evidence of hypertensive crisis. Monitor for hypotension if axitinib therapy is interrupted and antihypertensive therapy is continued.

Arterial Thromboembolic Events

Arterial thromboembolic events (e.g., TIA, cerebrovascular accident, MI, retinal artery occlusion), including fatal cases, reported.

Use with caution in patients who are at risk for, or have a history of, arterial thromboembolic events. Not evaluated in patients who had an arterial thromboembolic event within the past 12 months.

Venous Thromboembolic Events

Venous thromboembolic events (e.g., pulmonary embolism, DVT, retinal vein occlusion, retinal vein thrombosis), including fatal cases, reported.

Use with caution in patients who are at risk for, or have a history of, venous thromboembolic events. Not evaluated in patients who had a venous thromboembolic event within the past 6 months.

Hemorrhage

Hemorrhagic events, including fatal cases, reported. Grade 3 or 4 hemorrhagic events have included cerebral hemorrhage, hematuria, hemoptysis, lower GI hemorrhage, and melena.

Not evaluated in patients with evidence of untreated brain metastasis or recent, active GI bleeding; avoid use in such patients. Temporarily interrupt therapy if any bleeding requires medical intervention.

Cardiac Failure

Cardiac failure, including fatal cases, reported.

Monitor for signs or symptoms of cardiac failure. Permanent discontinuance of axitinib may be necessary.

GI Perforation and Fistula Formation

GI perforation (including one death) and fistula formation reported in axitinib-treated patients in clinical trials.

Use with caution in patients at risk for GI perforation or fistula. Monitor for symptoms of GI perforation or fistula formation periodically during treatment.

Thyroid Dysfunction

Thyroid dysfunction (hypothyroidism or hyperthyroidism) requiring thyroid hormone replacement therapy reported with certain tyrosine kinase inhibitors, including axitinib.

Assess baseline thyroid function prior to initiation of therapy and then monitor periodically during treatment. Treat hypothyroidism and hyperthyroidism according to standard medical practice to maintain a euthyroid state.

Wound Healing Complications

VEGFR inhibitors, such as axitinib, may impair wound healing.

Discontinue axitinib ≥2 days prior to elective surgery and for ≥2 weeks following major surgery. Decision to resume therapy postoperatively should be based on clinical assessment of adequacy of wound healing. Safety of resuming axitinib after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome

Reversible posterior leukoencephalopathy syndrome (RPLS), a neurologic disorder, reported in one axitinib-treated patient (<1%) in the primary efficacy study; 2 additional cases reported in other clinical trials. May manifest with headache, seizures, lethargy, confusion, blindness, and other visual and neurologic disturbances; mild to severe hypertension also may occur. Magnetic resonance imaging (MRI) is necessary to confirm diagnosis.

In patients who develop signs or symptoms of RPLS, discontinue axitinib. Safety of reinitiating axitinib in patients previously experiencing RPLS not known.

Proteinuria

Proteinuria reported.

Monitor for proteinuria prior to initiation of, and periodically during, therapy. For moderate to severe proteinuria, reduce dosage or temporarily interrupt therapy.

Hepatic Effects

ALT elevations, sometimes severe, reported in 22% of patients receiving axitinib monotherapy in the primary efficacy study. Monitor serum aminotransferase (ALT and AST) and bilirubin concentrations prior to initiation of, and periodically during, axitinib monotherapy. More frequent monitoring of liver tests should be considered when axitinib is used in combination with avelumab or pembrolizumab.

Axitinib in combination with avelumab or pembrolizumab can cause hepatotoxicity with higher than expected frequencies of grade 3 or 4 ALT or AST elevations.

Major Adverse Cardiovascular Events

Cardiovascular events, sometimes severe and fatal, reported when used in combination with avelumab.

Consider assessing LVEF at baseline and periodically. Monitor for signs and symptoms of cardiovascular events, and optimize management of cardiovascular risk factors (e.g., hypertension, diabetes, dyslipidemia). Discontinue axitinib and avelumab if grade 3 or 4 cardiovascular events occur.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity, embryotoxicity, and fetotoxicity demonstrated in animals.

Avoid pregnancy during therapy. If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.

Combination Therapy

When axitinib is used in combination with avelumab or pembrolizumab, consider the usual cautions, precautions, and contraindications associated with avelumab and pembrolizumab in addition to those associated with axitinib.

Infertility

Based on findings in animals, axitinib may impair fertility in females and males of reproductive potential.

Specific Populations

Pregnancy

May cause fetal harm.

Lactation

Not known whether axitinib is distributed into human milk. Do not breast-feed during therapy and for 2 weeks after the last dose.

Females and Males of Reproductive Potential

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

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age. Pharmacokinetics of axitinib in pediatric patients not studied.

Thickened growth plates in bone and abnormalities in growing incisor teeth observed in juvenile animals receiving oral axitinib for ≥1 month; other toxicities of potential concern not evaluated in juvenile animal studies.

Geriatric Use

No overall differences in safety and efficacy relative to younger patients, but increased sensitivity cannot be ruled out.

Hepatic Impairment

Systemic exposure not affected by mild hepatic impairment (Child-Pugh class A).

Increased systemic exposure in patients with moderate hepatic impairment (Child-Pugh class B); initial dosage reduction recommended.

Not studied in patients with severe hepatic impairment (Child-Pugh class C).

Renal Impairment

Mild to severe renal impairment unlikely to substantially affect pharmacokinetics (e.g., clearance) of axitinib; no initial dosage adjustment necessary.

Limited data in patients with end-stage renal disease; use with caution.

Common Adverse Effects

Combination therapy with avelumab for the first-line treatment of advanced renal cell carcinoma (≥20%): Diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia (hand-foot syndrome), dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain, headache.

Combination therapy with pembrolizumab for the first-line treatment of advanced renal cell carcinoma (≥20%): Diarrhea, fatigue/asthenia, hypertension, hypothyroidism, decreased appetite, hepatotoxicity, palmar-plantar erythrodysesthesia (hand-foot syndrome), nausea, stomatitis/mucosal inflammation, dysphonia, rash, cough, constipation.

Monotherapy for the second-line treatment of advanced renal cell carcinoma (incidence ≥20%): Diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, palmar-plantar erythrodysesthesia (hand-foot syndrome), weight loss, vomiting, asthenia, constipation.

Interactions for Axitinib

Metabolized principally by CYP3A4/5 and, to a lesser extent, by CYP1A2, CYP2C19, and uridine diphosphate-glucurosyltransferase (UGT) 1A1.

Has potential to inhibit CYP isoenzymes 1A2 and 2C8 in vitro.

In vitro studies indicate that axitinib does not inhibit CYP2A6, 2C9, 2C19, 2D6, 2E1, 3A4/5, or UGT1A1 at therapeutic plasma concentrations.

Inhibition of P-glycoprotein (P-gp) not expected at therapeutic plasma concentrations.

Axitinib does not induce CYP1A1, CYP1A2, or CYP3A4/5 in human hepatocytes in vitro.

Drugs and Foods Affecting Hepatic Microsomal Enzymes

Potent CYP3A4/5 inhibitors: Possible pharmacokinetic interaction (increased plasma concentrations of axitinib). Avoid concomitant use; select an alternative agent with no or minimal enzyme inhibition potential. If concomitant therapy cannot be avoided, reduce axitinib dosage by approximately 50%; may increase or decrease subsequent dosages based on individual safety and tolerability. If the potent CYP3A4/5 inhibitor is discontinued, resume axitinib (after 3–5 elimination half-lives of the CYP3A4/5 inhibitor) at the dosage used prior to initiation of the potent CYP3A4/5 inhibitor.

CYP3A4/5 inducers: Possible pharmacokinetic interaction (decreased plasma concentrations of axitinib). Avoid concomitant use of potent CYP3A4/5 inducers; select an alternative agent with no or minimal enzyme induction potential. Also avoid concomitant use of moderate CYP3A4/5 inducers if possible.

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP isoenzymes 1A2 or 2C8: Clinically important pharmacokinetic interactions unlikely.

Drugs Affecting Gastric Acidity

Pharmacokinetic interaction (possible decreased solubility of axitinib) with drugs that increase pH of upper GI tract. Clinically important pharmacokinetic interaction unlikely.

Specific Drugs and Foods

Drug

Interaction

Comments

Antacids

Possible decreased solubility of axitinib; clinically important pharmacokinetic interaction unlikely

Dosage adjustment not necessary

Antifungals, azoles (e.g., itraconazole, ketoconazole, voriconazole)

Possible increased axitinib concentrations

Ketoconazole (400 mg once daily) increased peak concentrations and AUC of axitinib (single 5-mg dose) by 1.5- and 2-fold, respectively

Avoid concomitant use

Select an alternative agent with no or minimal enzyme inhibition potential; if concomitant use cannot be avoided, reduce axitinib dosage by approximately 50% and adjust subsequent dosage based on individual safety and tolerability

If the potent CYP3A4/5 inhibitor is discontinued, resume axitinib (after 3–5 terminal half-lives of the CYP3A4/5 inhibitor) at the dosage used prior to initiation of the potent CYP3A4/5 inhibitor

Antimycobacterials, rifamycins (e.g., rifabutin, rifampin, rifapentine)

Possible decreased axitinib concentrations

Rifampin decreased peak concentrations and AUC of axitinib by 71 and 79%, respectively

Avoid concomitant use; select an alternative agent with no or minimal enzyme induction potential

Antiretrovirals, HIV protease inhibitors (e.g., atazanavir, indinavir, nelfinavir, ritonavir, saquinavir)

Possible increased axitinib concentrations

Avoid concomitant use

Select an alternative agent with no or minimal enzyme inhibition potential; if concomitant use cannot be avoided, reduce axitinib dosage by approximately 50% and adjust subsequent dosage based on individual safety and tolerability

If the potent CYP3A4/5 inhibitor is discontinued, resume axitinib (after 3–5 terminal half-lives of the CYP3A4/5 inhibitor) at the dosage used prior to initiation of the potent CYP3A4/5 inhibitor

Antiretrovirals, nonnucleoside reverse transcriptase inhibitors (NNRTIs)

Efavirenz, etravirine: Possible decreased axitinib concentrations

Avoid concomitant use of efavirenz and etravirine if possible

Bevacizumab

Pharmacokinetic interaction unlikely

Bosentan

Possible decreased axitinib concentrations

Avoid concomitant use if possible

Carbamazepine

Possible decreased axitinib concentrations

Avoid concomitant use; select an alternative agent with no or minimal enzyme induction potential

Carboplatin

Pharmacokinetic interaction unlikely

Cisplatin

Pharmacokinetic interaction unlikely

Dexamethasone

Possible decreased axitinib concentrations

Avoid concomitant use; select an alternative agent with no or minimal enzyme induction potential

Fluorouracil

Pharmacokinetic interaction unlikely

Gemcitabine

Pharmacokinetic interaction unlikely

Grapefruit or grapefruit juice

Possible increased axitinib concentrations

Avoid concomitant use

Histamine H2-receptor antagonists

Possible decreased solubility of axitinib; clinically important pharmacokinetic interaction unlikely

Irinotecan

Pharmacokinetic interaction unlikely

Macrolides (clarithromycin, telithromycin)

Possible increased axitinib concentrations

Avoid concomitant use

Select an alternative agent with no or minimal enzyme inhibition potential; if concomitant use cannot be avoided, reduce axitinib dosage by approximately 50% and adjust subsequent dosage based on individual safety and tolerability

If the potent CYP3A4/5 inhibitor is discontinued, resume axitinib (after 3–5 terminal half-lives of the CYP3A4/5 inhibitor) at the dosage used prior to initiation of the potent CYP3A4/5 inhibitor

Modafinil

Possible decreased axitinib concentrations

Avoid concomitant use if possible

Nafcillin

Possible decreased axitinib concentrations

Avoid concomitant use if possible

Nefazodone

Possible increased axitinib concentrations

Avoid concomitant use

Select an alternative agent with no or minimal enzyme inhibition potential; if concomitant use cannot be avoided, reduce axitinib dosage by approximately 50% and adjust subsequent dosage based on individual safety and tolerability

If nefazodone is discontinued, resume axitinib (after 3–5 terminal half-lives of nefazodone) at the dosage used prior to initiation of nefazodone

Oxaliplatin

Pharmacokinetic interaction unlikely

Paclitaxel

Pharmacokinetic interaction unlikely

Phenobarbital

Possible decreased axitinib concentrations

Avoid concomitant use; select an alternative agent with no or minimal enzyme induction potential

Phenytoin

Peak concentrations and AUC of axitinib decreased by about tenfold

Avoid concomitant use; select an alternative agent with no or minimal enzyme induction potential

Proton-pump inhibitors (e.g., rabeprazole)

Possible decreased solubility of axitinib; however, rabeprazole only minimally decreased peak concentrations and AUC of axitinib

Dosage adjustment not necessary

St. John’s wort (Hypericum perforatum)

Possible decreased axitinib concentrations

Avoid concomitant use; select an alternative agent with no or minimal enzyme induction potential

Warfarin

Possible increased warfarin concentrations and risk of hemorrhagic events; however, potential interaction not systematically evaluated

Axitinib Pharmacokinetics

Absorption

Bioavailability

Readily absorbed following oral administration; peak plasma concentrations are attained within 2.5–4.1 hours.

Steady-state concentrations expected within 2–3 days.

Mean absolute bioavailability after single-dose oral administration is 58%.

Use in combination with avelumab or pembrolizumab does not appear to result in clinically relevant changes in exposure to axitinib, avelumab, or pembrolizumab compared to use of each drug alone.

Food

Administration with a high-fat, high-calorie meal increased AUC by 19% compared with overnight fasting; administration with a moderate fat meal decreased AUC by 10%.

Special Populations

Mild hepatic impairment (Child-Pugh class A) does not substantially affect systemic exposure. Moderate hepatic impairment (Child-Pugh class B) increases systemic exposure. Not studied in severe hepatic impairment (Child-Pugh class C).

Distribution

Extent

Not known whether distributed into human milk.

Plasma Protein Binding

>99% (preferentially to albumin and moderately to α1-acid glycoprotein).

Elimination

Metabolism

Predominantly metabolized in liver by CYP3A4/5 and, to a lesser extent, by CYP1A2, CYP2C19, and UGT1A1.

Use in combination with avelumab does not appear to result in clinically relevant changes in clearance of avelumab compared to use of each agent alone.

Elimination Route

Primarily eliminated in feces (approximately 41%), mainly as unchanged drug, and in urine (approximately 23%), mainly as carboxylic acid and sulfoxide metabolites.

Half-life

2.5–6.1 hours.

Special Populations

Mild to severe renal impairment did not substantially alter clearance of axitinib in a population pharmacokinetic analysis. Data in end-stage renal disease very limited.

Stability

Storage

Oral

Tablets

20–25°C; excursions permitted between 15–30ºC.

Actions

  • Potently and selectively inhibits receptor tyrosine kinases, including vascular endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3. VEGFR receptors are involved in tumor angiogenesis, tumor growth, and metastatic spread.

  • Axitinib is 50–450 times more potent at blocking VEGFR receptors compared with first-generation VEGFR inhibitors (i.e., sorafenib, sunitinib, pazopanib).

  • Compared with first-generation VEGFR inhibitors, axitinib has relatively less potent or minimal inhibitory activity against other receptor kinases, including platelet-derived growth factor beta receptors (e.g., PDGFR-β), stem cell factor receptor (e.g., c-Kit), colony stimulating factor receptor type 1 (CSF-1R), fms-like tyrosine kinase 3 (Flt-3), fibroblast growth factor receptor (FGFR)-1, ret proto-oncogene (RET), epidermal growth factor receptor (EGFR), and met proto-oncogene encoding hepatocyte growth factor (c-MET).

  • Inhibits VEGF-mediated endothelial cell proliferation and survival in vitro and in mice.

  • Inhibits tumor growth and VEGFR-2 phosphorylation in mice.

Advice to Patients

  • Importance of reading the manufacturer’s patient information prior to beginning axitinib therapy and rereading it each time the prescription is refilled.

  • If a dose of axitinib is missed or vomited, take the next dose at the regularly scheduled time. Do not take more than one dose at a time.

  • Importance of swallowing axitinib tablets whole with a full glass of water. Avoid grapefruit or grapefruit juice while taking the drug.

  • Risk of hypertension. Importance of monitoring blood pressure regularly during treatment.

  • Risk of arterial and venous thromboembolic events. Importance of getting emergency help and contacting clinician if any symptoms suggestive of a thromboembolic event occur (e.g., chest pain or pressure, shortness of breath, unilateral numbness or weakness, difficulty talking, headache, vision changes, or arm, back, neck, or jaw pain).

  • Risk of bleeding. Importance of promptly informing clinician of any episodes of bleeding (e.g., unusual bleeding, bruising).

  • Increased risk of cardiac failure. Importance of advising patients of signs and symptoms of cardiac failure.

  • Risk of GI disorders. Importance of advising patients that GI disorders such as diarrhea, nausea, vomiting, and constipation may develop and to seek immediate medical attention if symptoms of GI perforation or fistula (e.g., persistent or severe abdominal pain, vomiting blood, red or black stools) occur.

  • Risk of thyroid dysfunction. Importance of informing clinician if symptoms of thyroid dysfunction occur (e.g., persistent or worsening fatigue, deepened voice, hair loss, weight gain or loss, myalgia, feeling hot or cold).

  • Risk of wound healing complications. Importance of informing clinician of any scheduled surgery or wounds that do not heal.

  • Risk of reversible posterior leukoencephalopathy syndrome (RPLS). Importance of immediately informing clinician if headache, seizures, weakness, lethargy, confusion, hypertension, blindness, or other visual and neurologic disturbances occur.

  • Risk of fetal harm and fetal loss. Importance of women informing their clinicians if they are or plan to become pregnant. Importance for men who are taking axitinib to inform their clinician if their female partner becomes pregnant. Necessity of advising women and men receiving axitinib to use effective methods of contraception during axitinib therapy and for 1 week after the last dose. Necessity of advising women to avoid pregnancy during therapy. Advise women of the potential risk to the fetus (e.g., birth defects) and/or the potential risk for loss of the pregnancy.

  • Risk of infertility. Importance of informing patients of the potential risk of infertility.

  • Importance of advising women to avoid breast-feeding while receiving axitinib and for 2 weeks after the last dose.

  • Risk of proteinuria and importance of monitoring for proteinuria before and during therapy.

  • Risk of hepatotoxicity; importance of liver function test monitoring during therapy.

  • Risk of major adverse cardiovascular effects. Importance of advising patients receiving axitinib in combination with avelumab to report signs or symptoms of cardiovascular events (e.g., chest discomfort, dyspnea, peripheral edema).

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements (e.g., St. John’s wort), as well as any concomitant illnesses (e.g., hypertension or other cardiovascular disease, cerebrovascular disease, thyroid disease, hepatic disease, bleeding disorders).

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Distribution of axitinib is restricted. Axitinib can only be obtained through designated specialty pharmacies. Contact manufacturer for specific availability information.

Axitinib

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

1 mg

Inlyta

Pfizer

5 mg

Inlyta

Pfizer

AHFS DI Essentials™. © Copyright 2022, Selected Revisions April 6, 2022. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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