Pharmacologic class: Kinase inhibitor

Therapeutic class: Antineoplastic

Pregnancy risk category D


Inhibits receptor tyrosine kinases, including vascular endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3 at therapeutic plasma concentrations that are implicated in pathologic angiogenesis, tumor growth, and cancer progression


Tablets: 1 mg, 5 mg

Indications and dosages

Advanced renal cell carcinoma after failure of one prior systemic therapy

Adults: Initially, 5 mg P.O. b.i.d., with dosage adjustments based on individual safety and tolerability

Dosage adjustment

• Moderate hepatic impairment

• Moderate to severe proteinuria

• Concurrent use of strong CYP3A4/5 inhibitors




Use cautiously in:

• moderate hepatic impairment, proteinuria, end-stage renal disease (creatinine clearance less than 15 ml/minute)

• severe hepatic impairment (safety and efficacy not established)

• persistent hypertension, hypothyroidism, reversible posterior leukoencephalopathy syndrome

• patient at increased risk for arterial and venous thrombotic events or GI perforation or fistula

• patient with untreated brain metastasis or recent active GI bleeding (avoid use)

• patient undergoing surgery

• concurrent use of moderate or strong CYP3A4/5 inducers or strong CYP3A4/5 inhibitors, grapefruit, grapefruit juice (avoid use)

• pregnant or breastfeeding patients

• children younger than age 18 (safety and efficacy not established).


• Administer tablets whole with a glass of water approximately 12 hours apart with or without food.

• Don't give with grapefruit juice.

• Ensure that blood pressure is well controlled and assess thyroid function before starting drug.

• Watch for proteinuria before starting drug; reduce dosage or temporarily interrupt treatment if moderate to severe proteinuria occurs during treatment.

• Evaluate patient for elevated ALT, AST, and bilirubin levels; decrease starting dosage as appropriate in patients with moderate hepatic impairment.

Permanently discontinue drug if signs or symptoms of posterior leukoencephalopathy syndrome occur (such as headache, seizures, lethargy, confusion, blindness, or other visual and neurologic disturbances).

• Stop drug at least 24 hours before scheduled surgery.

Adverse reactions

CNS: headache, fatigue, asthenia, posterior leukoencephalopathy syndrome

CV: hypertension

GI: nausea, vomiting, diarrhea, constipation, stomatitis, abdominal pain, dyspepsia, GI perforation or fistula

GU: proteinuria

Hematologic: hemorrhagic events

Hepatic: increased ALT, AST, and bilirubin levels

Metabolic: hypothyroidism, hypocalcemia, hyperglycemia, hypoglycemia, hyperkalemia, hyponatremia, hypophosphatemia

Musculoskeletal: arthralgia, extremity pain

Respiratory: cough, dyspnea

Skin: rash, dry skin, pruritus, erythema, alopecia

Other: decreased appetite, dysphonia, dysgeusia, weight loss, mucosal inflammation, palmar-plantar erythrodysesthesia syndrome


Drug-drug. Antacids (such as rabeprazole): decreased axitinib area under the curve and Cmax

Moderate CYP3A4/5 inducers (such as bosentan, efavirenz, etravirine, modafinil, nafcillin): possibly decreased axitinib plasma exposure

Strong CYP3A4/5 inducers (such as carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, rifapentin): decreased axitinib plasma exposure

Strong CYP3A4/5 inhibitors (such as ketoconazole): increased axitinib plasma exposure

Drug-diagnostic tests. Albumin, bicarbonate, calcium, hemoglobin, lymphocytes, phosphorus, platelets, WBCs: decreased levels

Alkaline phosphatase, ALT, amylase, AST, creatinine, lipase, potassium, sodium: increased levels Serum glucose: increased or decreased level

Drug-food. Grapefruit, grapefruit juice: increased axitinib plasma exposure

Drug-herbs. St. John's wort: decreased axitinib plasma exposure

Patient monitoring

• Monitor CBC with differential and renal function (especially for proteinuria) and hepatic function tests closely.

• Continue to monitor thyroid function periodically throughout treatment.

Closely monitor patient at risk for arterial and venous thrombotic events, hemorrhagic events, and GI perforation and fistula.

Continue to monitor patient for posterior leukoencephalopathy syndrome.

Patient teaching

• Tell patient to take tablets whole with a glass of water approximately 12 hours apart with or without food.

• Tell patient not to take drug with grapefruit juice or grapefruit products.

• Advise patient that hypertension may develop during treatment and that blood pressure should be monitored regularly.

Instruct patient to immediately report signs or symptoms of arterial and venous thromboembolic events (such as chest pain or pressure, shortness of breath, numbness or weakness on one side of body, difficulty speaking, or vision changes), bleeding, or persistent or severe abdominal pain.

• Advise patient to report signs and symptoms of decreased thyroid function (such as fatigue, weight gain, depression, sensitivity to cold, brittle hair and nails, and thinning hair).

• Instruct patient to report signs and symptoms of palmar-plantar erythrodysesthesia syndrome (such as redness, swelling, tingling or burning, tenderness, or skin tightness on palms of hands or soles of feet).

• Instruct patient to tell prescriber about all drugs he's taking, because some drugs have potential for serious drug interactions.

• Advise female patient of childbearing age to avoid pregnancy and breastfeeding while taking this drug.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.

McGraw-Hill Nurse's Drug Handbook, 7th Ed. Copyright © 2013 by The McGraw-Hill Companies, Inc. All rights reserved


(ax-i-ti-nib) ,


(trade name)


Therapeutic: antineoplastics
Pharmacologic: kinase inhibitors
Pregnancy Category: D


Treatment of advanced renal cell carcinoma following failure of one other systemic therapy.


Inhibits tyrosine kinases on various receptors including vascular endothelial growth factor receptors which may be involved in tumor angiogenesis/growth and cancer progression.

Therapeutic effects

Inhibited tumor growth with decreased disease progression.


Absorption: Well absorbed (58%) following oral administration.
Distribution: Unknown.
Protein Binding: >99%.
Metabolism and Excretion: Mostly metabolized by the CYP3A4/5 enzyme system, some metabolism by CYP2C19 and UGT1A1 systems. 41 % eliminated in feces (12% as unchanged drug); 23% eliminated in urine as metabolites.
Half-life: 2.5–6.1 hr.

Time/action profile (blood levels)

POunknown2.5–4.1 hr 12 hr
† Decreased progression of disease may last up to 18 mo.


Contraindicated in: Strong CYP3A4/5 inhibitors (avoid if possible); Strong CYP3A4/5 inducers (avoid if possible); Obstetric: May cause fetal harm; Lactation: Breast-feeding should be avoided.
Use Cautiously in: History of hypertension (must be well-controlled prior to/during therapy); Moderate hepatic impairment (dose reduction recommended); Surgery (discontinue 24 hr prior if possible); End-stage renal disease (CCr <15 mL/min); Woman with child-bearing potential; Pediatric: Safety and effectiveness not established.

Adverse Reactions/Side Effects

Central nervous system

  • reversible posterior leukoencephalopathy syndrome (RPLS) (life-threatening)
  • dysphoria (most frequent)
  • fatigue (most frequent)
  • headache (most frequent)

Ear, Eye, Nose, Throat

  • dysphonia (most frequent)


  • cough (most frequent)


  • hypertension
  • aterial/venous thromboembolic events (life-threatening)


  • GI perforation/fistula (life-threatening)
  • abdominal pain (most frequent)
  • altered taste (most frequent)
  • ↓ appetite/weight (most frequent)
  • constipation (most frequent)
  • diarrhea (most frequent)
  • nausea (most frequent)
  • ↑ liver enzymes (most frequent)
  • stomatitis (most frequent)
  • burning mouth


  • ↑ creatinine (most frequent)
  • proteinuria (most frequent)


  • dry skin (most frequent)
  • palmar-plantar erythrodysesthesia (hand-foot syndrome)
  • rash (most frequent)
  • alopecia
  • erythema
  • pruritus


  • hypothyroidism (most frequent)

Fluid and Electrolyte

  • ↓ bicarbonate (most frequent)
  • hyperglycemia (most frequent)
  • hyperkalemia (most frequent)
  • hypernatremia (most frequent)
  • hypoalbuminemia
  • hypocalcemia (most frequent)
  • hypoglycemia (most frequent)
  • hyponatremia (most frequent)
  • hypophosphatemia (most frequent)
  • hypercalcemia


  • bleeding (life-threatening)
  • anemia (most frequent)
  • neutropenia (most frequent)
  • thrombocytopenia (most frequent)


  • arthralgia (most frequent)
  • extremity pain (most frequent)


Drug-Drug interaction

Strong CYP3A4/5 inhibitors including atazanavir, clarithromycin, indinaviritraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, telithromycin, voriconazole ↑ levels and the risk of toxicity (avoid if possible); selection of alternative agents is strongly recommended. If none is acceptable, axitinib dose should be ↓ by 50%, with return to previous dose when inhibitor is discontinued.Strong inducers CYP3A4/5 inducers including carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, and rifapentin may ↓ levels and effectiveness and should be avoided if possible. Similar effects may occur with mild inducers including bosentan, efavirenz, etravirine, modafinil and nafcillin.St. John's wort may ↓ levels and should be avoided.Grapefruit/grapefruit juice may ↑ levels and should be avoided.


Oral (Adults) 5 mg twice daily, approximately 12 hr apart initially; after 2 wk may be ↑ to 7 mg twice daily and after a further 2 wk to 10 mg twice daily. Subsequent adjustments depend on tolerability and safety. Concurrent strong CYP3A4/5 inhibitors—↓ dose by approximately 50%, subsequent adjustments depend on tolerability and safety.

Hepatic Impairment

Oral (Adults) Moderate hepatic impairment (Child-Pugh Class B)— ↓ dose by 50%, further adjustments depend on tolerability and safety.


Tablets : 1 mg, 5 mg

Nursing implications

Nursing assessment

  • Monitor BP periodically during therapy. May cause hypertension. If unresponsive to antihypertensives, may require decreased dose.
  • Monitor for bleeding. If any bleeding requires medical intervention, consider permanent discontinuation of axitinib.
  • Lab Test Considerations: Monitor serum thyroid prior to and periodically during therapy. May cause hypothyroidism or hyperthyroidism. Treat with standard therapy.
    • Monitor for proteinuria prior to and periodically during therapy. If moderate to severe proteinuria occurs, reduce dose or temporarily discontinue axitinib therapy.
    • Monitor liver function tests prior to and periodically during therapy. May cause ↑ ALT, AST and bilirubin.
    • May cause ↑ serum creatinine, ALP, blood sugar, lipase, amylase, sodium, potassium and ↓ hemoglobin, absolute lymphocytes, platelets, bicarbonate, serum calcium, albumin, blood sugar, sodium, and phosphate.

Potential Nursing Diagnoses

Deficient knowledge, related to medication regimen (Patient/Family Teaching)


  • Oral: Administer twice daily with doses 12 hrs apart. May be administered with or without food. Swallow tablets whole followed by a full glass of water.

Patient/Family Teaching

  • Instruct patient to take axitinib as directed. If a dose is vomited or missed, omit dose and take next dose at regular time; do not double doses.
  • Advise patient to avoid drinking grapefruit juice or eating grapefruit during axitinib therapy.
  • Advise patient to notify health care professional of therapy prior to treatment, dental procedure, or surgery. Axitinib therapy should be interrupted in patients undergoing major surgery.
  • May cause bleeding or blood clots. Advise patient to notify health care professional immediately if unexpected bleeding or bleeding that lasts a long time; unusual bleeding of gums; heavier than normal menstrual bleeding; severe or uncontrollable bleeding; pink or brown urine; red or black stools; vomiting blood or dark “coffee ground” looking; unexpected pain, swelling, or joint pain; headaches; feeling dizzy; or weakness occur or if chest pain or pressure; pain in arms, back, neck or jaw; shortness of breath; numbness or weakness on one side of body; difficulty talking; headache; or vision changes occur.
  • May cause stomach tear or intestinal wall perforation. Caution patient to notify health care professional if severe abdominal pain, vomiting blood, or red or black stools occur.
  • Advise patient to notify health care professional promptly if signs and symptoms of reversible posterior leukoencephalopathy syndrome (RPLS) (headache, seizures, weakness, confusion, high BP, blindness or change in vision, problems thinking) occur.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's Wort.
  • May cause teratogenic effects. Advise both male and female patients to use effective contraception during therapy. Advise female patients to avoid breastfeeding during therapy.

Evaluation/Desired Outcomes

  • Decreased growth and spread of advanced renal cell carcinoma.
Drug Guide, © 2015 Farlex and Partners
References in periodicals archive ?
It is based on findings from the pivotal Phase 3 Keynote-426 trial, which demonstrated that Keytruda in combination with axitinib reduced the risk of death by 47% compared with sunitinib in patients with advanced RCC.
X4's most advanced product candidate, mavorixafor (X4P-001), is in a global Phase 3 pivotal trial in patients with WHIM syndrome, a rare, inherited, primary immunodeficiency disease, and is currently also under investigation in combination with axitinib in the Phase 2a portion of an open-label Phase 1/2 clinical trial in clear cell renal cell carcinoma (ccRCC).
* Merck announced that the European Medicines Agency (EMA) adopted a positive opinion for KEYTRUDA in combination with axitinib as a first-line treatment for advanced renal cell carcinoma (RCC) based on the findings from the pivotal KEYNOTE-426 trial.
"The positive opinion adopted by the EMA, which is based on data showing KEYTRUDA in combination with axitinib significantly improved overall survival regardless of PD-L1 expression, is an important step toward a new first-line treatment option for these patients," said Scot Ebbinghaus, VP, clinical research, Merck Research Labs.
in combination with axitinib for renal cell carcinoma and has been granted Priority Review by the FDA.
The research includes new insights on the drug manufacturer's marketed therapies, including Ibrance (palbociclib), Xtandi (enzalutamide), Talzenna (talazoparib), Bosulif (bosutinib), Inlyta (axitinib) and Bavencio (avelumab), which represent Pfizer Oncology's long-standing legacy of developing innovative therapies for patients in need, as well as its ongoing commitment to addressing the needs of cancer patients across gender, ethnicity and tumor type.
The United States Food and Drug Administration (FDA) has granted approval to United States-based Merck for its Keytruda in combination with Inlyta (axitinib) as first-line treatment for patients with advanced renal cell carcinoma, it was reported yesterday.
The study found that patients who received the immunotherapy drug avelumab plus axitinib, a targeted agent, had a significant advantage in progression-free survival compared with those who received sunitinib (Sutent), a targeted drug that has been a standard treatment for advanced clear cell renal cell carcinoma - the most common form of kidney cancer.
EMD Serono stated on Monday that its supplemental Biologics License Application (sBLA) for BAVENCIO (avelumab) in combination with INLYTA (axitinib) has passed US Food and Drug Administration (FDA) priority review in patients with advanced renal cell carcinoma (RCC), the most common form of kidney cancer.
[8] Meeting Library | ATLAS study: A randomized double-blind phase 3 study of adjuvant axitinib versus placebo in subjects at high risk of recurrent renal cell carcinoma (RCC).
The findings of the study involving the combination of anti-angiogenesis agent axitinib and the immunotherapy agent pembrolizumab.