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
• 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.
CNS: headache, fatigue, asthenia, posterior leukoencephalopathy syndrome
GI: nausea, vomiting, diarrhea, constipation, stomatitis, abdominal pain, dyspepsia, GI perforation or fistula
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
• 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.
• 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.
Pharmacologic: kinase inhibitors
Time/action profile (blood levels)
|PO||unknown||2.5–4.1 hr||12 hr|
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)
- 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)
- hypothyroidism (most frequent)
Fluid and Electrolyte
- ↓ bicarbonate (most frequent)
- hyperglycemia (most frequent)
- hyperkalemia (most frequent)
- hypernatremia (most frequent)
- hypocalcemia (most frequent)
- hypoglycemia (most frequent)
- hyponatremia (most frequent)
- hypophosphatemia (most frequent)
- bleeding (life-threatening)
- anemia (most frequent)
- neutropenia (most frequent)
- thrombocytopenia (most frequent)
- arthralgia (most frequent)
- extremity pain (most frequent)
Drug-Drug interactionStrong 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.
Hepatic ImpairmentOral (Adults) Moderate hepatic impairment (Child-Pugh Class B)— ↓ dose by 50%, further adjustments depend on tolerability and safety.
- 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 DiagnosesDeficient 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.
- 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.
- Decreased growth and spread of advanced renal cell carcinoma.