axitinib

Action

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

Availability

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

Contraindications

None

Precautions

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).

Administration

• 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.

See 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

Interactions

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

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.

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

See 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.

See 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.