Class: Tyrosine kinase inhibitor
- Tablets, oral 1 mg
- Tablets, oral 5 mg
Inhibits tumor cell proliferation and survival in vitro.
Bioavailability is 58%. T max is 2.5 to 4 h. Administration with high-fat meals increased AUC by 19%.
More than 99% bound to plasma proteins, primarily albumin. The Vd is 160 L.
Metabolism occurs primarily in the liver by CYP3A4/5 and to a lesser extent by CYP1A2, CYP2C19, and UGT1A1.
Half-life is 2.5 to 6 h. After oral administration, 41% was recovered in the feces (majority as unchanged axitinib) and 23% in the urine (majority as metabolites). Cl was 38 L/h.
Special PopulationsRenal Function Impairment
Mild to severe renal impairment had no meaningful effect on the pharmacokinetics of axitinib.Hepatic Function Impairment
Systemic exposure was similar in subjects with mild hepatic impairment (Child-Pugh class A) and higher in subjects with moderate impairment (Child-Pugh class B). Not studied in severe impairment (Child-Pugh class C).Elderly
Age has no clinically relevant effects on Cl.Children
Gender has no clinically relevant effects on Cl.Race
Race has no clinically relevant effects on Cl.
Indications and Usage
Treatment of advanced renal cell carcinoma after failure of 1 prior systemic therapy.
None well documented.
Dosage and AdministrationAdults
PO 5 mg twice daily initially. Patients who tolerate this dosage for at least 2 consecutive weeks with no adverse reactions greater than grade 2, are normotensive, and are not receiving antihypertensive medication may have their dosage increased to 7 mg twice daily, and further to 10 mg twice daily using the same criterion.Dosage adjustment
If a dosage reduction from 5 mg twice daily is required because of adverse reactions, the recommended dosage is 3 mg twice daily. If an additional dose reduction is required, the recommended dosage is 2 mg twice daily.Concomitant therapy
Strong CYP3A4/5 inhibitors
The concomitant use of strong CYP3A4/5 inhibitors should be avoided (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole). If a strong CYP3A4/5 inhibitor must be coadministered, a dose decrease of axitinib by approximately half is recommended. The subsequent doses can be increased or decreased based on individual safety and tolerability. If coadministration of the strong inhibitor is discontinued, the axitinib dose should be returned (after 3 to 5 half-lives of the inhibitor) to that used prior to initiation of the strong CYP3A4/5 inhibitor.CYP3A4/5 inducers
Avoid the concomitant use of strong CYP3A4/5 inducers (eg, rifampin, dexamethasone, phenytoin, carbamazepine, rifabutin, rifapentine, phenobarbital, St. John's wort). Moderate CYP3A4/5 inducers (eg, bosentan, efavirenz, etravirine, modafinil, nafcillin) should be avoided if possible.Hepatic Function Impairment
Decrease the starting dose by approximately half in patients with baseline moderate hepatic impairment (Child-Pugh class B). Subsequent doses may be increased or decreased based on individual safety and tolerability.
- Administer each dose approximately 12 h apart with or without food. Swallow whole with a glass of water.
- If the patient vomits or if a dose is missed, an additional dose should not be taken. The next prescribed dose should be taken at the usual time.
Store between 59° and 86°F.
Drug InteractionsGrapefruit or grapefruit juice
May increase axitinib plasma concentrations and should be avoided.Moderate CYP3A4/5 inducers (eg, bosentan, efavirenz, etravirine, modafinil, nafcillin)
Axitinib plasma concentration may be reduced. Avoid coadministration if possible.Strong CYP3A4/5 inducers (eg, carbamazepine, dexamethasone, phenobarbital, phenytoin, rifamycins [eg, rifampin], St. John's wort)
Coadministration will reduce axitinib plasma concentration. Avoid coadministration.Strong CYP3A4/5 inhibitors (eg, clarithromycin, HIV protease inhibitors [eg, ritonavir], itraconazole, ketoconazole, nefazodone, telithromycin, voriconazole)
Avoid coadministration because of the risk of increased axitinib plasma concentration. If coadministration cannot be avoided, reduce the axitinib dosage.
Hypertension (40%); deep vein thrombosis, transient ischemic attack (1%).
Fatigue (39%); asthenia (21%); headache (14%); dizziness (9%).
Rash (13%); dry skin (10%); pruritus (7%); alopecia (4%); erythema (2%).
Dysphonia (31%); dysgeusia (11%); tinnitus (3%); retinal vein occlusion/thrombosis (1%).
Diarrhea (55%); nausea (32%); vomiting (24%); constipation (20%); stomatitis (15%); abdominal pain (14%); dyspepsia (10%); upper abdominal pain (8%); hemorrhoids (4%); rectal hemorrhage (2%).
Proteinuria (11%); hematuria (3%).
Anemia (4%); polycythemia (1%).
Creatinine increased (55%); bicarbonate decreased (44%); Hgb decreased (35%); absolute lymphocytes decreased (33%); alkaline phosphatase increased (30%); lipase increased (27%); amylase increased (25%); ALT increased (22%); AST increased (20%); platelets decreased (15%); WBC decreased (11%); Hgb increased (9%).
Hypocalcemia (39%); decreased appetite (34%); hyperglycemia (28%); weight decreased (25%); hypothyroidism (19%); hypernatremia (17%); hyperkalemia, hypoalbuminemia (15%); hyponatremia, hypophosphatemia (13%); hypoglycemia (11%); dehydration (6%).
Arthralgia (15%); pain in extremity (13%); myalgia (7%).
Cough, dyspnea (15%); epistaxis (6%); hemoptysis, pulmonary embolism (2%).
Palmar-plantar erythrodysesthesia syndrome (27%); mucosal inflammation (15%).
Monitor for hypertension. Monitor for symptoms of GI perforation or fistula periodically during treatment. Monitor ALT, AST, bilirubin, and thyroid function, and for proteinuria before initiation of, and periodically throughout, treatment.
Category D . Advise women of childbearing potential to avoid becoming pregnant.
Safety and efficacy not studied.
Use with caution in patients with ESRD (CrCl less than 15 mL/min).
Adjust dose in patients with moderate hepatic impairment. Axitinib has not been studied in patients with severe hepatic impairment.
GI perforation or fistula may occur.
Hemorrhage, including fatal cases, has been reported. If any bleeding requires medical intervention, temporarily interrupt axitinib treatment.
ALT elevations have been reported.
Hypertension has been reported; BP increases were observed as early as 4 days after initiation. Hypertensive crisis was seen in less than 1% of patients. BP should be well controlled before initiating axitinib.
Has been reported; reduce dose or temporarily interrupt therapy.
Reversible posterior leukoencephalopathy syndrome
Has been reported; discontinue therapy in patients developing reversible posterior leukoencephalopathy syndrome.
Arterial and venous thromboembolic events, including deaths, have been reported. Use with caution in patients at risk of thromboembolic events.
Hyper- and hypothyroidism have been reported.
Stop treatment at least 24 h prior to scheduled surgery. Base the decision to resume treatment on clinical judgement and adequate wound healing.
Dizziness, fatal hemoptysis, hypertension, seizures associated with hypertension.
- Advise patients that hypertension may develop during treatment and that BP should be monitored regularly.
- Advise patients that arterial and venous thromboembolic events have been observed during treatment and to inform their health care provider if they experience symptoms suggestive of thromboembolic events.
- Advise patients that axitinib may increase the risk of bleeding and to promptly inform their health care provider of any bleeding episodes.
- Advise patients that GI disorders, such as diarrhea, nausea, vomiting, and constipation, may develop during treatment and to seek immediate medical attention if they experience severe or persistent abdominal pain.
- Advise patients that abnormal thyroid function may develop during treatment and to inform their health care provider if symptoms of abnormal thyroid function occur.
- Advise patients to inform their health care provider if they have an unhealed wound or if they have a surgery scheduled.
- Advise patients to inform their health care provider if they have symptoms suggestive of reversible posterior leukoencephalopathy syndrome (eg, headache, seizure, lethargy, confusion, blindness, other visual disturbances).
- Advise patients that axitinib may cause birth defects or fetal loss and that they should not become pregnant during treatment. Counsel patients to use effective birth control during treatment. Advise female patients not to breast-feed during therapy.
- Advise patients to inform their health care provider of all concomitant medications, vitamins, or dietary and herbal supplements.
Copyright © 2009 Wolters Kluwer Health.
More about axitinib
- Other brands: Inlyta