%
%
%
ALP: alkaline phosphatase; ALT: alanine aminotransferase; AST: aspartate aminotransferase
* National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0
Hematology
Hemoglobin decreased
320
35
<1
316
52
4
Lymphocytes (absolute) decreased
317
33
3
309
36
4
Platelets decreased
312
15
<1
310
14
0
White blood cells decreased
320
11
0
315
16
<1
Chemistry
Creatinine increased
336
55
0
318
41
<1
Bicarbonate decreased
314
44
<1
291
43
0
Hypocalcemia
336
39
1
319
59
2
ALP increased
336
30
1
319
34
1
Hyperglycemia
336
28
2
319
23
2
Lipase increased
338
27
5
319
46
15
Amylase increased
338
25
2
319
33
2
ALT increased
331
22
<1
313
22
2
AST increased
331
20
<1
311
25
1
Hypernatremia
338
17
1
319
13
1
Hypoalbuminemia
337
15
<1
319
18
1
Hyperkalemia
333
15
3
314
10
3
Hypoglycemia
336
11
<1
319
8
<1
Hyponatremia
338
13
4
319
11
2
Hypophosphatemia
336
13
2
318
49
16
Selected laboratory abnormalities (all grades) that were reported in <10% of patients treated with INLYTA included hemoglobin increased (above the upper limit of normal) (9% for INLYTA versus 1% for sorafenib).
7 DRUG INTERACTIONS
In vitro data indicate that axitinib is metabolized primarily by CYP3A4/5 and, to a lesser extent, CYP1A2, CYP2C19, and uridine diphosphate-glucuronosyltransferase (UGT) 1A1.
7.1 CYP3A4/5 Inhibitors
Co-administration of ketoconazole, a strong inhibitor of CYP3A4/5, increased the plasma exposure of axitinib in healthy volunteers. Co-administration of INLYTA with strong CYP3A4/5 inhibitors should be avoided. Grapefruit or grapefruit juice may also increase axitinib plasma concentrations and should be avoided. Selection of concomitant medication with no or minimal CYP3A4/5 inhibition potential is recommended. If a strong CYP3A4/5 inhibitor must be co-administered, the INLYTA dose should be reduced [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].
7.2 CYP3A4/5 Inducers
Co-administration of rifampin, a strong inducer of CYP3A4/5, reduced the plasma exposure of axitinib in healthy volunteers. Co-administration of INLYTA with strong CYP3A4/5 inducers (e.g., rifampin, dexamethasone, phenytoin, carbamazepine, rifabutin, rifapentin, phenobarbital, and St. John's wort) should be avoided. Selection of concomitant medication with no or minimal CYP3A4/5 induction potential is recommended [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)]. Moderate CYP3A4/5 inducers (e.g., bosentan, efavirenz, etravirine, modafinil, and nafcillin) may also reduce the plasma exposure of axitinib and should be avoided if possible.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category D [see Warnings and Precaution
