TA can cause fetal harm when administered to a pregnant woman based on its mechanism of action. There are no adequate and well-controlled studies in pregnant women using INLYTA. In developmental toxicity studies in mice, axitinib was teratogenic, embryotoxic and fetotoxic at maternal exposures that were lower than human exposures at the recommended clinical dose.
Women of childbearing potential should be advised to avoid becoming pregnant while receiving INLYTA. If this drug is used during pregnancy, or if a patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1)].
6 ADVERSE REACTIONS
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety of INLYTA has been eva luated in 715 patients in monotherapy studies, which included 537 patients with advanced RCC. The data described [see Adverse Reactions (6.1)] reflect exposure to INLYTA in 359 patients with advanced RCC who participated in a randomized clinical study versus sorafenib [see Clinical Studies (14)].
The following risks, including appropriate action to be taken, are discussed in greater detail in other sections of the label [see Warnings and Precautions (5.1–5.10 and 5.12)]: hypertension, arterial thromboembolic events, venous thromboembolic events, hemorrhage, gastrointestinal perforation and fistula formation, thyroid dysfunction, wound healing complications, RPLS, proteinuria, elevation of liver enzymes, and fetal development.
6.1 Clinical Trials Experience
The median duration of treatment was 6.4 months (range 0.03 to 22.0) for patients who received INLYTA and 5.0 months (range 0.03 to 20.1) for patients who received sorafenib. Dose modifications or temporary delay of treatment due to an adverse reaction occurred in 199/359 patients (55%) receiving INLYTA and 220/355 patients (62%) receiving sorafenib. Permanent discontinuation due to an adverse reaction occurred in 34/359 patients (9%) receiving INLYTA and 46/355 patients (13%) receiving sorafenib.
The most common (≥20%) adverse reactions observed following treatment with INLYTA were diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, palmar-plantar erythrodysesthesia (hand-foot) syndrome, weight decreased, vomiting, asthenia, and constipation. Table 1 presents adverse reactions reported in ≥10% patients who received INLYTA or sorafenib.
Table 1. Adverse Reactions Occurring in ≥10% of Patients Who Received INLYTA or Sorafenib
Adverse Reaction*
INLYTA
Sorafenib
(N=359)
(N=355)
All Grades†
Grade 3/4
All Grades†
Grade 3/4
%
%
%
%
* Percentages are treatment-emergent, all-causality events † National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0
Diarrhea
55
11
53
7
Hypertension
40
16
29
11
Fatigue
39
11
32
5
Decreased appetite
34
5
29
4
Nausea
32
3
22
1
Dysphonia
31
0
14
0
Palmar-plantar erythrodysesthesia syndrome
27
5
51
16
Weight decreased
25
2
21
1
Vomiting
24
3
17
1
Asthenia
21
5
14
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