5.5  Laboratory Monitoring/Hypoalbuminemia
Monitor serum albumin levels prior to the initiation of each treatment course. Withhold administration of Ontak if serum albumin levels are less than 3.0 g/dL [see Dosage and Administration ( 2.1 ) and Warnings and Precautions ( 5.2 )].

6  ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of the label:

6.1  Clinical Studies Experience
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 practice.

Safety data are available for 3 clinical studies in which 234 patients received Ontak at 9 mcg/kg (n=80) or 18 mcg/kg (n=154) at the recommended schedule. Of these studies, 1 was placebo-controlled and dose-ranging (Study 1, 100 Ontak-treated patients), one was a dose-comparison of 9 and 18 mcg/kg (Study 2, n=71), and the third was a single-arm study using 18 mcg/kg (n=63); all studies were limited to adult patients with CTCL. The median age of patients across the clinical studies was 60 years (range 23-91 years) and 36% (n=85) were 65 years of age or older; 55% were men and 85% were Caucasian.

Across all 3 studies, the most common adverse reactions in Ontak-treated patients (≥20%) were pyrexia, nausea, fatigue, rigors, vomiting, diarrhea, headache, peripheral edema, cough, dyspnea and pruritus. The most common serious adverse reactions were capillary leak syndrome (11.1%), infusion reactions (8.1%), and visual changes including loss of visual acuity (4%). Ontak was discontinued in 28.2% (66/234) of patients due to adverse reactions.

The data described in Table 1 reflect exposure to Ontak in 100 patients administered as a single agent at the recommended dosing schedule in the randomized placebo-controlled trial (Study 1). The median number of Ontak cycles was 7 (range 1-10) for the 9 mcg/kg cohort and 6 (range 1-11) for the 18 mcg/kg cohort. The median age of patients was 59 years (range 23-84 years) and 34% (n=34) were 65 years of age or older; 55% were men and 86% were Caucasian.

Hepatobiliary Disorders: Increase in serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) from baseline occurred in 84% of subjects treated with Ontak (197/234). In the majority of subjects, these enzyme elevations occurred during either the first or the second cycle; enzyme elevation resolved without medical intervention and did not require discontinuation of Ontak.

Table 1: Incidence of Adverse Reactions Occurring in ≥10% of Ontak-treated patients (18 mcg/kg group) and at a higher rate than Placebo in Study 1 MedDRA version 6.1
Preferred Term  Placebo
N=44
n (%)  Ontak
9 mcg/kg
N=45
n (%)  Ontak
18 mcg/kg
N=55
n (%) 
Pyrexia 7 (15.9) 22 (48.9) 35 (63.6)
Nausea 10 (22.7) 21 (46.7) 33 (60.0)
Rigors 9 (20.5) 19 (42.2) 26 (47.3)
Fatigue 14 (31.8) 21 (46.7) 24 (43.6)
Vomiting 3 (6.8) 6 (13.3) 19 (34.5)
Headache 8 (18.2) 13 (28.9) 14 (25.5)
Edema peripheral 10 (22.7) 9 (20.0) 14 (25.5)
Diarrhea 4 (9.1) 10 (22.2) 12 (21.8)
Anorexia 2 (4.5) 4 (8.9) 11 (20.0)
Rash 2 (4.5) 11 (24.4) 11 (20.0)
Myalgia 2 (4.5) 8 (17.8) 11 (20.0)
Cough 3 (6.8) 9 (20.0) 10 (18.2)
Pruritus 4 (9.1) 7 (15.6) 10 (18.2)
Back pain 1 (2.3) 7