6 ADVERSE REACTIONS

The following clinically significant adverse reactions are described elsewhere in the labeling:

Myelosuppression [see Warnings and Precautions (5.1)]
Mucositis [see Warnings and Precautions (5.2)]
Dermatologic Reactions [see Warnings and Precautions (5.3)]
Tumor Lysis Syndrome [see Warnings and Precautions (5.4)]
Hepatic Toxicity [see Warnings and Precautions (5.5)]

6.1 Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Peripheral T-cell Lymphoma

The safety of FOLOTYN was evaluated in Study PDX-008 [see Clinical Studies (14)]. Patients received FOLOTYN 30 mg/m2 once weekly for 6 weeks in 7-week cycles. The median duration of treatment was 70 days (range: 1 day to 1.5 years). The majority of patients (69%, n = 77) remained at the target dose for the duration of treatment. Overall, 85% of scheduled doses were administered.

Forty-four percent of patients (n = 49) experienced a serious adverse event while on study or within 30 days after their last dose of FOLOTYN. The most common serious adverse events (> 3%), regardless of causality, were pyrexia, mucositis, sepsis, febrile neutropenia, dehydration, dyspnea, and thrombocytopenia. One death from cardiopulmonary arrest in a patient with mucositis and febrile neutropenia was reported in this trial. Across clinical trials, deaths from mucositis, febrile neutropenia, sepsis, and pancytopenia occurred in 1.2% of patients who received doses ranging from 30 mg/m2 to 325 mg/m2.

Twenty-three percent of patients (n = 25) discontinued treatment with FOLOTYN due to adverse reactions. The most frequent adverse reactions reported as the reason for discontinuation of treatment were mucositis (6%) and thrombocytopenia (5%).

The most common adverse reactions (> 35%) were mucositis, thrombocytopenia, nausea, and fatigue.

Table 4 summarizes the adverse reactions in Study PDX-008.

Table 4 Adverse Reactions in (≥ 10%) in Patients Who Received FOLOTYN in Study PDX-008
	FOLOTYN N=111
	All Grades (%)	Grade 3 (%)	Grade 4 (%)
Any Adverse Event	100	43	31
Mucositisa	70	17	4
Thrombocytopeniab	41	14	19b
Nausea	40	4	0
Fatigue	36	5	2
Anemia	34	15	2
Constipation	33	0	0
Pyrexia	32	1	1
Edema	30	1	0
Cough	28	1	0
Epistaxis	26	0	0
Vomiting	25	2	0
Neutropenia	24	13	7
Diarrhea	21	2	0
Dyspnea	19	7	0
Hypokalemia	15	4	1
Anorexia	15	3	0
Rash	15	0	0
Pruritus	14	2	0
Pharyngolaryngeal pain	14	1	0
Liver function test abnormalc	13	5	0
Abdominal pain	12	4	0
Pain in extremity	12	0	0
Leukopenia	11	3	4
Back pain	11	3	0
Night sweats	11	0	0
Asthenia	10	1	0
Upper respiratory tract infection	10	1	0
Tachycardia	10	0	0

aMucositis includes stomatitis or mucosal inflammation of the gastrointestinal and genitourinary tracts.

bFive patients with platelets < 10,000/mcL

cLiver function test abnormal includes increased ALT, increased AST, and increased transaminases

6.2 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of FOLOTYN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Dermatologic Reactions: Toxic epidermal necrolysis.