discontinue Folotyn [see Adverse Reactions (6.2) and Use in Specific Populations (8.7)].
Tumor Lysis Syndrome
Folotyn can cause tumor lysis syndrome (TLS). Monitor patients who are at increased risk of TLS and treat promptly.
Hepatic Toxicity
Folotyn can cause hepatic toxicity and liver function test abnormalities. Persistent liver function test abnormalities may be indicators of hepatic toxicity and require dose modification or discontinuation. Monitor liver function tests. Omit dose until recovery, adjust or discontinue therapy based on the severity of the hepatic toxicity [see Dosage and Administration (2.2) and Use in Specific Populations (8.6)].
5.6 Risk of Increased Toxicity in the Presence of Impaired Renal Function
Patients with moderate to severe renal function impairment may be at greater risk for increased exposure and toxicity. Monitor patients for renal function and systemic toxicity and adjust dosing accordingly.
Serious adverse drug reactions including toxic epidermal necrolysis and mucositis were reported in patients with end stage renal disease (ESRD) undergoing dialysis who were administered Folotyn therapy. Avoid Folotyn use in patients with end stage renal disease including those undergoing dialysis unless the potential benefit justifies the potential risk [see Dosage and Administration (2.2), Adverse Reactions (6.2), Use in Specific Populations (8.7), and Clinical Pharmacology (12.3)].
Embryo-Fetal Toxicity
Folotyn can cause fetal harm when administered to a pregnant woman. Folotyn was embryotoxic and fetotoxic in rats and rabbits. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1)].
Adverse Reactions
The following serious adverse reactions are described below and elsewhere in the labeling:
•Bone Marrow Suppression [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)]
The most common adverse reactions observed in patients with peripheral T-cell lymphoma (PTCL) treated with Folotyn were mucositis, thrombocytopenia, nausea, and fatigue.
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.
The safety of Folotyn was eva luated in 111 PTCL patients in a single-arm clinical study in which patients received a starting dose of 30 mg/m2 once weekly for 6 weeks in 7-week cycles. The median duration of treatment was 70 days (range 1-540 days).
Most Frequent Adverse Reactions
Table 4 summarizes the most frequent adverse reactions, regardless of causality, using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE, version 3.0).
Table 4 Adverse Reactions Occurring in PTCL Patients (Incidence ≥ 10% of patients) N=111
Total Grade 3 Grade 4
Preferred Term N % N % N %
aStomatitis or mucosal inflammation of the gastrointestinal and genitourinary tracts.
bFive patients with platelets < 10,000/m |
