SYLATRON- peginterferon alfa-2b
Merck Sharp & Dohme Corp.
WARNING: DEPRESSION AND OTHER NEUROPSYCHIATRIC DISORDERS
The risk of serious depression, with suicidal ideation and completed suicides, and other serious neuropsychiatric disorders are increased with alpha interferons, including SYLATRON. Permanently discontinue SYLATRON in patients with persistently severe or worsening signs or symptoms of depression, psychosis, or encephalopathy. These disorders may not resolve after stopping SYLATRON [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)].
1 INDICATIONS AND USAGE
SYLATRON� is an alpha interferon indicated for the adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection including complete lymphadenectomy.
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dosing
The recommended starting dose is 6 mcg/kg/week subcutaneously for 8 doses, followed by 3 mcg/kg/week subcutaneously for up to 5 years.
Premedicate with acetaminophen 500 to 1000 mg orally 30 minutes prior to the first dose of SYLATRON and as needed for subsequent doses.
The recommended starting doses of SYLATRON in patients with moderate or severe renal impairment or end-stage renal disease (ESRD) are listed in Table 1 [see Use in Specific Populations (8.7)]. No dose adjustment is needed for patients with a creatinine clearance (CLcr) > 50 mL/min/1.73m2.
3 DOSAGE FORMS AND STRENGTHS
200 mcg of deliverable lyophilized powder per single-use vial
300 mcg of deliverable lyophilized powder per single-use vial
600 mcg of deliverable lyophilized powder per single-use vial
4 CONTRAINDICATIONS
SYLATRON is contraindicated in patients with:
A history of anaphylaxis to peginterferon alfa-2b or interferon alfa-2b
autoimmune hepatitis
hepatic decompensation (Child-Pugh score >6 [class B and C])
DESCRIPTION
SYLATRON, peginterferon alfa-2b, is a covalent conjugate of recombinant alfa-2b interferon with monomethoxy polyethylene glycol (PEG). The average molecular weight of the PEG portion of the molecule is 12,000 daltons. The average molecular weight of the SYLATRON molecule is approximately 31,000 daltons. The specific activity of pegylated interferon alfa-2b is approximately 0.7 � 108 international units/mg protein.
Interferon alfa-2b is a protein with a molecular weight of 19,271 daltons produced by recombinant DNA techniques. It is obtained from the bacterial fermentation of a strain of Escherichia coli bearing a genetically engineered plasmid containing an interferon gene from human leukocytes.
Each vial contains either 296 mcg, 444 mcg or 888 mcg of peginterferon alfa-2b as a sterile, white to off-white lyophilized powder, and dibasic sodium phosphate anhydrous (1.11 mg), monobasic sodium phosphate dihydrate (1.11 mg), polysorbate 80 (0.074 mg), and sucrose (59.2 mg).
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Peginterferon alfa-2b is a pleiotropic cytokine; the mechanism by which it exerts its effects in patients with melanoma is unknown.
PATIENT COUNSELING INFORMATION
See FDA-approved patient labeling (Instructions for Use and Medication Guide).
Advise patients that SYLATRON may be administered with antipyretics at bedtime to minimize common �flu-like" symptoms (including chills, fever, muscle aches, joint pain, headaches, tiredness).
Advise patients to maintain hydration if experiencing �flu-like" symptoms.
Advise patients and their caregivers to immediately report any symptoms of depression or suicidal ideation to their healthcare provider during treatment and up to 6 months after the last dose.
Use SYLATRON during pregnancy only if the potential benefit justifies the potential risk to the fetus [see Use in Specific Populations (8.1)].
Instruct patients to not re-use or share syringes and needles.
Instruct patients on proper disposal of vials, syringes and needles.
Advise patients that the Sterile Water for Injection vials supplied contain an excess amount of diluent and only 0.7 mL should be withdrawn to reconstitute SYLATRON. Discard the unused portion of sterile water. Do not save or reuse.