Manufacturer:

Merck & Co., Inc.

Pharmacological Class:

Alpha interferon

Active Ingredient(s):

Peginterferon alfa-2b 296mcg, 444mcg, 888mcg; per vial; pwd for SC inj after reconstitution.

Indication(s):

Adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection including complete lymphadenectomy.

Pharmacology:

Peginterferon alfa-2b is a pleiotropic cytokine; the mechanism by which it exerts its effects in patients with melanoma is unknown.

Clinical Trials:

The safety and efficacy of Sylatron were evaluated in an open-label, multicenter, randomized study conducted in 1,256 patients with surgically resected, AJCC Stage III melanoma within 84 days of regional lymph node dissection. Patients were randomized to observation (no therapy) (n=629) or to Sylatron (n=627) at a dose of 6mcg/kg by SC injection once weekly for 8 doses followed by a 3mcg/kg SC injection once weekly for a period of up to 5 years total treatment. The dose of Sylatron was adjusted to maintain an ECOG Performance Status of 0 to 1. The main outcome measure was relapse-free survival (RFS), defined as the time from randomization to the earliest date of any relapse (local, regional, in-transit, or distant), or death from any cause. Secondary outcome measures included overall survival.

Based on 696 RFS events, determined by the Independent Review Committee, median RFS was 34.8 months and 25.5 months in the Sylatron and observation arms, respectively. There was no statistically significant difference in survival between the Sylatron and the observation arms.

Legal Classification:

Rx

Adults:

≥18yrs: Give by SC inj. Rotate inj sites. Premedicate with acetaminophen. 6mcg/kg/week for 8 doses, followed by 3mcg/kg/week for up to 5 years. Withhold dose if ANC <0.5x10⁹/L, platelets <50x10⁹/L, ECOG PS ≥2, or for non-hematologic toxicity ≥ Grade 3. Resume at reduced dose (see literature) when: ANC ≥0.5x10⁹/L, platelets ≥50x10⁹/L, ECOG PS 0–1, and non-hematologic toxicity has completely resolved or improved to Grade 1.

Children:

<18yrs: not recommended.

Contraindication(s):

Anaphylaxis to peginterferon alfa-2b or interferon alfa-2b. Autoimmune hepatitis. Hepatic decompensation (Child-Pugh score >6 [Class B and C]).

Warnings/Precautions:

Increased risk of neuropsychiatric disorders (eg, depression, suicidal ideation). Permanently discontinue for: persistent severe or worsening neuropsychiatric disorders (eg, depression, psychosis, encephalopathy); new onset ventricular arrhythmia, cardiovascular decompensation; new or worsening retinopathy; severe (Grade 3) hepatic injury or hepatic decompensation; hypothyroidism, hyperthyroidism, or diabetes mellitus that cannot be effectively managed; or if unable to tolerate a dose of 1mcg/kg/week. Monitor for signs/symptoms of depression/psychosis every 3 weeks during first 8 weeks, then every 6 months, continue for at least 6 months after last dose. Perform eye exam in patients with retinopathy and those with vision changes during therapy. Monitor hepatic function with serum bilirubin, ALT/AST, alkaline phosphate, and LDH at 2 and 8 weeks, and 2 and 3 months following initiation, then every 6 months. Obtain TSH levels within 4 weeks prior to initiation, at 3 and 6 months following initiation, then every 6 months. Pregnancy (Cat.C). Nursing mothers: not recommended.

Interaction(s):

Therapeutic effect of drugs metabolized by CYP2C9 or CYP2D6 may be altered.

Adverse Reaction(s):

Fatigue, increased ALT/AST, pyrexia, headache, anorexia, myalgia, nausea, chills, inj site reactions.

How Supplied:

Single-use vial—1, 4 (w. diluent)