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Sylatron

"This week the U.S. Food and Drug Administration approved Mekinist (trametinib) in combination with Tafinlar (dabrafenib) to treat patients with advanced melanoma that is unresectable (cannot be removed by surgery) or metastatic (late-stage).

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Sylatron

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Depression and Other Serious Neuropsychiatric Adverse Reactions

Peginterferon alfa-2b can cause life-threatening or fatal neuropsychiatric reactions. These include suicide, suicidal and homicidal ideation, depression, and an increased risk of relapse of recovering drug addicts. In the clinical trial, depression occurred in 59% of SYLATRON-treated patients and 24% of patients in the observation group. Depression was severe or life threatening in 7% of SYLATRON-treated patients compared with < 1% of patients in the observation arm.

In post-marketing experience, neuropsychiatric adverse reactions have been reported up to 6 months after discontinuation of peginterferon alfa-2b. Based on post-marketing experience with peginterferon alfa-2b and interferon alfa­2b, treatment may also result in aggressive behavior, psychoses, hallucinations, bipolar disorders, mania, and encephalopathy.

Advise patients and their caregivers to immediately report any symptoms of depression or suicidal ideation to their healthcare provider. Monitor and evaluate patients for signs and symptoms of depression and other psychiatric symptoms every 3 weeks during the first 8 weeks of treatment and every 6 months thereafter. Monitor patients during treatment and for at least 6 months after the last dose of SYLATRON. Permanently discontinue SYLATRON for persistent severe or worsening psychiatric symptoms or behaviors and refer for psychiatric evaluation.

Cardiovascular Adverse Reactions

In the clinical trial, cardiac adverse reactions, including myocardial infarction, bundle-branch block, ventricular tachycardia, and supraventricular arrhythmia occurred in 4% of SYLATRON-treated patients compared with 2% of patients in the observation group. In post-marketing experience, hypotension, cardiomyopathy, and angina pectoris have occurred in patients treated with peginterferon alfa-2b.

Permanently discontinue SYLATRON for new onset of ventricular arrhythmia or cardiovascular decompensation.

Retinopathy and Other Serious Ocular Adverse Reactions

Peginterferon alfa-2b can cause decrease in visual acuity or blindness due to retinopathy. Retinal and ocular changes include macular edema, retinal artery or vein thrombosis, retinal hemorrhages and cotton wool spots, optic neuritis, papilledema, and serous retinal detachment may be induced or aggravated by treatment with peginterferon alfa-2b or other alpha interferons. In the clinical study, two SYLATRON-treated patients developed partial loss of vision due to retinal thrombosis (n=1) or retinopathy (n=1). The overall incidence of serious retinal disorders, visual disturbances, blurred vision, and reduction in visual acuity was < 1% in both SYLATRON-treated patients and the observation group.

Perform an eye examination that includes assessment of visual acuity and indirect ophthalmoscopy or fundus photography at baseline in patients with preexisting retinopathy and at any time during SYLATRON treatment in patients who experience changes in vision. Permanently discontinue SYLATRON in patients who develop new or worsening retinopathy.

Hepatic Failure

Peginterferon alfa-2b, increases the risk of hepatic decompensation and death in patients with cirrhosis. Monitor hepatic function with serum bilirubin, ALT, AST, alkaline phosphatase, and LDH at 2 and 8 weeks, and 2 and 3 months following initiation of SYLATRON, then every 6 months while receiving SYLATRON. Permanently discontinue SYLATRON for evidence of severe (Grade 3) hepatic injury or hepatic decompensation (Child-Pugh score > 6 [class B and C]) [see CONTRAINDICATIONS].

Endocrinopathies

Peginterferon alfa-2b can cause new onset or worsening of hypothyroidism, hyperthyroidism, and diabetes mellitus. In the clinical study, 1% of patients developed hypothyroidism; the overall incidence of endocrine disorders was 2% in SYLATRON-treated patients compared to < 1% for patients in the observation group.

Obtain TSH levels within 4 weeks prior to initiation of SYLATRON, at 3 and 6 months following initiation, then every 6 months thereafter while receiving SYLATRON. Permanently discontinue SYLATRON in patients who develop hypothyroidism, hyperthyroidism or diabetes mellitus that cannot be effectively managed.

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].
  • Instruct patients to not re-use or share syringes and needles.
  • Instruct patients on proper disposal of vials, syringes and needles.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis and Mutagenesis

SYLATRON has not been tested for its carcinogenic potential. Neither peginterferon alfa-2b nor its components, interferon or methoxypolyethylene glycol, caused damage to DNA when tested in the standard battery of mutagenesis assays, in the presence and absence of metabolic activation.

Impairment of Fertility

SYLATRON may impair human fertility. Irregular menstrual cycles were observed in female cynomolgus monkeys given subcutaneous injections of 4239 mcg/m² peginterferon alfa-2b alone every other day for 1 month (approximately 72 to 144 times the recommended weekly human dose based upon body surface area). These effects included transiently decreased serum levels of estradiol and progesterone, suggestive of anovulation. Normal menstrual cycles and serum hormone levels resumed in these animals 2 to 3 months following cessation of peginterferon alfa-2b treatment. Every other day dosing with 262 mcg/m² (approximately 3.5 to 7 times the recommended weekly human dose) had no effects on cycle duration or reproductive hormone status. The effects of SYLATRON on male fertility have not been studied.

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies of SYLATRON in pregnant women. Nonpegylated interferon alfa-2b was an abortifacient in Macaca mulatta (rhesus monkeys) at 15 and 30 million international units (IU)/kg (estimated human equivalent of 5 and 10 million IU/kg, based on body surface area adjustment for a 60-kg adult). The estimated Intron A human equivalent dose of 5 to 10 million IU/kg daily is approximately equal to a human equivalent dose of 79 to 158 mcg/kg/week of SYLATRON. Use SYLATRON during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether the components of SYLATRON are excreted in human milk. Studies in mice have shown that mouse interferons are excreted in breast milk. Because of the potential for adverse reactions from the drug in nursing infants, a decision must be made whether to discontinue nursing or discontinue the SYLATRON treatment, taking into account the importance of the therapy to the mother.

Pediatric Use

Safety and effectiveness in patients below the age of 18 years have not been established.

Geriatric Use

Clinical studies of SYLATRON did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Hepatic Impairment

SYLATRON has not been studied in patients with melanoma who have hepatic impairment. In patients treated for viral hepatitis, peginterferon alfa-2b treatment is contraindicated in those with moderate or severe hepatic impairment (Child-Pugh scores > 6). Discontinue SYLATRON if hepatic decompensation (Child-Pugh scores > 6) occurs during treatment. [See CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]

Renal Impairment

The mean area under the concentration-time curve (AUClast) following a single dose of peginterferon alfa-2b at 1 mcg/kg increased by 1.3-, 1.7- and 1.9-fold in subjects with mild (creatinine clearance 50-79 mL/min), moderate (creatinine clearance 30-50 mL/min) and severe (creatinine clearance 10-29 mL/min) renal impairment, respectively. After multiple doses, the mean AUCtau increased by 1.3-fold in moderate and 2.1-fold in severe renal impairment. No clinical meaningful amounts of peginterferon alfa-2b were removed during hemodialysis. Dose reductions of 25% and 50% are recommended in patients with moderate and severe renal impairment, respectively, receiving alpha interferons for chronic hepatitis C.

The effect of varying degrees of renal impairment on the pharmacokinetics of peginterferon alfa-2b at the recommended doses of 3 mcg/kg or 6 mcg/kg for patients with melanoma has not been studied.

Last reviewed on RxList: 1/23/2013
This monograph has been modified to include the generic and brand name in many instances.

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