SYLATRON SIDE EFFECTS

Last updated on MDtodate: 10/12/2022

SIDE EFFECTS

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

• Depression and Other Neuropsychiatric Adverse Reactions
• Cardiovascular Adverse Reactions
• Retinopathy and Other Serious Ocular Adverse Reactions
• Hepatic Failure
• Endocrinopatliies

Clinical Trials Experience

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

The data described below reflect exposure to SYLATRON in 608 patients with surgically resected. AJCC Stage III melanoma. SYLATRON was studied in an open label, multicenter, randomized, observation controlled trial. The median age of the population was 50 years with 10% of patients 65 years or older, and 42% were female. Fourteen percent of patients completed the 5 year treatment schedule.

Patients randomized to SYLATRON were to receive total doses of 48 mcg/kg (6 mcg/kg subcutaneous once weekly for 8 doses), and 780 mcg/kg (3 mcg/kg subcutaneous once weekly until disease recurrence or for up to 5 years), as tolerated. The median total dose received was 42 mcg/kg (range: 6 to 78 mcg/kg) for the first 8 doses, and 136 mcg/kg (range: 1 to 774 mcg/kg) for doses 9 to 260.

Serious adverse events were reported in 199 (33%) patients who received SYLATRON and 94 (15%) patients in the observation group.

The most common adverse reactions experienced by SYLATRON-treated patients were fatigue (94%). increased ALT (77%). increased AST (77%). pyrexia (75%). headache (70%). anorexia (69%). myalgia (68%), nausea (64%), chills (63%), and injection site reaction (62%). The most common serious adverse reactions were fatigue (7%), increased ALT (3%). increased AST (3%), and pyrexia (3%) in the SYLATRON-treated group vs. <1% in the observation group for these reactions.

Thirty three percent of patients receiving SYLATRON discontinued treatment due to adverse reactions. The most common adverse reactions present at the time of treatment discontinuation were fatigue (27%), depression (17%), anorexia (15%), increased ALT (14%), increased AST (14%), myalgia (13%), nausea (13%), headache (13%), and pyrexia (11%). Adverse events that occurred in the clinical study at >5% incidence in the SYLATRON- treated group and with a greater incidence in patients receiving SYLATRON as compared to the observation group are presented in Table 1.

Table 1: Incidence of Adverse Reactions(*) Occurring in ≥5% of Melanoma Patients Treated with SYLATRON and with a Greater Incidence as Compared to Observation

Adverse Reaction	SYLATRON N=608		Observation N=628
	All Grades (%)	Grade 3 and 4 (%)	All Grades (%)	Grade 3 and 4 (%)
Any Adverse Reaction	100	51	82	18
General Disorders and Administrative Site Conditions
Fatigue	94	16	41	1
Pyrexia	75	4	9	0
Chills	63	1	6	0
Injection Site Reaction	62	1.8	0	0
Metabolic/Laboratory
ALT or AST Increased	77	11	26	1
Blood Alkaline Phosphatase Increased	23	0	11	<1
Weight Decreased	11	<1	1	<1
GGT Increased	8	4	1	<1
Proteinuria	7	0	3	0
Anemia	6	<1	2	<1
Nervous System Disorders
Headache	70	4	19	1
Dysgeusia	38	0	1	0
Dizziness	35	2	11	<1
Olfactory Nerve Disorder	23	0	1	0
Paraesthesia	21	<1	14	<1
Metabolism and Nutrition Disorders
Anorexia	69	3	13	0
Musculoskeletal and Connective Tissue Disorders
Myalgia	68	4	23	<1
Arthralgia	51	3	22	1
Gastrointestinal Disorders
Nausea	64	3	11	<1
Diarrhea	37	1	8	<1
Vomiting	26	1	4	0
Psychiatric Disorders
Depression	59	7	24	<1
Skin and Subcutaneous Tissue Disorders
Exfoliative Rash	36	1	4	0
Alopecia	34	0	1	0
Respiratory, Thoracic and Mediastinal Disorders
Dyspnea	6	1	2	1
Cough	5	<1	2	0
*Adverse reactions were graded using NCI CTCAE, V.2.0.

 

Immunogenieity

As with all therapeutic proteins, there is potential for immunogenieity. In a clinical study conducted in patients with melanoma, the incidence of binding antibodies to peg-interferon alfa-2b was approximately 35% (50/144 patients). Among the patients who tested positive for binding antibodies, one patient developed neutralizing antibodies. The impact of antibody formation on pharmacokinetics, safety and efficacy of peg-interferon alfa-2b could not be assessed based on limited available data.

The incidence of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to SYLATRON with the incidence of antibodies to other products may be misleading.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of peginterferon alfa-2b as monotherapy and in combination with ribavirin in chronic hepatitis C (CHC) patients. 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.

Blood and Lymphatic System Disorders

pure red cell aplasia, thrombotic thrombocytopenic purpura

Cardiac Disorders

pericarditis

Ear and Labyrinth Disorders

hearing loss, vertigo, hearing impairment

Endocrine Disorders

diabetic ketoacidosis

Eye Disorders

Vogt-Koyanagi-Harada syndrome

Gastrointestinal Disorders

aphthous stomatitis, pancreatitis, colitis, tongue pigmentation

Infusion Reactions

angioedema, urticaria, bronchoconstriction

Immune System Disorders

systemic lupus erythematosus, erythema multiforme, thyroiditis, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, rheumatoid arthritis, interstitial nephritis, and systemic lupus erythematosus

Infections

sepsis, hepatitis B virus reactivation in HCV/HBV co-infected patients

Metabolism and Nutrition Disorders

hypertriglyceridemia

Musculoskeletal and Connective Tissue Disorders

rhabdomyolysis, myositis

Nervous System Disorders

seizures, memory loss, peripheral neuropathy, paraesthesia, migraine headache

Respiratory, Thoracic and Mediastinal Disorders

dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, sarcoidosis, pulmonary hypertension, and pulmonary fibrosis

Skin and Subcutaneous Tissue Disorders

Stevens-Johnson syndrome, toxic epidermal necrolysis, psoriasis

Vascular Disorders

hypertension, hypotension, stroke