peginterferon alfa 2b (PEG Intron, PegIntron Redipen, Sylatron)
Classes: Hepatitis B/Hepatitis C Agents
Dosing and uses of PEG Intron, Sylatron (peginterferon-alfa-2b)
Adult dosage forms and strengths
prefilled pen/vial (PegIntron Redipen, PEG Intron)
- 50mcg
- 80mcg
- 120mcg
- 150mcg
injectable powder with diluent (Sylatron)
- 296mcg/vial
- 444mcg/vial
- 888mcg/vial
Chronic Hepatitis C
Patients who are initiating therapy for HCV infection or who experienced relapse after prior PEG/RBV therapy, by HCV genotype (AASLD and IAS guidelines, April 2014)
Peginterferon is not recommended as monotherapy for any patient group
Genotypes 1, 4, 5, or 6
- Peginterferon alfa 2b + ribavirin + sofosbuvir (preferred regimen)
- 1.5 mcg/kg/Week SC; not to exceed 150 mcg/week, PLUS
- Ribavirin PO 1000-1200 mg/day (based on body weight) plus sofosbuvir 400 mg PO qDay
- Treat for 12 weeks (treatment-naive or relapsed); for nonresponders, may extend treatment of PEG/RBV to 24 weeks
- Reduce ribavirin dose if CrCl ≤50 mL/min
Alternative regimens
- Genotype 1: Simeprevir 150 mg/day x 12 weeks + PEG/RBV x 24 weeks
- Genotype 3: Sofosbuvir + PEG/RBV x 12 weeks
- Genotype 4: Simeprevir 150 mg/day x 12 weeks + PEG/RBV x 24-48 weeks
- Genotypes 5 and 6: PEG/RBV x 48 weeks
Melanoma (Sylatron)
Indicated for melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection including complete lymphadenectomy
6 mcg/kg/week SC for 8 doses, THEn
3 mcg/kg/week SC for up to 5 years
Renal Impairment
Dose reductions of 25% and 50% are recommended in patients with moderate and severe renal impairment, respectively, receiving alpha interferons for chronic hepatitis C
CrCl 30-50 mL/min: Reduce 25%
CrCl 10-29 mL/min (including HD): 50%
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
Hepatic Impairment
Peginterferon alfa-2b 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
Orphan Designations
Thrombocythemia
Myelofibrosis
Pediatric dosage forms and strengths
prefilled pen/vial (PegIntron Redipen, PEG Intron)
- 50mcg
- 80mcg
- 120mcg
- 150mcg
Chronic Hepatitis C
<3 years: Safety and efficacy not established
3-17 years: 60 mcg/m² SC qWeek (+ ribavirin 15 mg/kg/day PO divided q12hr); administer on same day each week
PEG Intron, Sylatron (peginterferon-alfa-2b) adverse (side) effects
>10% (Hepatitis C Trials)
Headache (56%)
Fatigue (52%)
Injection site inflammation/reaction (47%)
Depression (16-29%)
Anxiety/emotional lability/irritability (28%)
Nausea (26%)
Insomnia (23%)
Alopecia (22%)
Fever (22%)
Anorexia (20%)
Diarrhea (18%)
Abdominal pain (15%)
Dizziness (12%)
Impaired concentration (5-12%)
Pain (12%)
Pruritus (12%)
Dry skin (11%)
Weight loss (11%)
>10% (Melanoma Trials)
Fatigue (94%)
ALT or AST increased (77%)
Pyrexia (75%)
Headache (70%)
Anorexia (69%)
Myalgia (68%)
Nausea (64%)
Arthralgia (51%)
Chills (63%)
Injection site reactions (62%)
Depression (59%)
Dysgeusia (38%)
Diarrhea (37%)
Exfoliative rash (36%)
Dizziness (35%)
Alopecia (34%)
Vomiting (26%)
Olfactory nerve disorder (23%)
Blood alkaline phosphatase increased (23%)
Paraesthesia (21%)
Weight loss (11%)
1-10% (Hepatitis C Trials)
Pharyngitis (10%)
Transient increase in transaminases (10%)
Malaise (8%)
Dermatitis (7%)
Sinusitis (7%)
Vomiting (7%)
Dyspepsia (6%)
Flushing (6%)
Hepatomegaly (6%)
Rash (6%)
Hypertonia (5%)
Hypothyroidism (5%)
Injection site pain (2%)
Taste perversion
Neutropenia
Thrombocytopenia
1-10% (Melanoma Trials)
GGT increased (8%)
Proteinuria (7%)
Anemia (6%)
Dyspnea (6%)
Cough (5%)
<1% (Hepatitis C Trials)
Colitis
Pancreatitis
Autoimmune thrombocytopenia
Blindess, thrombosis of retinal vein
Aggressive behavior
Depression
Homicidal thoughts, suicidal thoughts, suicide
Frequency not defined
As with all proteins, there is a potential for immunogenicity
Postmarketing reports
Pulmonary fibrosis
Warnings
Black box warnings
Alfa interferons cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders
The risk of serious depression, with suicidal ideation and completed suicides, and other serious neuropsychiatric disorders are increased with alpha interferons
Discontinue drug if persistently severe or worsening signs or symptoms of the above conditions are present; disorders typically resolve after stopping therapy
These disorders may not resolve after the drug is discontinued
Monitored closely with periodic clinical and laboratory evaluations
Combination therapy with ribavirin
- Ribavirin may cause birth defects and/or fetal death
- Extreme care must be taken to avoid pregnancy in women taking peginterferon alfa-2a and in female partners of men taking peginterferon alfa-2a
- Ribavirin causes hemolytic anemia; associated anemia may result in worsening of cardiac disease
- Because ribavirin is genotoxic and mutagenic, consider it a potential carcinogen
Contraindications
Hypersensitivity
Autoimmune hepatitis
Decompensated liver disease (Child-Pugh >6 [class B and C])
Contraindications for combination therapy with ribavirin:
- Pregnant women and men whose female partners are pregnant
- Hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia)
- Creatinine clearance less than 50 mL/min
Cautions
May cause/aggravate fatal or life threatening autoimmune, ischemic, and infectious disorders
Life-threatening or fatal neuropsychiatric events, including suicide, suicidal and homicidal ideation, depression, relapse of drug addiction/overdose, and aggressive behavior sometimes directed towards others reported in patients with and without a previous psychiatric disorder during therapy and follow-up; psychoses, hallucinations, bipolar disorders, and mania have been observed in patients receiving this therapy and should be used with caution in patients with a history of psychiatric disorders; report any symptoms of depression or suicidal ideation to healthcare provider
Monitor and evaluate patients for signs and symptoms of depression and other psychiatric symptoms every 3 weeks during first 8 weeks of treatment and every 6 months thereafter; monitor patients during treatment and for at least 6 months after last dose; permanently discontinue therapy for suicidal or homicidal ideation, aggressive behavior towards others, or other severe or persistent psychiatric symptoms (see Black box warnings)
Caution with hypothyroidism, hyperthyroidism, hyperglycemia, and diabetes mellitus that cannot be effectively treated by medication
Cardiac adverse reactions occurred in 4% of patients during clinical trials; permanently discontinue with new onset ventricular arrhythmia or cardiovascular decompensation
Risk of visual impairment and retinal disorders; discontinue if ophthalmologic problems develop
Dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension, and sarcoidosis, some resulting in respiratory failure or patient deaths, may be induced or aggravated by therapy; recurrence of respiratory failure has been observed with interferon rechallenge; monitor
Ischemic and hemorrhagic cerebrovascular events observed
Development or exacerbation of autoimmune disorders (e.g., thyroiditis, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, rheumatoid arthritis, interstitial nephritis, systemic lupus erythematosus, and psoriasis) observed; use with caution in patients with autoimmune disorders
Pancreatitis and ulcerative or hemorrhagic/iscemic colitis may occur
Severe decreases in neutrophil or platelet counts reported
May cause birth defects and fetal death: use extreme care to avoid pregnancy in female patients and female partners of male patients
When administered in combination with ibavirin causes hemolytic anemia; associated anemia may result in worsening of cardiac disease
Hepatitis C (CHC) patients with cirrhosis may be at risk of hepatic decompensation and death when treated with alpha interferons, including peginterferon alpha 2b; cirrhotic CHC patients co-infected with HIV receiving highly active antiretroviral therapy (HAART) and alpha interferons with or without ribavirin appear to be at increased risk for development of hepatic decompensation compared to patients not receiving HAART; monitor clinical status and hepatic function during treatment and discontinue immediately if decompensation (Child-Pugh score greater than 6) observed
Monitor closely patients with impaired renal function, for signs and symptoms of interferon toxicity, including increases in serum creatinine; adjust dose or discontinue therapy accordingly
Serious, acute hypersensitivity reactions and cutaneous eruptions reported
Dental/periodontal disorders reported with combination therapy
Hypertriglyceridemia may result in pancreatitis (e.g., triglycerides greater than 1000 mg/dL)
Weight loss and growth inhibition reported during combination therapy in pediatric patients
Long-term growth inhibition (height) reported in some patients
Peripheral neuropathy observed when used in combination with telbivudine
Pregnancy and lactation
Pregnancy category: C
Lactation: Unknown if excreted in human milk; decide whether to discontinue drug or breastfeeding
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of PEG Intron, Sylatron (peginterferon-alfa-2b)
Mechanism of action
Immunomodulatory cytokine that enhances phagocytic activity of macrophages and cytotoxic activity of lymphocytes for target cells
Absorption
Half-life: 4.6 hr
Peak plasma time: 15-44 hr
Metabolism
Conjugation with polyethylene glycol slows metabolism
Elimination
Half-life: 40 hr
Excretion: Urine (30%)
Pharmacogenomics
A genetic variant near the gene encoding interferon-lambda-3 (IL28B rs12979860, a C to T change) is a strong predictor of response to peginterferon and ribavirin
Sustained virologic response rates tended to be lower with the C/T and T/T genotypes compared to those with the C/C genotype, particularly among previously untreated subjects receiving 48 weeks of peginterferon and ribavirin
Administration
SC Preparation (Sylatron)
Reconstitute with 0.7 mL sterile water for injection
Do not withdraw more than 0.5 mL of reconstituted solution from viaL
Resulting concentration following reconstitution
- 296 mg/vial = 40 mcg/0.1 mL
- 444 mg/vial = 60 mcg/0.1 mL
- 888 mg/vial = 120 mcg/0.1 mL
SC Administration
Once weekly dosing: Administer on same day each week
Rotate injection site