Peginterferon Alfa-2b

Pronunciation: peg-IN-ter-FEER-on AL-fa
Class: Immunomodulator

Trade Names

PegIntron
- Injection, lyophilized powder for solution 50 mcg per 0.5 mL (reconstituted)
- Injection, lyophilized powder for solution 80 mcg per 0.5 mL (reconstituted)
- Injection, lyophilized powder for solution 120 mcg per 0.5 mL (reconstituted)
- Injection, lyophilized powder for solution 150 mcg per 0.5 mL (reconstituted)

PegIntron Redipen
- Injection, lyophilized powder for solution 50 mcg per 0.5 mL (reconstituted)
- Injection, lyophilized powder for solution 80 mcg per 0.5 mL (reconstituted)
- Injection, lyophilized powder for solution 120 mcg per 0.5 mL (reconstituted)
- Injection, lyophilized powder for solution 150 mcg per 0.5 mL (reconstituted)

Sylatron
- Injection, lyophilized powder for solution 40 mcg per 0.1 mL (reconstituted)
- Injection, lyophilized powder for solution 60 mcg per 0.1 mL (reconstituted)
- Injection, lyophilized powder for solution 120 mcg per 0.1 mL (reconstituted)

Unitron PEG (Canada)

Pharmacology

Binds to specific membrane receptors on cell surface and initiates a complex sequence of intracellular events (eg, suppression of cell proliferation, enhancement of phagocytic activity of macrophages).

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Pharmacokinetics

Absorption

T max is 15 to 44 h ( PegIntron ). Bioavailability increases with multiple dosing. C max ranges from 2.5 to 4.4 ng/mL ( Sylatron ).

Elimination

Renal excretion is 30%. The elimination half-life is approximately 40 h ( PegIntron ) and 43 to 51 h ( Sylatron ). Apparent Cl is 22 mL/h•kg ( PegIntron ).

Duration

Duration is 48 to 72 h ( PegIntron ).

Special Populations

Renal Function Impairment

PegIntron Cl decreases by 17% in patients with moderate renal impairment (CrCl 30 to 49 mL/min) and by 44% in those with severe renal impairment (CrCl 10 to 29 mL/min). Reduce dose in patients with moderate or severe renal impairment. The effects of varying degrees of renal impairment on the pharmacokinetics of peginterferon alfa-2b at doses recommended for patients with melanoma have not been studied.

Elderly

Pharmacokinetics were similar in patients older than 65 y when compared with younger patients (28 to 44 y of age) ( PegIntron ).

Children

In children receiving PegIntron 60 mcg/m 2 /wk, exposure may be approximately 50% higher than that observed in adults receiving 1.5 mcg/kg/wk.

Gender

No differences were observed in the pharmacokinetic profiles of men and women with chronic hepatitis C infection.

Indications and Usage

For use alone in the treatment of chronic hepatitis C virus (HCV) in patients 18 y and older not previously treated with interferon alfa who have compensated liver disease ( PegIntron ); in combination with ribavirin for the treatment of chronic HCV in patients 3 y and older who have compensated liver disease ( PegIntron ); adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection, including complete lymphadenectomy ( Sylatron ).

Unlabeled Uses

Treatment of renal cell carcinoma, chronic myelogenous leukemia, metastatic melanoma.

Contraindications

Autoimmune hepatitis; decompensated liver disease (Child-Pugh score greater than 6 [class B and C]); hypersensitivity to peginterferon alfa-2b, interferon alfa-2b, or any component of the product.

PegIntron/Ribavirin capsules combination

Hypersensitivity to ribavirin capsules or any other component of the product; women who are pregnant; men whose female partners are pregnant; patients with hemoglobinopathies (eg, thalassemia major, sickle-cell anemia); CrCl less than 50 mL/min.

Dosage and Administration

Chronic Hepatitis C
PegIntron Monotherapy Adults

Subcutaneous 1 mcg/kg/wk for 1 y. For patients weighing 45 kg or less, administer 40 mcg; 46 to 56 kg, administer 50 mcg; 57 to 72 kg, administer 64 mcg; 73 to 88 kg, administer 80 mcg; 89 to 106 kg, administer 96 mcg; 107 to 136 kg, administer 120 mcg; 137 to 160 kg, administer 150 mcg.

PegIntron Dose in Combination Therapy With Ribavirin Adults

Subcutaneous 1.5 mcg/kg/wk. For patients weighing less than 40 kg, administer 50 mcg; 40 to 50 kg, administer 64 mcg; 51 to 60 kg, administer 80 mcg; 61 to 75 kg, administer 96 mcg; 76 to 85 kg, administer 120 mcg; 86 to 105 kg, administer 150 mcg; more than 105 kg, calculate dose based on individual patient weight.

Children 3 to 17 y of age

Subcutaneous 60 mcg/m 2 /wk.

Melanoma ( Sylatron )
Adults

Subcutaneous 6 mcg/kg/wk subcutaneously for 8 doses, followed by 3 mcg/kg/wk subcutaneously for up to 5 y.

Dose Reduction

Subcutaneous If a serious adverse reaction occurs during treatment, discontinue or modify the dosage until the adverse event abates or decreases in severity. If persistent or recurrent serious adverse events occur despite adequate dosage adjustments, discontinue treatment. See product information for guidelines for dosage modification or discontinuation in adults and children.

Renal Function Impairment ( PegIntron )
Adults and Children 3 y and older Moderate renal function impairment (CrCl 30 to 50 mL/min)

Subcutaneous Decrease the peginterferon alfa-2b dose 25%.

Severe renal function impairment (CrCl 10 to 29 mL/min), including patients on hemodialysis

Subcutaneous Decrease the peginterferon alfa-2b dose 50%.

If renal function decreases during treatment, discontinue peginterferon alfa-2b. Do not use peginterferon alfa-2b/ribavirin combination therapy in patients with CrCl less than 50 mL/min. In children, if creatinine is more than 2 mg/dL, permanently discontinue peginterferon alfa-2b and ribavirin capsules.

General Advice

  • For subcutaneous administration only. Not for intradermal, IM, IV, or intra-arterial administration. Rotate injection sites.
  • Administer dose at bedtime to minimize flu-like symptoms.
  • Administer antipyretics as pretreatment to minimize flu-like symptoms.
  • Reconstitute powder for injection in vials or Redipen following manufacturer's instructions.
  • Do not reconstitute with any solution other than that provided with the powder for injection; do not add any other medication to reconstituted solution.
  • Do not shake solution during reconstitution process. Gently invert Redipen or gently swirl contents in vial to obtain a clear, colorless solution.
  • Use only 1 dose per vial or pen. Do not re-enter vial. Discard any unused portions. Do not save unused solution for later administration.
  • In patients with HCV genotype 1, the duration of combination therapy is 48 weeks; in patients with HCV genotype 2 or 3, the duration of combination therapy is 24 weeks.

Storage/Stability

Store unopened vials between 59° and 86°F. Store Redipen in the refrigerator (36° to 46°F). Administer reconstituted solution immediately or store for up to 24 h in refrigerator. Do not freeze.

Drug Interactions

Didanosine

Fatal hepatic failure, as well as peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/lactic acidosis have been reported in patients receiving didanosine and ribavirin. Ribavirin, with or without peginterferon alfa-2b, should not be coadministered with didanosine.

Drugs metabolized by CYP2C8/9 (eg, phenytoin, warfarin) or CYP2D6 (eg, flecainide)

Plasma concentrations of these substrates may be reduced by peginterferon alfa-2b, decreasing the pharmacologic effects. Evaluate the response of the patient and adjust the dose of the substrate as needed.

Methadone

Methadone plasma concentrations may be elevated, increasing the narcotic effect. Monitor patients for signs and symptoms of increased narcotic effect and adjust the methadone dose as needed.

Nucleoside reverse transcriptase inhibitors

In patients receiving nucleoside reverse transcriptase inhibitors (NRTIs) and peginterferon alfa-2b with or without ribavirin, closely monitor for treatment-associated toxicities (eg, hepatic decompensation, anemia), especially in HIV/HCV coinfected patients with cirrhosis. Discontinue the NRTI as medically appropriate. Reduce the dose or discontinue interferon, ribavirin, or both if toxicities develop.

Pyrimidine nucleoside analogs (eg, lamivudine, stavudine, zidovudine)

Severe neutropenia and severe anemia may develop in HIV/HCV coinfected patients receiving pyrimidine nucleoside analogs and peginterferon alfa-2b with ribavirin. Closely monitor the patient.

Telbivudine

Peripheral neuropathy has been reported when alpha interferons were given in combination with telbivudine. Coadminister with caution.

Adverse Reactions

The incidences stated for the following adverse reactions were reported with peginterferon alfa-2b monotherapy.

Cardiovascular

Hypertension, hypotension, palpitations, stroke (postmarketing).

CNS

Fatigue (94%); headache (70%); depression (59%); asthenia or fatigue (52%); dizziness (35%); anxiety, emotional lability, irritability (28%); insomnia (23%); paresthesia (21%); irritability (14%); impaired concentration (10%); malaise (7%); nervousness (4%); agitation (2%); homicidal ideation, memory loss, migraine headache, peripheral neuropathy, seizures, vertigo (postmarketing).

Dermatologic

Exfoliative rash (36%); alopecia (34%); pruritus (12%); dry skin (11%); flushing, increased sweating, rash (6%); erythema multiforme, psoriasis, Stevens-Johnson syndrome, TEN (postmarketing).

EENT

Olfactory nerve disorder (23%); pharyngitis (10%); conjunctivitis (4%); blurred vision, rhinitis (2%); hearing loss, impaired hearing, serous retinal detachment, Vogt-Koyanagi-Harada syndrome (postmarketing).

GI

Anorexia (69%); nausea (64%); dysgeusia (38%); diarrhea (37%); vomiting (26%); abdominal pain (15%); dry mouth, dyspepsia (6%); constipation (1%); aphthous stomatitis, colitis, pancreatitis (postmarketing).

Genitourinary

Proteinuria (7%); menstrual disorder (4%); interstitial nephritis, renal failure, renal insufficiency (postmarketing).

Hematologic-Lymphatic

Decreased neutrophils (70%); decreased platelets (20%); leukopenia (10%); thrombocytopenia (7%); anemia, neutropenia (6%); idiopathic thrombocytopenic purpura, pure red cell aplasia, thrombotic thrombocytopenic purpura (postmarketing).

Hepatic

ALT or AST increased (77%); increased blood alkaline phosphatase (23%); GGT increased (8%); hepatomegaly (6%).

Hypersensitivity

Cases of acute hypersensitivity reactions, including anaphylaxis, angioedema, bronchoconstriction, and urticaria (postmarketing).

Local

Injection-site reaction (62%).

Metabolic-Nutritional

Weight loss (11%); hypothyroidism (5%); dehydration, diabetes, diabetic ketoacidosis, hypertriglyceridemia, thyroiditis (postmarketing).

Musculoskeletal

Myalgia (68%); arthralgia (51%); musculoskeletal pain (28%); rigors (23%); myositis, rhabdomyolysis, rheumatoid arthritis (postmarketing).

Respiratory

Coughing (8%); sinusitis (7%); dyspnea (6%); bronchiolitis obliterans, interstitial pneumonitis, pneumonia, pulmonary hypertension, pulmonary infiltrates, sarcoidosis (postmarketing).

Miscellaneous

Pyrexia (75%); chills (63%); viral infection (11%); right upper quadrant pain (8%); chest pain (6%); bacterial infection including sepsis, SLE (postmarketing).

Precautions

Warnings

PegIntron Neuropsychiatric, autoimmune, ischemic, and infectious disorders

Interferons may cause or aggravate fatal or life-threatening disorders of this nature. Persistent, severe, or worsening signs or symptoms may necessitate discontinuation of therapy. Closely monitor patients with periodic clinical and laboratory evaluations.

Use with ribavirin

Ribavirin may cause birth defects and fetal death. Extreme care must be taken to avoid pregnancy in women and in female partners of men. Ribavirin causes hemolytic anemia, which may result in worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen.

Sylatron Depression and other neuropsychiatric disorders

The risk of serious depression, with suicidal ideation and completed suicides, and other serious neuropsychiatric disorders is increased with alpha interferons. Permanently discontinue peginterferon alfa-2b in patients with persistently severe or worsening signs or symptoms of depression, psychosis, or encephalopathy. These disorders may not resolve after stopping peginterferon alfa-2b.


Monitor

Monitor hepatic function with serum bilirubin, ALT, AST, alkaline phosphatase, and LDH at 2- and 8-week intervals, and 2 and 3 months following initiation of therapy, then every 6 months while receiving treatment. Closely monitor patients with renal impairment for peginterferon toxicity, including increases in serum creatinine. Hematology and blood chemistry should be evaluated before treatment, at weeks 2 and 4 of therapy, and periodically thereafter. Patients with preexisting cardiac abnormalities should have an ECG done before treatment. Patients should have regular dental checkups. All patients should receive an eye exam prior to the start of therapy and periodically thereafter in patients with diabetic or hypertensive retinopathy. Monitor blood glucose more frequently in patients with diabetes. Monitor patients for worsening depression, suicidal thoughts or ideation, aggressive behavior, or other psychiatric symptoms every 3 weeks during first 8 weeks of treatment, and every 6 months thereafter; also monitor for these symptoms for at least 6 months after the last dose. Obtain TSH levels within 4 wk prior to initiation of treatment, at 3 and 6 months following initiation, then every 6 months.

Hepatitis C virus levels

Determine HCV levels before starting therapy and after 12 and 24 weeks of therapy. Be prepared to discontinue therapy in patients who do not achieve a 2 log 10 drop or loss of HCV-RNA at 12 weeks, or if HCV-RNA remains detectable after 24 weeks of therapy.


Pregnancy

Category C ; Category X when used with ribavirin.

Lactation

Undetermined. Interferon alfa is excreted in breast milk; the American Academy of Pediatrics classifies interferon alfa as compatible with breast-feeding.

Children

Safety and efficacy not established in children younger than 3 y ( PegIntron ). Safety and efficacy not established in children ( Sylatron ).

Elderly

Use with caution.

Hypersensitivity

Serious, acute hypersensitivity reactions (eg, angioedema, anaphylaxis) and cutaneous eruptions (eg, Stevens-Johnson syndrome, TEN) may occur with alpha interferon therapy.

Renal Function

Use with caution and monitor for signs and symptoms of interferon toxicity. Reduce dose in patients with moderate or severe renal impairment ( PegIntron ). Increases in serum creatinine have occurred in patients with renal insufficiency.

Hepatic Function

Patients with chronic hepatitis C with cirrhosis may be at risk of hepatic decompensation and death. Immediately discontinue treatment if decompensation occurs.

Autoimmune disorders

Because interferon alfa may cause or exacerbate autoimmune disorders (eg, thyroiditis, SLE), use with caution in patients with history of autoimmune disorders. Discontinue use in patients with persistently severe or worsening signs or symptoms.

Bone marrow toxicity

Bone marrow function may be suppressed, sometimes resulting in severe cytopenias.

Cardiovascular events

Use with caution in patients with CV disease, including hypotension, arrhythmia, tachycardia, cardiomyopathy, and MI.

Cerebrovascular disorders

Ischemic and hemorrhagic cerebrovascular events have been reported. Events have occurred in patients with few or no reported risk factors.

Colitis

Fatal and nonfatal ulcerative or hemorrhagic/ischemic colitis has been observed. Discontinue use immediately in patients who develop symptoms.

Dental and periodontal disorders

Dental and periodontal disorders have been reported.

Endocrine disorders

Hypo- and hyperthyroidism may occur or be aggravated. Hyperglycemia and diabetes mellitus have been observed in treated patients.

Immunogenicity

Development of binding and/or neutralizing antibodies to peginterferon alfa-2b may occur.

Neuropsychiatric events

Because life-threatening or fatal neuropsychiatric events, including suicide, suicidal and homicidal ideation, depression, relapse of drug addiction, and aggressive behavior, have occurred, use with caution, especially in patients with a history of psychiatric disorder. Discontinue use in patients with persistently severe or worsening signs or symptoms.

Ophthalmic disorders

Decrease in or loss of vision, retinal hemorrhages, cotton wool spots, retinopathy (including macular edema), and retinal artery or vein thrombosis have been observed.

Pancreatitis

Fatal and nonfatal pancreatitis has been observed. Discontinue use in patients who develop symptoms.

Pediatric growth

Weight and height gain in children treated with PegIntron plus ribavirin lags behind that compared with normative population data. After approximately 6 months posttreatment, study subjects had weight gain rebounds and regained their weight to the 53rd percentile. After approximately 6 months posttreatment, height gain stabilized and children had an average height in the 44th percentile, which is less than the average normative population.

Pulmonary disorders

Dyspnea, pulmonary infiltrates, pneumonia, interstitial pneumonitis, pulmonary hypertension, and sarcoidosis, some resulting in respiratory failure and/or patient deaths, have been associated with use.

Triglycerides

Elevated triglyceride levels may occur.

Overdosage

Symptoms

Headache, myalgia, neutropenia, severe fatigue, thrombocytopenia.

Patient Information

  • Review Medication Guide with the patient. Ensure that the patient understands how to store, prepare, and administer the dose, and dispose of used equipment and supplies.
  • Remind patient that prescribed dose is administered once weekly and to administer on the same day of the week.
  • Caution patients not to change the dose or stop taking peginterferon alfa-2b unless advised by their health care provider.
  • Advise patient that dose may be reduced or the medication stopped if it causes depression or significant changes in blood cell counts.
  • Teach patient infection control and bleeding precautions.
  • Advise patient that it is not known if this drug will prevent transmission of hepatitis C to others, nor is it known if it can prevent cirrhosis, liver failure, or liver cancer that may develop as a result of hepatitis C infection.
  • Instruct patients to immediately report any of the following to their health care provider: signs or feelings of depression and/or suicidal ideation, fever, sore throat, unusual bleeding or bruising, stomach pain, bloody diarrhea, rapid or irregular pulse, difficulty breathing or unexplained shortness of breath.
  • Advise women of childbearing potential and female partners of men during therapy to use effective contraception during treatment and for 6 months posttreatment.
  • Advise patients to brush their teeth thoroughly twice daily and to have regular dental examinations.
  • Advise patients that flu-like symptoms associated with peginterferon alfa-2b administration may be minimized by administration at bedtime or by use of antipyretics.

Copyright © 2009 Wolters Kluwer Health.

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