interferon alfa 2b (Intron A, Interferon alfa-2b)
Classes: Hepatitis B/Hepatitis C Agents; Biological Response Modifiers
Dosing and uses of Intron A, Interferon alfa-2b (interferon alfa 2b)
Adult dosage forms and strengths
injectable solution
- 6 million International Units/mL (3.8mL vial)
- 10 million International Units/mL (3.2mL vial)
multidose pen; 6 doses each
- 22.5 million International Units/1.5mL
- 37.5 million International Units/1.5mL
- 75 million International Units/1.5mL
powder for injection
- 10 million International Units/vial
- 18 million International Units/vial
- 50 million International Units/vial
Hairy Cell Leukemia
2 million Units/m² IM/SC 3 times/wk for up to 6 mo
If severe adverse reaction (ADR) develop: reduce dose by 50% or temporarily withhold, THEn
Resume at 50% after ADRs abate: 1 million Units/m² IM/SC 3 times/wk
If severe ADRs persist discontinue permanently
Discontinue Intron A for progressive disease or failure to respond after 6 mo of treatment
Malignant Melanoma
Induction 20 million Units/m² IV over 20 min, 5 days/wk for 4 wk
Maintenance dose: 10 million Units/m² SC 3 times/wk for 48 wk
Withhold treatment if ANC <500/mm³ or ALT/AST >5 times upper limit of normal (ULN); re-start at 50% previous dose
Permanently discontinue if the following is observed
- Toxicity does not abate after withholding
- Severe ADRs recur in patients receiving reduced doses
- ANC <250/mm³ or ALT/AST >10x ULN
Follicular Lymphoma
5 million units 3 times/week for up to 18 mo in conjunction with anthracycline-containing combination chemotherapy in patients >18 years old
See Mfr's prescribing packet for additional chemo dosing information
Condylomata Acuminata
1 million units injected into each lesion 3 times/week qODay for 3week
May repeat course if unsatisfactory results 12-16 wk after initial treatment
Max 5 lesions/single course of treatment
Do not use the 18 or 50 million Units powder for injection
Do not use the 18 million Units multidose Intron A solution for injection
Do not use multidose pens
AIDS-related Kaposi's Sarcoma
30 million Units/m² IM/SC 3 times/wk for 16 wk
Dose reduction frequently required: See Mfr's PI
Chronic Hepatitis C
3 million units IM/SC 3 times/wk for16 wk
If ALT normalized after 16 wk, continue treatment for 18-24 mo
If ALT not normalized or high levels of HCV RNA after 16 wk, consider discontinuing treatment
Acute Hepatitis C
5 million Units SC/IM qd for 4 wk, then 3 times/wk for 20 wk
If severe adverse reactions develop reduce dose by 50% or temporarily withhold until adverse reactions abate
If intolerance persists discontinue permanently
Chronic Hepatitis B
30-35 million Units SC/IM per wk, either as 5 million Units qDay or 10 millon Units 3 times/wk for 16 wk
Reduce 50%: WBC <1.5 x 10^9/L; Granulocyte <0.75 x 10^9/L; platelets <50 x 10^9/L
Discontinue permanently: WBC < 1.0 x 10^9/L; Granulocyte <0.5 x 10^9/L; platelet < 25 x 10^9/L
If severe adverse reactions develop reduce dose by 50% or temporarily withhold until adverse reaction abate
If intolerance persists discontinue permanently
Other Information
Monitor: LFTs, CBC, platelets, Hgb, Electrolytes, TSH
See also combo with ribavirin
Pediatric dosage forms and strengths
injectable solution
- 6 million International Units/mL (3.8mL vial)
- 10 million International Units/mL (3.2mL vial)
multidose pen; 6 doses each
- 22.5 million International Units/1.5mL
- 37.5 million International Units/1.5mL
- 75 million International Units/1.5mL
powder for injection
- 10 million International Units/vial
- 18 million International Units/vial
- 50 million International Units/vial
Chronic Hepatitis B
3 million Units/m² IM/SC 3 times/wk for 1 wk; increase to 6 million U/m² 3 times/wk SC for 16-24 wk; not to exceed 10 million Units/dose 3 times/wk
Dose adjustments: See manufacturer's package insert
Intron A, Interferon alfa-2b (interferon alfa 2b) adverse (side) effects
>10%
Fatigue (8-96%)
Fever (34-94%)
Neutropenia (92%)
Flu-like syndrome (79%)
Myalgia (28-75%)
Anorexia (1-69%)
Leukopenia (68%)
Nausea (17-66%)
Transaminases increased (13-63%)
Weakness (63%)
Headache (21-62%)
Chills (54%)
Diarrhea (2-45%)
Rigors (42%)
Depression (up to 40% of pts), suicidal ideation/ attempts, suicide
Alopecia (38%)
Dyspnea (34%)
Somnolence (33%)
Vomiting (2-32%)
Anemia (32%)
Cough (31%)
Pharyngitis (31%)
Chest pain (28%)
Xerostomia (28%)
Rash (25%)
Dizziness (24%)
Taste alteration (24%)
Abdominal pain (1-23%)
Irritability (22%)
Sinusitis (21%)
Skeletal pain (21%)
Diaphoresisi (1-21%)
Paresthesias (1-21%)
Arthralgia/back pain (19%)
Pain (18%)
Moniliasis (17%)
Thrombocytopenia (15%)
Amnesia (14%)
Constipation (14%)
Gingivitis (14%)
Impaired concentration (14%)
Malaise (14%)
Weight loss (1-13%)
Amenorrhea (12%)
BUN increased (12%)
Confusion (12%)
Insomnia (12%)
Iruritus (11%)
1-10%
Bronchitis (10%)
Dry skin (10%)
Edema (10%)
Hypoestheisa (10%)
Loose stools (10%)
Nasal congestion (10%)
Polyuria (10%)
Anxiety (9%)
Hypertension (9%)
Dermatitis (8%)
Dyspepsia (8%)
Vertigo (8%)
Agitation (7%)
Infection (7%)
SCr increased (6%)
Herpes virus infections (5%)
UTI (5%)
<1%
Acute hypersensitivity reactions; exacerbation of preexisting psoriasis & sarcoidosis
Myelosuppression, thyroid dysfunction, hepatotox., pulmonary infiltrates, retinal hemorrhage
Severe cytopenias incl aplastic anemia
Autoimmune dz, DM/hyperglycemia (rare)
Posmarketing 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
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 treated with interferon alpha should be used with caution in patients with a history of psychiatric disorders; discontinue if severe depression develops
If psychiatric symptoms persist or worsen, or suicidal or homicidal ideation or aggressive behavior towards others identified, discontinue therapy and follow patient closely, with psychiatric intervention as appropriate; narcotics, hypnotics, or sedatives may be used concurrently with caution and patients should be closely monitored until adverse effects resolved
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
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
Caution in pre-existing cardiac abnormalities &/or advanced cancer Ischemic and hemorrhagic cerebrovascular events reported
Pancreatitis and ulcerative or hemorrhagic/iscemic colitis may occur
Severe decreases in neutrophil or platelet counts reported
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 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
Risk of visual impairment and retinal disorders; discontinue if ophthalmologic problems develop
Use with caution in patients with endocrine disorder: thyroid disease; DM prone to ketoacidosis
Pre-existing cardiac abnormalities &/or advanced cancer
AIDS-related Kaposi's Sarcoma: do not use in patients w/ rapidly progressive disease
Discontinue if acute hypersensitivity occurs
Risk of exacerbation of preexisting psoriasis & sarcoidosis; risk of developing new sarcoidosis
Patients should be well hydrated during initial treatment
If platelets <50,000/mm³, do not administer IM (may admin SC)
Do not use the 18 million IU or 50 million IU powder for injection or the18 million IU multidose vial for condylomata acuminata
Increases risk of hepatic decompensation and death in patients with cirrhosis; any patient developing liver function abnormalities during treatment should be monitored closely and if appropriate, treatment should be discontinued
Numerous cardiotoxicities, including arrhythmias, ischemia, infarction, and cardiomyopathy occur during and immediately after infusion
Pregnancy and lactation
Pregnancy category: C
Lactation: unknown
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 Intron A, Interferon alfa-2b (interferon alfa 2b)
Mechanism of action
Inhibits HBV replication; immunomodulatory actions; may induce gene transcription; interferes with oncogene expression, may change cell surface antigen expressoin; cytotoxic activity of macrophages increases
Suppresses cell proliferation
Pharmacokinetics
Half-Life: 2-3 hr (IM/SC); 2 hr (IV)
Peak Plasma Time: 3-12 hr (IM/SC); 30 min (IV)
Pharmacogenomics
Polymorphic cytokine genes (encoding IL-10, a Th2 cytokine); Th2 responses are associated with production of large amounts of antibodies
Patients with chronic hepatitis C are 5 times more likely to have a favorable response to interferon alfa if they carried the IL-10 genetic polymorphism that results in low expression of IL-10 than if they did not
Administration
IV Preparation
GeneraL
- Reconstitute vials with provided diluent
- Preparation should be clear & colorless to light yellow
IM, SC, or Intralesional Preparation
- Inject 1 mL diluent (SWI, supplied) into drug vial
- Swirl gently to dissolve powder
- Withdraw appropriate dose to be injected
- Refer to Medication Guide for detailed instructions
IV Administration
- Prepare immediately prior to use
- Reconstitute w/ diluent provided
- Inject 1 mL diluent (SWI, supplied) into drug vial
- Swirl gently to dissolve powder
- Withdraw appropriate dose & inject into a 100 mL bag of NS
- Make sure final conc of Intron A is NOT <10 MIU/100 mL
- Refer to Medication Guide for detailed instructions
Intron A Solution for Injection not recommended for IV
SC Administration
SC administration is suggested for those who are at risk for bleeding or thrombocytopenic
Rotate SC injection site
Storage
Refrigerate intact vials
Powder & premixed solutions are stable at room temp for 7 d & for 30 d if refrigerated
