(in ter FEER on AL fa con one)
Treatment of chronic hepatitis C virus (HCV) infection in patients ≥18 years of age with compensated liver disease and anti-HCV serum antibodies or HCV RNA; concurrent use with ribavirin in HCV-infected patients who have failed treatment with pegylated interferon/ribavirin (Bacon, 2009)
Hypersensitivity to interferon alfacon-1 or any component of the formulation, other alpha interferons, or E. coli-derived products; decompensated liver disease (Child-Pugh class B and C); autoimmune hepatitis
Alpha interferons, including interferon alfacon-1, may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders.
Monitor patients closely with periodic clinical and laboratory evaluations. Patients with persistently severe or worsening symptoms of these conditions should be withdrawn from therapy. In many but not all cases, these disorders resolve after stopping interferon alfacon-1 therapy.
Use with ribavirin:Ribavirin may cause birth defects and/or death of the fetus. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin causes hemolytic anemia. The anemia associated with ribavirin therapy may result in a worsening of cardiac disease.
Note: Infergen has been discontinued in the US for more than 1 year.
Chronic HCV infection: SubQ: 9 mcg 3 times/week for 24 weeks; allow 48 hours between doses.
Combination therapy with ribavirin: SubQ: 15 mcg/day with ribavirin for up to 48 weeks
Patients who have previously tolerated interferon therapy but did not respond or relapsed: 15 mcg 3 times/week week for up to 48 weeks
Refer to adult dosing.
Not indicated for patients <18 years of age.
CrCl <50 mL/minute: Hepatitis C: Avoid combination therapy with ribavirin.
Use in decompensated hepatic disease (Child-Pugh class B or C) is contraindicated.
Interferon alfacon-1 is administered by SubQ injection, 3 times/week, with at least 48 hours between doses. Allow to reach room temperature just prior to administration.
Store in refrigerator 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F); do not freeze. Avoid exposure to direct sunlight. Do not shake vigorously.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Injectable, Subcutaneous [preservative free]:
Infergen: 9 mcg/0.3 mL (0.3 mL [DSC]); 15 mcg/0.5 mL (0.5 mL [DSC])
Aldesleukin: Interferons (Alfa) may enhance the adverse/toxic effect of Aldesleukin. In particular, risks of myocardial and renal toxicity may be increased by this combination. Consider therapy modification
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Methadone: Interferons (Alfa) may increase the serum concentration of Methadone. Monitor therapy
Ribavirin (Oral Inhalation): Interferons (Alfa) may enhance the adverse/toxic effect of Ribavirin (Oral Inhalation). Hemolytic anemia has been observed. Monitor therapy
Ribavirin (Systemic): Interferons (Alfa) may enhance the adverse/toxic effect of Ribavirin (Systemic). Hemolytic anemia has been observed. Monitor therapy
Theophylline Derivatives: Interferons may decrease the metabolism of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy
Zidovudine: Interferons may enhance the adverse/toxic effect of Zidovudine. Interferons may decrease the metabolism of Zidovudine. Monitor therapy
Hemoglobin and hematocrit; white blood cell count; platelets; triglycerides; thyroid function. Laboratory tests should be taken prior to therapy, 2 weeks after therapy has begun, and periodically during treatment. HCV RNA, ALT to determine success/response to therapy.
The following guidelines were used during the clinical studies as acceptable baseline values:
Platelet count ≥75 x 109/L
Hemoglobin ≥100 g/L
ANC ≥1500 x 106/L
Scr <180 micromole/L (<2 mg/dL) or CrCl >0.83 mL/second (>50 mL/minute)
Serum albumin ≥25 g/L
Bilirubin ≤1.4 mg/dL (except for patients with Gilbert 's syndrome)
TSH and T4 WNL
Patients should also be monitored for signs of depression. Patients with pre-existing diabetes mellitus or hypertensive retinopathy should have a baseline ophthalmic exam and periodic exams during therapy.
Adverse reactions reported using 9 mcg/dose interferon alfacon-1 3 times/week. Flu-like symptoms (which included headache, fatigue, fever, myalgia, rigors, arthralgia, and increased diaphoresis) were the most commonly reported adverse reaction; this was reported separately from flu-like syndrome.
>10%:
Cardiovascular: Chest pain (13%)
Central nervous system: Headache (82%), fatigue (69%), fever (61%), insomnia (39%), nervousness (31%), depression (26%), dizziness (22%), anxiety (19%), emotional lability (12%), malaise (11%)
Dermatologic: Alopecia (14%), pruritus (14%), rash (13%)
Endocrine & metabolic: Hot flashes (13%)
Gastrointestinal: Abdominal pain (41%), nausea (40%), diarrhea (29%), anorexia (24%), dyspepsia (21%), vomiting (12%)
Hematologic: Granulocytopenia (23%), thrombocytopenia (3% to 19%), leukopenia (15%)
Local: Injection site erythema (23%)
Neuromuscular & skeletal: Myalgia (58%), rigors (57%), body pain (54%), arthralgia (51%), back pain (42%), limb pain (26%), neck pain (14%), skeletal pain (14%), paresthesia (13%)
Respiratory: Pharyngitis (34%), upper respiratory tract infection (31%), cough (22%), sinusitis (17%), rhinitis (13%), respiratory tract congestion (12%)
Miscellaneous: Flu-like syndrome (15%), diaphoresis increased (12%)
1% to 10%:
Cardiovascular: Peripheral edema (9%), hypertension (5%), tachycardia (4%), palpitation (3%)
Central nervous system: Amnesia (10%), hypoesthesia (10%), abnormal thinking (8%), agitation (6%), confusion (4%), somnolence (4%), apathy (2%), hyperesthesia (1%)
Dermatologic: Bruising (6%), erythema (6%), dry skin (6%), wound (4%)
Endocrine & metabolic: Thyroid test abnormalities (9%), dysmenorrhea (9%), triglycerides increased (6%), menstrual disorder (6%), decreased libido (5%), hypothyroidism (4%), menorrhagia (3%)
Gastrointestinal: Constipation (9%), flatulence (8%), toothache (7%), salivation decreased (6%), hemorrhoids (6%), weight loss (5%), taste perversion (3%), stomatitis (3%), gingivitis (2%)
Genitourinary: Vaginitis (8%), genital moniliasis (2%)
Hematologic: Hematocrit decreased (5%), hemoglobin decreased (4%), anemia (1% to 2%)
Hepatic: Liver tenderness (5%), hepatomegaly (3%), prothrombin time increased (3%)
Local: Injection site pain (9%), access pain (8%), injection site bruising (6%)
Neuromuscular & skeletal: Weakness (9%), hypertonia (7%), musculoskeletal disorder (4%)
Ocular: Conjunctivitis (8%), eye pain (5%), vision abnormalities (3%)
Otic: Tinnitus (6%), earache (5%), otitis (2%)
Respiratory: Upper respiratory tract congestion (10%), epistaxis (8%), dyspnea (7%), bronchitis (6%)
Miscellaneous: Allergic reaction (7%), lymphadenopathy (6%), lymphocytosis (5%), infection (3%)
<1% (limited to important or life-threatening): Abdominal distension, abnormal gait, arthritis, ascites, ataxia, autoimmune disorders exacerbated, bone pain, cerebrovascular hemorrhage, cerebrovascular ischemia, creatinine increased, dehydration, delusion, diabetes, gastritis, gastrointestinal bleeding, hallucinations, hearing impairment, hearing loss, hemorrhage, hemorrhagic/ischemic colitis, hepatic encephalopathy, hepatic function abnormal, hepatotoxicity (idiosyncratic) (Chalasani, 2014), hyperbilirubinemia, hyperglycemia, hypersensitivity, injection site necrosis, injection site ulcer, jaundice, loss of consciousness, memory impairment, pancreatitis, pyoderma gangrenosum, renal failure, rhabdomyolysis, seizure, sepsis, speech disorder, tachyarrhythmias, toxic epidermal necrolysis, transaminases increased, tremor, visual field defect
Concerns related to adverse effects:
- Bone marrow suppression: Causes bone marrow suppression, including potentially severe cytopenias; discontinue for ANC <500/mm3and platelets <25,000/mm3. Use with caution in patients with low peripheral blood counts or myelosuppression, including concurrent use of myelosuppressive therapy. May worsen when used in combination with ribavirin; use caution in patients with ANC <1500/mm3.
- Cardiovascular events: Hypotension, palpitations, tachycardia, and tachyarrhythmias have been reported with interferon alfacon-1use. Alfa interferon treatment has been associated with supraventricular arrhythmias, chest pain and MI. Use with caution in patients with pre-existing cardiac disease.
- Flu-like symptoms: Commonly associated with flu-like symptoms, including fever; rule out other causes/infection with persistent or high fever.
- Gastrointestinal effects: Gastrointestinal hemorrhage, ulcerative and hemorrhagic/ischemic colitis have been observed with interferon alfa treatment, including alfacon-1; may be severe and/or life-threatening; discontinue if symptoms (eg, abdominal pain, bloody diarrhea, and/or fever) develop.
- Hypersensitivity: Acute hypersensitivity reactions have been reported (rarely) with alfa interferons.
- Nephrotoxicity: Increases in serum creatinine and (rarely) renal failure have been reported with use; monitor closely for signs/symptoms of toxicity.
- Neuropsychiatric disorders: [U.S. Boxed Warning]: May cause severe psychiatric adverse events (eg, depression, psychosis, mania, suicidal behavior/ideation) in patients with and without previous psychiatric symptoms; use with extreme caution in patients with a history of depression. Careful neuropsychiatric monitoring is required during therapy. Patients developing severe depression may require discontinuation of treatment. Although dose reduction or discontinuation may resolve symptoms, depression may persist; suicides have been reported after therapy with alfa interferons has been discontinued. Use with caution in patients with seizure disorders, brain metastases, or compromised CNS function.
- Ocular effects: Decreased/loss of vision, retinopathy (including macular edema), retinal artery or vein thrombosis, retinal hemorrhages, cotton wool spots, optic neuritis, papilledema, and retinal detachment have occurred in patients receiving other alpha interferons. Use caution in patients with pre-existing ophthalmic disorders; monitor closely and discontinue with new or worsening ophthalmic symptoms. Visual exams are recommended for patients with diabetes mellitus or hypertensive retinopathy.
- Pancreatitis: Has been observed (occasionally fatal); hypertriglyceridemia increases the risk for pancreatitis; discontinue treatment in patients with confirmed pancreatitis.
- Peripheral neuropathy: May occur in combination with telbivudine; interrupt treatment for suspected peripheral neuropathy and discontinue if confirmed; symptoms may be reversible with discontinuation.
- Pulmonary effects: Dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonia, pulmonary hypertension, and sarcoidosis, resulting in potential fatal respiratory failure may occur with interferon alfa treatment, including interferon alfacon-1. Discontinue with unexplained pulmonary infiltrates or evidence of impaired pulmonary function. Use caution in patients with a history of pulmonary disease.
Disease-related concerns:
- Autoimmune disease: [U.S. Boxed Warning]: Avoid use in patients with history of autoimmune disorders. Development or exacerbation of autoimmune disorders (thrombocytopenic purpura, vasculitis, Raynaud 's disease, rheumatoid arthritis, interstitial nephritis, thyroiditis, lupus erythematosus, and rhabdomyolysis) has been associated with interferon alfa. Monitor closely and consider discontinuing if autoimmune disease develops. Use is contraindicated in patients with autoimmune hepatitis.
- Diabetes: Use with caution in patients with diabetes mellitus; hyperglycemia has been reported which may require adjustments in medications. Discontinue interferon alfacon-1 if unable to control blood sugars with medication during treatment.
- Hepatic impairment: Use with caution in patients with hepatic impairment; may be at risk for hepatic decompensation with alfa interferon therapy. Monitor closely; discontinue with signs (eg, jaundice, ascites, coagulopathy, hypoalbuminemia) of hepatic decompensation.
- Hepatitis C (chronic): Not for use as monotherapy; concurrent use with ribavirin.
- Infectious disorders: [U.S. Boxed Warning]: May cause or aggravate fatal or life-threatening infectious disorders; discontinue treatment for persistent severe or worsening symptoms.
- Ischemic disorders: [U.S. Boxed Warning]: May cause or aggravate fatal or life-threatening ischemic disorders; discontinue treatment for persistent severe or worsening symptoms.
- Renal impairment: Use with caution in patients with renal impairment; interferon alfacon-1 has not been studied in these patients. Monitor closely. Combination therapy with ribavirin (hepatitis C) should not be used in patients with reduced renal function (CrCl <50 mL/minute).
- Thyroid disorders: Use with caution in patients with pre-existing thyroid disease; thyroid disorders (hyper- or hypothyroidism) have been reported. Discontinue interferon alfacon-1 if unable to control thyroid disorders with medication during treatment.
Concurrent drug therapy issues:
- Combination therapy with ribavirin: [U.S. Boxed Warning]: Combination treatment with ribavirin may cause birth defects and/or fetal mortality; hemolytic anemia (which may worsen cardiac disease), and may possibly be carcinogenic.
Special populations:
- Immunocompromised patients: Use with caution in chronically-immunosuppressed patients, including transplantation recipients.
Dosage form specific issues:
- Product variability: Due to differences in dosage, patients should not change brands of interferons without the concurrence of their healthcare provider.
C
There have been no well-controlled studies in pregnant women. Animal studies have shown embryolethal or abortifacient effects. Males and females who are being treated with interferon alfacon-1 should use effective contraception.
Interferon alfacon-1 is a member of the alpha interferon family of proteins, which are produced by nucleated cells, and have antiviral, antiproliferative, and immune-regulating activity. Interferons interact with cells through high affinity cell surface receptors. Following activation, multiple effects can be detected. Interferons induce gene transcription, inhibit cellular growth, alter the state of cellular differentiation, interfere with oncogene expression, alter cell surface antigen expression, increase phagocytic activity of macrophages, and augment cytotoxicity of lymphocytes for target cells. Although all alpha interferons share similar properties, the actual biological effects vary between subtypes.
Healthy volunteers: 24-36 hours
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience dyspepsia, nausea, diarrhea, alopecia, insomnia, arthralgia, myalgia, lack of appetite, headache, hot flashes, injection site irritation, or flu-like symptoms. Have patient report immediately to prescriber signs of bowel problems (black, tarry, or bloody stools; fever; mucus in stools; vomiting; vomiting blood; severe abdominal pain; constipation; or diarrhea), signs of a pancreas problem (pancreatitis; severe abdominal pain, severe back pain, severe nausea, vomiting), signs of a severe pulmonary disorder (lung or breathing problems like trouble breathing, shortness of breath, or a cough that is new or worse), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of infection, signs of depression (suicidal ideation, anxiety, emotional instability, illogical thinking, hallucination, psychosis, suicidal ideation), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight), severe dizziness, passing out, angina, tachycardia, arrhythmia, urinary retention, change in amount of urine passed, bruising, bleeding, burning or numbness feeling, vision changes, blindness, memory impairment, difficulty focusing, temperature sensitivity, weight gain or loss, or skin irritation (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.