Interferon alfacon-1 Side Effects
Applies to interferon alfacon-1: injectable solution
A broad range of serious side effects have been reported with interferon alfacon-1, alone or in combination with ribavirin. During clinical trials, more than 560 and 480 patients were exposed to monotherapy and combination therapy, respectively. In monotherapy studies, influenza-like symptoms (i.e., headache, fatigue, fever, rigors, myalgia, arthralgia, and increased sweating) were reported most often and depression was the most common side effect resulting in drug discontinuation. In the interferon alfacon-1 plus ribavirin combination therapy study, fatigue, nausea, influenza-like symptoms, headache, arthralgia, myalgia, neutropenia, leukopenia, insomnia, and depression were the most commonly reported side effects and fatigue, anemia, and depression were the most common side effects resulting in drug discontinuation. The most common serious adverse reactions reported with combination therapy were neutropenia, suicidal ideation, and hyperuricemia.[Ref]
Other side effects have included fatigue (up to 77%), rigors (up to 66%), fever/pyrexia (up to 61%), body pain (up to 54%), influenza-like illness/symptoms (up to 42%), chest pain (up to 13%), malaise (up to 11%), asthenia (up to 10%), hot flushes, peripheral edema, access pain, earache, taste perversion, and otitis.[Ref]
Nervous system side effects have included headache (up to 82%), insomnia (up to 39%), dizziness (up to 25%), paresthesia (up to 13%), hypoesthesia (up to 10%), amnesia (up to 10%), hypertonia, somnolence, taste perversion, confusion, tinnitus, and hyperesthesia. Ischemic and hemorrhagic cerebrovascular events have been reported. Vestibular side effects associated with interferon alfacon-1 have been mild and infrequent. Hearing loss, hearing impairment, speech disorder, ataxia, gait abnormal, convulsions, loss of consciousness, memory impairment, and tremors have been reported during postmarketing experience.[Ref]
Gastrointestinal side effects have included nausea (up to 45%), abdominal pain (up to 41%), diarrhea (up to 29%), anorexia (up to 24%), dyspepsia (up to 21%), vomiting (up to 19%), decreased appetite (up to 18%), constipation (up to 10%), flatulence, toothache, decreased saliva output, ulcerative stomatitis, hemorrhoids, and gingivitis. Hemorrhagic/ischemic colitis (sometimes fatal) and pancreatitis (sometimes fatal) have been reported. Abdominal distention, gastrointestinal bleeding, and gastritis have been reported during postmarketing experience.[Ref]
Higher doses of interferon alfacon-1 were associated with a greater incidence of leukopenia and granulocytopenia and required dose reductions in 33% of patients receiving secondary therapy.
Decreases from baseline of 20% or more in hemoglobin or hematocrit were reported in less than or equal to 1% of patients during monotherapy trials. During the combination interferon alfacon-1 plus ribavirin trial, decreases in hemoglobin levels of greater than or equal to 2 g/dL from baseline were reported in 88% of patients. Of these, 27% had hemoglobin levels decrease to less than or equal to 10 g/dL, and underwent dose reductions of ribavirin.
By the end of initial monotherapy treatment, mean decreases from baseline of 19% for white blood cells (WBCs) and 23% for absolute neutrophil count (ANC) were reported. In patients subsequently retreated with monotherapy, mean decreases from baseline up to 23% for WBCs and up to 27% for ANC were reported.
Decreases in mean platelet count of 16% compared to baseline were observed by the end of monotherapy. Grade 4 thrombocytopenia was reported in one patient during the alfacon-1 plus ribavirin combination trial.[Ref]
Hematologic side effects have included leukopenia (up to 34%), neutropenia, thrombocytopenia, granulocytopenia, anemia, lymphocytosis, ecchymosis, lymphadenopathy, and increased prothrombin time. Decreases in hemoglobin (monotherapy: 4%; combination therapy: 88%), hematocrit (monotherapy: 5%), total white blood cell count, absolute neutrophil count (ANC), and platelet count have been reported. Hemolytic anemia (30%), ANC levels less than 0.75 x 10(9)/L (up to 27%), and lymphopenia (up to 14%) have been reported during combination therapy with ribavirin. Platelets decreased to less than 50 x 10(9) cells/L in 3% of patients during monotherapy and to less than 40 x 10(9)/L (but not less than 25 x 10(9)/L) in up to 3% of patients during combination therapy with ribavirin. Hemorrhage has been reported during postmarketing experience.[Ref]
Psychiatric side effects have included nervousness (up to 31%), depression (up to 27%), irritability (up to 21%), abnormal thinking (up to 20%), anxiety (up to 19%), emotional lability (up to 12%), agitation, decreased libido, and apathy. Delusions and hallucinations have been reported during postmarketing experience.[Ref]
Depression was usually mild to moderate in severity in patients receiving interferon alfacon-1 therapy during clinical studies.[Ref]
Musculoskeletal side effects have included myalgia (up to 58%), arthralgia (up to 51%), back pain (up to 42%), limb pain (up to 26%), skeletal pain (up to 14%), neck pain (up to 14%), and musculoskeletal disorder. Rhabdomyolysis, arthritis, and bone pain have been reported during postmarketing experience.
Cardiovascular side effects have included hypotension, arrhythmia, tachycardia, cardiomyopathy, angina pectoris, and myocardial infarction. Palpitation and hypertension have been reported. At least one case of irreversible pulmonary artery hypertension has been reported.[Ref]
A 36-year-old male with a history of intravenous drug use and alcoholism experienced irreversible pulmonary artery hypertension coincident with interferon alfacon-1 therapy. He was treated with interferon alfa-2a (3 million units/day) after he was found to have cirrhosis from Hepatitis C virus (HCV) and alcohol use. His viral load was 100,000 copies of stage IV fibrosis on liver biopsy. He was cleared of virus and received a liver transplant. Subsequently, he again became HCV positive (greater than 85,000 copies/mL) and was treated with interferon alfacon-1 (15 mcg/kg). Eight months into therapy, he developed progressive dyspnea on exertion, fatigue, and edema. He was found to have severe pulmonary hypertension on echocardiogram (PAP 81/30) with right heart failure. Other thromboembolic, inflammatory, and intrinsic cardiopulmonary causes were ruled out and interferon treatment was discontinued. He continues to experience severe refractory pulmonary hypertension.[Ref]
Ocular side effects have included conjunctivitis, abnormal vision, and eye pain. Decrease or loss of vision, retinopathy (including macular edema, retinal artery or vein thrombosis, retinal hemorrhages, cotton wool spots), optic neuritis, papilledema, and serous retinal detachment have been induced or aggravated by treatment with interferon alfacon-1. Retinal artery or vein obstruction has been reported rarely. Visual field defect has been reported during postmarketing experience.[Ref]
Immunologic side effects have included development of positive binding antibody responses (up to about 31%), development of low-titer neutralizing antibodies to interferon alfacon-1 (up to 18%), and infection. Development or exacerbation of autoimmune disorders (e.g., autoimmune thrombocytopenia, idiopathic thrombocytopenia purpura, psoriasis, rheumatoid arthritis, thyroiditis, interstitial nephritis, systemic lupus erythematosus) has been reported. Sepsis has been reported during postmarketing experience.
Local side effects have included injection site erythema (up to 23%), injection site reaction (up to 15%), pain, and ecchymosis. Injection site reaction, including injection site necrosis ulcer, and bruising have been reported during postmarketing experience.[Ref]
Metabolic side effects have included decreased weight (up to 22%), increased triglyceride levels (up to 7%), hypertriglyceridemia, hyperglycemia, and diabetes mellitus. Grade 4 uric acid levels (greater than 10 mg/dL) were reported in 49 patients during combination therapy with ribavirin. Dehydration has been reported during postmarketing experience.
Increases in serum triglyceride of 41% compared to baseline were observed at the end of monotherapy. During monotherapy treatment, 7% of patients developed values at least 3 times above pretreatment levels. Grade 3 or higher triglyceride elevations were reported in 2% of patients during the alfacon-1 plus ribavirin combination trial.
Serious adverse events related to elevated uric acid levels were reported in 4 patients during the alfacon-1 plus ribavirin combination trial.
Respiratory side effects have included pharyngitis (up to 34%), cough (up to 22%), dyspnea (up to 20%), sinusitis (up to 17%), upper respiratory infection, rhinitis, respiratory tract congestion, upper respiratory tract congestion, epistaxis, and bronchitis.
Dermatologic side effects have included rash (up to 17%), pruritus (up to 15%), alopecia (up to 14%), increased sweating (up to 13%), erythema, dry skin, and wound. Bruising, pyoderma gangrenosum, and toxic epidermal necrolysis have been reported during postmarketing experience.
Endocrine side effects have included the occurrence or aggravation of hyperthyroidism or hypothyroidism. Abnormal thyroid function tests with increases in thyroid stimulating hormone (TSH) and decreases in thyroxine (T4) mean values have been reported. Increased TSH to greater than 7 mU/L was reported in 10% of patients treated with monotherapy during the treatment period or during the 24-week posttreatment period. During the interferon alfacon-1 plus ribavirin combination trial, increased TSH levels were reported in up to 14% of patients at Week 12 and up to 54% at Week 48.[Ref]
Renal side effects have included increases in serum creatinine levels (including renal failure).
Hepatic side effects have included liver tenderness and hepatomegaly. Hepatic enzyme elevations (including ALT and AST elevations), abnormal hepatic function, hyperbilirubinemia, jaundice, ascites, and hepatic encephalopathy have been reported during postmarketing experience.[Ref]
Genitourinary side effects have included dysmenorrhea, vaginitis, menstrual disorder, menorrhagia, genital moniliasis, breast mass, and breast pain.
1. "Product Information. Infergen (interferon alfacon-1)." Amgen, Thousand Oaks, CA.
2. Dhillon S, Baluch M, George M, Van Thiel DH "Irreversible pulmonary artery hypertension during interferon-alpha therapy for HCV infection: a case report." Am J Gastroenterol 98(9S) (2003): S179-S180
3. Kleppinger EL, Ragan AP "Elevated hepatic transaminases associated with the use of interferon alfacon-1 and ribavirin." Am J Health Syst Pharm 66 (2009): 465-8
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Some side effects may not be reported. You may report them to the FDA.