Interferons adverse effects

A single intramuscular dose of recombinant human interferon alfa-2a 18 million units was given to 8 healthy subjects alone, or after one day of either aspirin 650 mg every 4 hours, paracetamol 650 mg every 4 hours or prednisone 40 mg daily, for a total of 8 days. None of these additional drugs reduced the interferon adverse effects of fever, chills, headache, or myalgia. Only prednisone appeared to reduce one of the two measures of interferon activity. In a later similar study by the same research group, the effect of the same drugs and doses (started 3 days before the interferon) was evaluated with a lower dose of interferon alfa-2a (3 million units). When data for aspirin, paracetamol or prednisone was combined the... 

At present, pegylated interferon plus ribavirin is the regimen of choice for the treatment of hepatitis C.41 Interferon, pegylated interferon, and ribavirin have significant adverse effects, as discussed below. 

The type and incidence of adverse effects associated with unmodified interferon and pegylated interferon are comparable. Approximately 10% to 30% of patients receiving interferon and/or ribavirin require a dosage reduction or treatment discontinuation to minimize side effects. Patients should be screened for uncommon adverse effects and laboratory abnormalities prior to starting interferon and ribavirin because treatment may exacerbate or worsen some medical conditions. 

Psychiatric adverse effects occur frequently and may include irritability, depression, and rarely, suicidal ideation. Individuals with a history of uncontrolled psychiatric disorders must weigh the risk versus benefit of treatment, as interferon may exacerbate or worsen the psychiatric condition. Patients who develop mild to moderate symptoms may require antidepressants or anxiolytics. Those with severe symptoms including suicidal ideation should have the treatment discontinued immediately.43... 

While there are no FDA-approved treatments for hepatitis D, interferon has been shown to be effective.46 48 Various doses have been evaluated, with the most effective treatment being 9 million units three times weekly.47 Seventy-one percent of patients who were treated with this regimen for 48 weeks had normalized ALT levels.47 Adverse effects and monitoring parameters for interferon therapy are similar to treatment for hepatitis C. In some situations, patients infected with hepatitis D who develop hepatic decompensation and ESLD may need to undergo liver transplantation. 

Assess for adverse effects in patients with hepatitis C treated with interferon or pegylated interferon with or without ribavirin. 

Adverse effects of interferon, pegylated interferon, and ribavirin therapy... 

Adverse Effects Adverse effects are common with the beta interferons (Table 26-3). Commonly, flulike symptoms consist of fever, fatigue, muscle aches, malaise, and chills. Symptoms begin a few hours after the injection and dissipate 8 to 24 hours later.38 Preventive measures can be employed (Table 26-4). In temperature-sensitive patients, beta interferon-induced fever... 

Bayas A, Reickmann R Managing the adverse effects of interferon-(3 therapy in multiple sclerosis. Drug Saf 2000 22 149-159. 

Another perceived view about Western drugs is the adverse effects. Western medicine is sometimes viewed as a sledgehammer method rather than the more holistic approach using TM. The costs of Western medicine can be prohibitive as well, especially for patients in countries where there are no comprehensive healthcare systems. For example, treatment with pegylated interferon for hepatitis C or antibody for colon cancer can cost tens of thousands of dollars per year. Limitations of Western drugs in some cases, such as resistance to antibiotics, also highlight problems and pave the way for people to consider TM. See Exhibit 11.3 on how GlaxoSmithKline and... 

Elderly Treatment with alpha interferons, including peginterferon alfa-2b, is associated with CNS, cardiac, and systemic (flu-like) adverse effects. Because these adverse reactions may be more severe in the elderly, exercise caution in the use of interferon alfa-2b in this population. 

Furthermore, not all patients respond positively to a specific drug (e.g. interferon-)S is of clinical benefit to only one in three multiple sclerosis patients see Chapter 4). The range and severity of adverse effects induced by a drug can also vary significantly within a patient population base. 

The most frequent adverse effects are flu-like symptoms increased body temperature, feeling ill, fatigue, headache, muscle pain, convulsion, dizziness, hair thinning and depression. Erythema, pain and hardness on the spot of injection are also frequently observed. Interferon therapy may cause immunosuppression. Also various interferon induced autoimmune syndromes were reported. 

Interferon gamma is an activator of macrophages. Its anti-viral activity is limited compared to that of interferon alfa. Human recombinant interferon gamma restores, at least in part, macrophage cytotoxicity and with that decreases the incidence of infections in patients with chronic granulomatous diseases. Its adverse effects consist mainly of flu-like syndrome skin rashes may occur. 

Adverse effects of such regimes are common, thus interferons can cause anorexia, influenza-like illness, myelosuppression, and cardiovascular, hepatic and renal adverse effects. 

Interferons are associated with a diverse range of common adverse effects. CNS complaints such as... 

The adverse effects of interferon alfa-2b include fever and a fiulike syndrome of muscle ache, fatigue, headache, anorexia, and nausea. Other less common side effects include leukopenia, diarrhea, dizziness, and skin rash. 

Since the original 1988 report of hypothyroidism in patients with breast cancer receiving leukocyte-derived interferon alfa (498), numerous investigators have provided clear clinical and biological data on thyroid disorders induced by different forms of interferon in patients with various diseases (499,500-503). Two of these reports also mentioned associated adverse effects that developed concomitantly, namely myelosuppression and severe proximal myopathy (Hoffmann s syndrome). 

A middle-aged woman developed subacute thyroiditis by the sixth month of treatment with interferon alfa (508). She also had the classic symptoms of hyperthyroidism, although it is clear that these could easily have been mistaken for adverse effects of interferon alfa itself, for example weakness, weight loss, and palpitation. 

Severe hypertriglyceridemia, a well-known adverse effect of interferon beta, has been reported and fully investigated in a 39-year-old man receiving interferon beta for chronic hepatitis C (563). 

Drug(s) Biologic response modifiers Interferons Interferon alfa-2a [Roferon-A] Interferon alfa-2b [Intron-A] Primary Antineoplastic Indication(s) Hairy-cell leukemia Kaposi sarcoma chronic myelocytic leukemia renal and bladder cancers Common Adverse Effects Flulike syndrome [mild fever, chills, malaise]... 

Typical side effects are constitutional in nature, including a flu-like syndrome within 6 hours after dosing in more than 30% of patients that tends to resolve upon continued administration. Other potential adverse effects include thrombocytopenia, granulocytopenia, elevation in serum aminotransferase levels, induction of autoantibodies, nausea, fatigue, headache, arthralgias, rash, alopecia, anorexia, hypotension, and edema. Severe neuropsychiatric side effects may occur. Absolute contraindications to therapy are psychosis, severe depression, neutropenia, thrombocytopenia, symptomatic heart disease, decompensated cirrhosis, uncontrolled seizures, and a history of organ transplantation (other than liver). Alfa interferons are abortifacient in primates and should not be administered in pregnancy. 

Because the type I interferons produced no adverse effects on embryofetal development and the early abortifacient effect could be predicted based on a measurement of female endocrine changes, the need to conduct additional macaque embryofetal development studies for type I interferons in nonhuman primates was considered unnecessary. Therefore, for the second-generation pegylated versions of the alpha interferons, only hormonal analysis was conducted in macaques. This is the only known example of where mechanistic studies have been accepted in place of developmental studies in accordance with ICH S6 guidance. 

Neuropsychiatric complications of interferon alfa were recognized in the early 1980s and represent one of the most disturbing adverse effects of interferon alfa (SED-13, 1091 SEDA-20, 327 SEDA-22, 400). Reviews have provided comprehensive analysis of the large amount of experimental and clinical data that have accumulated since 1979 (321,322). 

Several mechanisms involved in the pathogenesis of interferon alfa-induced psychiatric adverse effects have been hypothesized (Loftis 175), but the mechanisms by which interferon alfa enters the brain to produce neurotransmitter changes are unclear. In a prospective study in 48 patients who received adjuvant interferon alfa for malignant melanoma there was a positive correlation between the increase in serum concentration of soluble ICAM-1 and depression scores the authors suggested that induction of soluble ICAM-1 by interferon alfa increased the permeability of the blood-brain barrier, allowing the drug to enter the brain more readily (358). 

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