Interferon therapy adverse effects

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. 

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

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

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. 

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. 

The FDA has expanded the indications for a combination product to include patients with chronic hepatitis C who have not been treated with interferon alfa. This product, Rebetron Combination Therapy (Schering), contains recombinant interferon alfa-2b for injection (Intron A) plus ribavirin (Rebetol) in capsules, and was previously only approved for patients who had relapsed after treatment with interferon alone (401). Serious adverse effects, such as depression, suicidal ideation, and suicide, have occurred with this regimen and patients should be closely monitored. 

Adverse effects include a flu-like syndrome at the start of therapy that decreases in severity as treatment progresses. Interferon beta-1 a is a potential abortifacient and an inhibitor of cytochrome P-450. 

Because a-interferon therapy can exacerbate autoimmune disorders, it is important to exclude autoimmune diagnoses before initiating therapy. Thrombocytopenia and granulocytopenia are more common in patients with cirrhosis and hypersplenism. The psychiatric complications are especially severe in those with severe liver disease, occur in up to 20% of patients, and are the most common dose-limiting side effects. Therapy should be discontinued if serious complications occur. The dose of a-interferon must be reduced in 10% to 40% of patients. Treatment must be discontinued because of adverse effects in 5% to 10% of patients. For many patients, reassurance that the side effects are therapy related, not severe, and will disappear when therapy is stopped is sufficient. It is always important to reassure both patient and family, especially when psychiatric side effects are evident. These points are critical given that patient adherence is crucial to the ultimate success of HCV treatment. ... 

Intriguingly, in vitro data suggest a potential synergism between glatiramer acetate and interferon-/ . Given the cost of these therapies, as well as the potential for additive adverse effects, this therapeutic combination cannot be recommended until clinical evidence demonstrating benefit is available. A study that will compare glatiramer acetate alone with interferon-/ - a (Avonex) alone versus a combination of the two has just been funded by NIH and is underway, with results expected in several years. 

Because of the associated toxicity and adverse effects seen with interferon-a therapy there has been worldwide concern about the usefulness of this intensive adjuvant therapy for melanoma despite the possible benefits in relapse-free and overall survival. A subsequent report from the cooperative group study demonstrated a quality-of-life benefit with interferon therapy based on the quality-of-life-adjusted survival analysis. This analysis calculates the quality-of-life-adjusted years gained as a result of interferon-a treatment or the clinical benefit of time without toxicities and without disease. 

Interferon-o, a 165 amino acid glycoprotein, is effective in the treatment of viral hepatitis C and B, myeloma, melanoma, and renal carcinoma. Little is known about the renal metabolism of interferon-a despite extensive studies in experimental animals. In patients with normal renal function, the serum peak level occurs 8 hours after a subcutaneous injection of 3x10 units of interferon-a. Terminal elimination half-life ranges from 4 to 16 hours and after 24 to 48 hours, the interferon molecule is undetectable in the serum [181]. A-interferon urinary level is undetectable. Some authors have suggested that, despite the lack of urinary excretion, the kidney could play a role in interferon-a metabolism [182]. Indeed, as far as hepatitis C treatment is concerned, dialysis patients often show a better response to therapy than non-dialysis patients. This better efficacy in dialysis patients is associated with an increase of the incidence of adverse effects. This observation raises the question of pharmacokinetic modifications. One study documented that clearance kinetics of interferon-a in patients with chronic renal failure are about half the rate of patients with normal renal function [183]. Indeed interferon is filtered by the glomeruli and largely absorbed and catabolized within tubular cells [184]. 

INTERFERON GAMMA VACCINES Immunosuppressants diminish the effectiveness of vaccines. There is t risk of adverse/toxic effects of live vaccines, and vaccinal infections may develop Disseminated infection due to enhanced replication of vaccine virus in the presence of diminished immunocompetence Do not vaccinate when patients are on immunosuppressants. Vaccination should be deferred for at least 3 months after discontinuing suppressants/myelosuppres-sants. If an individual has been recently vaccinated, do not initiate therapy for at least 2 weeks after vaccination... 

Ten to thirty percent of patients progress to cirrhosis after 30 years. Most individuals with chronic HCV in the United States are between the ages of 30 and 49 years and have yet to manifest sequelae of the disease. As a result, the impact of HCV on future health care costs is anticipated to be high. Unfortunately, clinical decisions to treat individual patients are confounded by the inconsistent progression and a lack of ability to predict clinical deterioration. Therapy with pegylated interferons and ribavirin can be very expensive and associated with serious adverse events. Consequently, assessing the cost, benefits, and cost-effectiveness of the various therapies is vital. 

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