Interferon Alfacon-1 Dosage

Usual Adult Dose for Chronic Hepatitis C

Monotherapy:
For initial treatment: 9 mcg subcutaneously 3 times a week for 24 weeks

For patients who tolerated previous interferon therapy and did not respond or relapsed after its discontinuation: 15 mcg subcutaneously 3 times a week for up to 48 weeks

Patients who did not tolerate initial standard interferon therapy should not be treated with interferon alfacon-1 15 mcg 3 times a week.

Combination therapy:
Less than 75 kg: Interferon alfacon-1 15 mcg subcutaneously once a day plus ribavirin 1000 mg/day orally in 2 divided doses for up to 48 weeks

75 kg or more: Interferon alfacon-1 15 mcg subcutaneously once a day plus ribavirin 1200 mg/day orally in 2 divided doses for up to 48 weeks

Renal Dose Adjustments

The manufacturer recommends closely monitoring patients with impaired renal function for signs and symptoms of interferon toxicity and adjusting the interferon alfacon-1 dose as recommended for patients with depression, for hematologic toxicities, and for the management of anemia.

CrCl less than 50 mL/min: Ribavirin is contraindicated; therefore, combination therapy with interferon alfacon-1 plus ribavirin should not be used.

Liver Dose Adjustments

Hepatic decompensation (Child-Pugh score greater than 6 [class B and C]): Contraindicated

Dose Adjustments

If a severe adverse reaction develops during treatment, the dosage of interferon alfacon-1 and/or ribavirin should be discontinued or modified until the adverse event abates or decreases in severity. If persistent or recurrent serious adverse events develop despite adequate dosage adjustment, therapy should be discontinued. Upon resolution or improvement of the adverse reaction, resuming interferon alfacon-1 and/or ribavirin may be considered.

Monotherapy: Dose reduction to 7.5 mcg may be necessary following a serious adverse event. If serious adverse events continue to occur, dosing should be interrupted or discontinued as the efficacy of lower doses has not been established.

Combination therapy: Stepwise dose reduction from 15 mcg to 9 mcg and from 9 mcg to 6 mcg may be needed for serious adverse reactions.

Based on depression (DSM-IV):
Mild: No adjustment recommended.

Moderate:
Interferon alfacon-1: Dose should be reduced from 15 mcg to 9 mcg or from 9 mcg to 6 mcg. Patient should be evaluated once weekly (office visit at least every other week). If symptoms improve and are stable for 4 weeks, recommendations are to continue reduced dosing or return to normal dose.

Ribavirin: No adjustment recommended.

Severe: Interferon alfacon-1 and ribavirin should be permanently discontinued. Psychiatric therapy may be necessary.

Based on laboratory values:
Absolute neutrophil count (ANC) less than 0.75 x 10(9)/L:
Interferon alfacon-1: Dose should be reduced from 15 mcg to 9 mcg or from 9 mcg to 6 mcg.
Ribavirin: No adjustment recommended.

ANC less than 0.5 x 10(9)/L: Interferon alfacon-1 and ribavirin should be suspended until ANC values return to more than 1000/mm3.

Platelet count less than 50 x 10(9)/L:
Interferon alfacon-1: Dose should be reduced from 15 mcg to 9 mcg or from 9 mcg to 6 mcg.
Ribavirin: No adjustment recommended.

Platelet count less than 25 x 10(9)/L: Interferon alfacon-1 and ribavirin should be discontinued.

Management of anemia:
Hemoglobin (Hgb) less than 10 g/dL:
Interferon alfacon-1: Dose should be reduced from 15 mcg to 9 mcg or from 9 mcg to 6 mcg in patients with history of cardiac or cerebrovascular disease.

Ribavirin:
First dose reduction: Dose should be reduced by 200 mg/day.
Second dose reduction (if needed): Dose should be reduced by an additional 200 mg/day.

Hgb less than 8.5 g/dL: Interferon alfacon-1 and ribavirin should be permanently discontinued.

Management of anemia in patients with history of stable cardiac disease:
Greater than 2 g/dL decrease in Hgb during any 4-week period:
Interferon alfacon-1: Dose should be reduced from 15 mcg to 9 mcg or from 9 mcg to 6 mcg.
Ribavirin: Dose should be reduced by 200 mg/day.

Hgb less than 12 g/dL following reduction of ribavirin dose: Interferon alfacon-1 and ribavirin should be permanently discontinued.

Patients who fail to achieve at least a 2 log10 drop at 12 weeks or undetectable HCV-RNA at week 24 are highly unlikely to achieve SVR and discontinuation of therapy should be considered.

Ribavirin should be discontinued in any patient who temporarily or permanently discontinues interferon alfacon-1.

Precautions

Alpha interferons, including interferon alfacon-1, cause or aggravate fatal or life-threatening neuropsychiatric, ischemic, autoimmune, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Patients with persistently severe or worsening symptoms of these conditions should be withdrawn from treatment. In many but not all cases, these disorders resolve after stopping interferon alfacon-1 treatment.

Interferon alfacon-1 is contraindicated in patients with hepatic decompensation (Child-Pugh score greater than 6 [class B and C]) and autoimmune hepatitis.

Chronic hepatitis C patients with cirrhosis may be at risk of hepatic decompensation when administered alpha interferons, including interferon alfacon-1. During therapy, patients' clinical status and hepatic function should be closely monitored, and interferon alfacon-1 therapy should be discontinued at once if symptoms of hepatic decompensation (such as jaundice, ascites, coagulopathy, or decreased serum albumin) are observed.

Interferon alfacon-1 plus ribavirin combination therapy is contraindicated in patients with hemoglobinopathies (e.g., sickle cell anemia, thalassemia major), in pregnant women, and in men whose female partners are pregnant.

The manufacturer recommends that patients undergo pregnancy tests prior to the start of therapy, then monthly during treatment, and for 6 months following treatment cessation. If pregnancy occurs in a patient or partner of a patient during treatment with interferon alfacon-1 and ribavirin or during the 6 months after treatment, physicians should report such cases by calling the Ribavirin Pregnancy Registry at 1-800-593-2214 (USA).

Treatment with interferon alfacon-1, alone or in combination with ribavirin, should be given under the guidance of a qualified prescriber, and may lead to moderate-to-severe adverse experiences requiring dosage reduction, temporary dose cessation, or discontinuation of further therapy.

Ribavirin caused hemolytic anemia in 30% of patients treated with interferon alfacon-1 plus ribavirin. Complete blood counts should be obtained before starting treatment, and at 2 and 4 weeks, or more often if necessary. Decrease in dosage or discontinuation of ribavirin may be required.

Severe psychiatric adverse events (including depression, suicidal ideation, suicide attempt, suicide, and homicidal ideation) may manifest in patients receiving interferon alpha therapy, including interferon alfacon-1. Other prominent psychiatric adverse events may occur, including psychosis, aggressive behavior, anxiety, nervousness, emotional lability, abnormal thinking, agitation, apathy, and relapse of drug addiction. Interferon alfacon-1 therapy should be used with extreme caution in patients who report a history of depression. Prescribers should monitor all patients for evidence of depression and other psychiatric symptoms. Prior to initiation of interferon alfacon-1 treatment, patients should be informed about potential development of depression and should be advised to immediately report any sign or symptom of depression and/or suicidal ideation. Patients developing psychiatric problems, including clinical depression, should be carefully monitored during therapy and in the 6-month follow-up period. If psychiatric symptoms persist or worsen, or suicidal ideation or aggressive behavior towards others is observed, interferon alfacon-1 should be discontinued and the patient should be followed, with psychiatric intervention as appropriate. In severe cases, treatment should be stopped immediately and psychiatric intervention instituted.

Alpha interferons suppress bone marrow function and may result in severe cytopenias including aplastic anemia. It is recommended that complete blood counts be obtained pretreatment and monitored routinely during therapy. Interferon alfacon-1 should be discontinued in patients who develop severe decreases in neutrophils or platelet counts. Ribavirin may worsen neutropenia caused by interferon alfacon-1. Interferon alfacon-1 plus ribavirin combination therapy should be used with caution in patients with low baseline neutrophil counts (less than 1500 cells/mm3) and may require discontinuation if a severe decrease in neutrophil count occurs.

Interferon alfacon-1 should be given with caution to patients with abnormally low peripheral blood cell counts and patients taking myelosuppressive agents. Transplantation patients or other chronically immunosuppressed patients should be treated with interferon alpha therapy with caution.

Neutropenia, thrombocytopenia, hypertriglyceridemia, and thyroid disorders have been reported with interferon alfacon-1. These laboratory parameters should be monitored closely.

Cardiovascular events including hypotension, arrhythmia, tachycardia, cardiomyopathy, angina pectoris, and myocardial infarction have been reported in patients treated with interferon alfacon-1. Interferon alfacon-1 should be administered with caution to patients with cardiovascular disease. Close monitoring is recommended if interferon alfacon-1 is required in patients with a history of myocardial infarction and arrhythmic disorder. Interferon alfacon-1 plus ribavirin combination therapy should not be used in patients with a history of significant or unstable cardiac disease. Patients with preexisting cardiac abnormalities should have electrocardiograms administered before initiating treatment with interferon alfacon-1 and ribavirin.

Serious hypersensitivity reactions have been reported following treatment with alfa interferons. If hypersensitivity reactions occur, interferon alfacon-1 should be discontinued immediately and appropriate medical treatment instituted.

Caution is advised when initiating therapy in patients with a history of endocrine disorders. Occurrence or aggravation of hyperthyroidism or hypothyroidism has been reported with interferon alfacon-1 therapy. Hyperglycemia and diabetes mellitus have also been reported in patients treated with interferon alfacon-1. Patients who develop these conditions during therapy that cannot be controlled with medication should not continue interferon alfacon-1 therapy.

Development or exacerbation of autoimmune disorders has been observed in patients receiving alpha interferon therapies, including interferon alfacon-1. Interferon alfacon-1 should not be used in patients with autoimmune hepatitis and should be used with caution in patients with other autoimmune disorders.

Dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension, and sarcoidosis (sometimes fatal or resulting in respiratory failure) may be induced or aggravated by alpha interferon treatment, including interferon alfacon-1. Patients who develop persistent or unexplained pulmonary infiltrates or pulmonary function impairment should discontinue therapy with interferon alfacon-1. Respiratory failure has recurred with interferon rechallenge. Interferon alfacon-1 should be suspended in patients who develop pulmonary infiltrates or pulmonary function impairment. Patients who restart interferon therapy should be monitored closely.

Hemorrhagic/ischemic colitis, sometimes fatal, has been reported within 12 weeks of alpha interferon therapies and has been reported in patients treated with interferon alfacon-1. Interferon alfacon-1 therapy should be discontinued immediately in patients who develop signs and symptoms of colitis.

Pancreatitis, sometimes fatal, has been reported in patients treated with alpha interferons, including interferon alfacon-1. Interferon alfacon-1 therapy should be suspended in patients with signs and symptoms suggestive of pancreatitis and discontinued in patients diagnosed with pancreatitis.

Decrease or loss of vision, retinopathy (including macular edema, retinal artery or vein thrombosis, retinal hemorrhage, cotton wool spots), optic neuritis, papilledema, and serous retinal detachment are induced or aggravated by treatment with interferon alfacon-1 or other alpha interferons. Before the start of therapy, all patients should receive an eye examination. Patients with preexisting eye disorders (e.g., diabetic or hypertensive retinopathy) should receive periodic ophthalmologic exams during interferon alpha therapy. Any patient who develops ocular symptoms should be given a prompt and complete eye examination. Interferon alfacon-1 treatment should be discontinued in any patient who develops new or worsening ophthalmologic disorders.

Increases in serum creatinine levels (including renal failure) have been reported in patients receiving interferon alfacon-1. Interferon alfacon-1 therapy has not been studied in patients with renal insufficiency. Renal function should be evaluated in all patients starting interferon alfacon-1 alone or with ribavirin therapy. Patients with impaired renal function should be closely monitored for signs and symptoms of interferon toxicity, including increases in serum creatinine.

Laboratory tests are recommended for all patients on interferon alfacon-1 therapy, prior to beginning treatment (baseline), 2 weeks after initiation of treatment, and periodically thereafter during the 24 or 48 weeks of therapy at the discretion of the physician. Patients should be well hydrated, especially during the initial stages of therapy. Following completion of interferon alfacon-1 treatment, any abnormal test values should be monitored periodically.

The entrance criteria used for the clinical study of interferon alfacon-1 may be considered a guideline to acceptable baseline values for the initiation of treatment. These entrance criteria included:

• Platelet count greater than or equal to 75 x 10(9)/L
• Hemoglobin concentration greater than or equal to 10 g/dL
• Absolute neutrophil count greater than or equal to 1500 x 10(6)/L
• Serum creatinine concentration less than 2 mg/dL or CrCl greater than 50 mL/min
• Serum albumin concentration greater than or equal to 25 g/L
• Bilirubin less than or equal to 1.4 mg/dL (with the exception of patients with Gilbert's syndrome)
• Thyroid stimulating hormone and thyroxine within normal limits

The safety and efficacy of treatment beyond 1 year have not been established. The safety and efficacy of interferon alfacon-1, alone or in combination with ribavirin, for the treatment of chronic hepatitis C virus infection have not been established in liver or other organ transplant recipients, in patients coinfected with HIV or hepatitis B virus, or in patients with hepatic and/or renal impairment. The safety and efficacy of interferon alfacon-1 in combination with ribavirin have not been established in treatment-naive patients.

Safety and efficacy have not been established in pediatric patients (less than 18 years of age).

Dialysis

Data not available

Other Comments

Use of monotherapy with an interferon (such as interferon alfacon-1) for the treatment of hepatitis C is not recommended unless a patient is unable to take ribavirin.

Patients with response of less than 1 log10 drop HCV RNA on previous treatment, high viral load (greater than or equal to 850,000 international units/mL), African American race, presence of cirrhosis, and/or genotype 1 infection are less likely to benefit from retreatment with combination therapy.

Further information

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