"SILVER SPRING, MD â€” The US Food and Drug Administration (FDA) is updating labeling information for the hepatitis C antivirals ledipasvir/sofosbuvir (Harvoni, Gilead Sciences) and sofosbuvir (Sovaldi, Gilead Sciences) after th"...
Chronic Hepatitis C
INFERGEN® (interferon alfacon-1) is indicated for treatment of chronic hepatitis C in patients 18 years of age or older with compensated liver disease. This indication is based on clinical trials conducted using INFERGEN as monotherapy prior to the time that combination treatment was the standard of care and on a single trial evaluating INFERGEN in combination with ribavirin in patients who failed to respond to previous treatment with a pegylated interferon and ribavirin.
The following points should be considered when initiating treatment with INFERGEN:
- Use of monotherapy with an interferon such as INFERGEN for the treatment of hepatitis C is not recommended unless a patient is unable to take ribavirin.
- The safety and efficacy of the combination of INFERGEN/ribavirin in treatment-naïve patients or in patients co-infected with HBV or HIV-1 have not been evaluated.
- Patients with the following characteristics are less likely to benefit from retreatment with combination therapy: response of < 1 log10 drop HCV RNA on previous treatment, Genotype 1, high viral load ( ≥ 850,000 IU/mL), African American race, and/or presence of cirrhosis.
- No safety and efficacy data are available for treatment of longer than one year.
DOSAGE AND ADMINISTRATION
INFERGEN Monotherapy Dosing
The recommended dose of INFERGEN monotherapy for the initial treatment of chronic HCV infection is 9 mcg administered three times a week as a single subcutaneous injection for 24 weeks [see Clinical Studies, Medication Guide for instructions].
The recommended dose of INFERGEN monotherapy for patients who tolerated previous interferon therapy and did not respond or relapsed following its discontinuation is 15 mcg administered three times a week as a single subcutaneous injection for up to 48 weeks [see Clinical Studies, Medication Guide for instructions]. Patients who do not tolerate initial standard interferon therapy should not be treated with INFERGEN therapy 15 mcg three times a week.
Combination Treatment with INFERGEN/Ribavirin Dosing
The recommended dose of INFERGEN is 15 mcg daily administered as a single subcutaneous injection in combination with weight-based ribavirin at 1,000 mg -1,200 mg ( < 75 kg and ≥ 75 kg) orally in two divided doses for up to 48 weeks. [see Clinical Studies, Medication Guide for instructions].
Ribavirin should be taken with food. INFERGEN/ribavirin should not be used in patients with creatinine clearance < 50 mL/min [see CONTRAINDICATIONS].
If a serious adverse reaction develops during the course of treatment [see WARNINGS AND PRECAUTIONS] discontinue or modify the dosage of INFERGEN and/or ribavirin until the adverse event abates or decreases in severity. If persistent or recurrent serious adverse events develop despite adequate dosage adjustment, discontinue treatment. Upon resolution or improvement of the adverse reaction, resuming INFERGEN and/or ribavirin may be considered.
INFERGEN Monotherapy Dose Modifications
Dose reduction to 7.5 mcg may be necessary following a serious adverse reaction. If serious adverse events continue to occur, dosing should be interrupted or discontinued as the efficacy of lower doses has not been established.
INFERGEN/Ribavirin Combination Therapy Dose Modifications
Stepwise dose reduction from 15 mcg to 9 mcg and from 9 mcg to 6 mcg may be necessary for serious adverse reactions.
Guidelines for INFERGEN/Ribavirin Dose Modifications
Tables 1, 2, and 3 provide guidelines for dose modifications and discontinuation of INFERGEN and/or ribavirin based on depression or laboratory parameters.
Table 1: Guidelines for Dose Modification or
Discontinuation of INFERGEN and for Scheduling Visits for Patients with
|Depression Severity*||Initial Management (4–8 Weeks)||Depression|
|Dose Modification||Visit Schedule||Remains Stable||Improves||Worsens|
|Mild||No change to INFERGEN dose or ribavirin dose.||Evaluate once weekly by visit and/or phone.||Continue weekly visit schedule.||Resume normal visit schedule.||(See moderate or severe depression)|
|Moderate||Decrease INFERGEN dose from 15 mcg to 9 mcg; or from 9 mcg to 6 mcg, no change to ribavirin dose.||Evaluate once weekly (office visit at least every other week).||Consider psychiatric consultation. Continue reduced dosing.||If symptoms improve and are stable for 4 weeks, may resume normal visit schedule. Continue reduced INFERGEN dosing or return to normal INFERGEN dose.||(See severe depression)|
|Severe||Discontinue INFERGEN and ribavirin permanently.||Not applicable.||Psychiatric therapy necessary.||Not applicable.||Not applicable.|
|*See DSM-IV for definitions.|
Table 2: Guidelines for Dose
Modification or Discontinuation of INFERGEN for Hematologic Toxicities
|ANC < 0.75 × 109/L||Reduce INFERGEN dose from 15 mcg to 9 mcg, or from 9 mcg to 6 mcg; maintain ribavirin dose at 1200 mg or 1000 mg.|
|ANC < 0.50 × 109/L||INFERGEN and ribavirin treatment should be suspended until ANC values return to more than 1000/mm³ .|
|Platelet Count < 50 × 109/L||Reduce INFERGEN dose from 15 mcg to 9 mcg or from 9 mcg to 6 mcg; maintain ribavirin dose at 1200 mg or 1000 mg.|
|Platelet Count < 25 × 109/L||INFERGEN and ribavirin treatment should be discontinued.|
Table 3: Guidelines for Dose Modification or
Discontinuation of INFERGEN/Ribavirin for the Management of Anemia*
|Hgb < 10 g/dL||History of Cardiac or Cerebrovascular Disease, reduce dose of INFERGEN||Adjust dose**|
|Hgb < 8.5 g/dL||Permanently discontinue||Permanently discontinue|
|* For adult patients with a history of stable cardiac
disease receiving INFERGEN in combination with ribavirin, the INFERGEN dose
should be reduced from 15 mcg to 9 mcg or 9 mcg to 6 mcg and the ribavirin dose
by 200 mg/day if a > 2 g/dL decrease in hemoglobin is observed during any
4-week period. Both INFERGEN and ribavirin should be permanently discontinued
if patients have hemoglobin levels < 12 g/dL after this ribavirin dose
** 1st dose reduction of ribavirin is by 200 mg/day. 2nd dose reduction of ribavirin (if needed) is by an additional 200 mg/day.
Discontinuation of Treatment
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 [See Clinical Studies].
Ribavirin should be discontinued in any patient who temporarily or permanently discontinues INFERGEN.
Preparation and Administration
Just prior to injection, INFERGEN may be allowed to reach room temperature.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration; if particulates or discoloration are observed, the vial should not be used.
If home use is determined to be desirable by the physician, instructions on appropriate use should be given by a healthcare professional. After administration of INFERGEN, it is essential to follow the procedure for proper disposal of syringes and needles. [see Medication Guide for detailed instructions].
Dosage Forms And Strengths
INFERGEN is provided in single-use vials containing:
- 9 mcg/0.3 mL INFERGEN in sterile, clear, colorless, preservative-free liquid
- 15 mcg/0.5 mL INFERGEN in sterile, clear, colorless, preservative-free liquid
Storage And Handling
Use only one vial per dose; do not re-enter the vial. Discard unused portions. Do not save unused drug for later administration.
Single-use, preservative-free vials containing 9 mcg (0.3 mL) of interferon alfacon-1 are available in dispensing packs of 6 vials (NDC 66435-202-09).
Single-use, preservative-free vials containing 15 mcg (0.5 mL) of interferon alfacon-1 are available in dispensing packs of 6 vials (NDC 66435-201-15).
INFERGEN should be stored in the refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze. Avoid vigorous shaking and exposure to direct sunlight.
Manufactured by: Boehringer Ingelheim Pharma GmbH & Co. Biberach, Germany. Manufactured for: Kadmon Pharmaceuticals, LLC Warrendale, PA 15086, USA (877) 377-7862. Revised: May 2013
Last reviewed on RxList: 6/17/2013
This monograph has been modified to include the generic and brand name in many instances.
Additional Infergen Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.