Pegylated interferon alfa-2a dosage and administration

Pegylated interferon alfa-2a
PEGASYS® FDA Package Insert
Description
Clinical Pharmacology
Microbiology
Indications and Usage
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
Overdosage
Dosage and Administration
How Supplied
Labels and Packages

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Dosage And Administration

PEGASYS is administered by subcutaneous injection in the abdomen or thigh. See COPEGUS prescribing information for all instructions regarding COPEGUS dosing and administration.See the Package Insert of the specific HCV NS3/4A protease inhibitor for information regarding dosing regimen, duration and administration of the protease inhibitor in combination with Pegasys and ribavirin.

Chronic Hepatitis C

Adult Patients

PEGASYS Monotherapy:

The recommended dose of PEGASYS monotherapy for chronic hepatitis C is 180 mcg (1 mL vial, 0.5 mL prefilled syringe or 0.5 mL disposable autoinjector) once weekly for 48 weeks.

PEGASYS/COPEGUS Combination Therapy:

The recommended dose of PEGASYS when used in combination with ribavirin for chronic hepatitis C is 180 mcg (1 mL vial, 0.5 mL prefilled syringe or 0.5 mL disposable autoinjector) once weekly. The recommended dose of COPEGUS and duration for PEGASYS/COPEGUS therapy is based on viral genotype (see Table 1).

The daily dose of COPEGUS is 800 mg to 1200 mg administered orally in two divided doses.

COPEGUS should be taken with food.

Pediatric Patients

PEGASYS/COPEGUS Combination Therapy:

PEGASYS is administered as 180 mcg/1.73 m2 × BSA subcutaneously once weekly, to a maximum dose of 180 mcg, and should be given in combination with COPEGUS. The recommended treatment duration for patients with genotype 2 or 3 is 24 weeks and for other genotypes is 48 weeks.

COPEGUS is available only as a 200 mg tablet and therefore the healthcare provider should determine if this sized tablet can be swallowed by the pediatric patient. COPEGUS should be administered with food. The recommended doses for COPEGUS are provided in Table 2. Patients who initiate treatment prior to their 18th birthday should maintain pediatric dosing through the completion of therapy.

Chronic Hepatitis C with HIV Coinfection

Adult Patients

PEGASYS Monotherapy:

The recommended dose of PEGASYS monotherapy for chronic hepatitis C in patients coinfected with HIV is 180 mcg (1 mL vial, 0.5 mL prefilled syringe or 0.5 mL disposable autoinjector) once weekly for 48 weeks.

PEGASYS/COPEGUS Combination Therapy:

The recommended dose when used in combination with ribavirin is PEGASYS 180 mcg once weekly and COPEGUS 800 mg orally daily given in two divided doses for a total of 48 weeks, regardless of genotype.

Since COPEGUS absorption increases when administered with a meal, patients are advised to take COPEGUS with food.

Chronic Hepatitis B

Adult Patients

PEGASYS Monotherapy:

The recommended dose of PEGASYS monotherapy for hepatitis B is 180 mcg (1 mL vial, 0.5 mL prefilled syringe or 0.5 mL disposable autoinjector) once weekly for 48 weeks.

Dose Modifications

If severe adverse reactions or laboratory abnormalities develop during combination PEGASYS/COPEGUS therapy, the dose should be modified until the adverse reactions abate. If intolerance persists after dose adjustment, PEGASYS/COPEGUS therapy should be discontinued. Table 3, Table 4, Table 5, and Table 6 provide guidelines for dose modifications and discontinuation of PEGASYS/COPEGUS based on laboratory abnormalities, patient's depression status, and cardiac status.

Adult Patients

When dose modification of PEGASYS is required for adverse reactions (clinical and/or laboratory), initial dose reduction to 135 mcg (which is 0.75 mL for the vials or adjustment to the corresponding graduation mark for the prefilled syringes) is recommended. Dose modification to 135 mcg per week can also be achieved by using a 135 mcg/0.5 mL strength disposable autoinjector. Dose reduction to 90 mcg (which is 0.5 mL for the vials or adjustment to the corresponding graduation mark for the prefilled syringes) may be needed if the adverse reaction persists or recurs. Following improvement of the adverse reaction, re-escalation of the dose may be considered [see Warnings and Precautions (5) and Adverse Reactions (6)].

Pediatric Patients

If toxicities occur which may be related to PEGASYS or COPEGUS administration, the dose of one or both drugs can be modified. Additionally, COPEGUS or PEGASYS plus COPEGUS combination therapy can be discontinued. COPEGUS should never be given as monotherapy. Recommendations for dose modifications in pediatric patients for toxicities associated with PEGASYS administration are presented in Table 5.

When dose modification is required for moderate to severe adverse reactions (clinical or laboratory), modification to 135 mcg/1.73 m2 × BSA is generally adequate. However, in some cases, dose modification to 90 mcg/1.73 m2 × BSA or 45 mcg/1.73 m2 × BSA may be needed. Up to 3 dose modifications for toxicity can be made before discontinuation is considered. These modifications apply to pediatric patients with depression, who can be managed similar to the algorithm for adult patients outlined in Table 4.

Guidelines for dose modification based on neutropenia, increased ALT levels, and decreased platelet counts for pediatric patients are provided in Table 5.

COPEGUS Dose Modifications

See COPEGUS prescribing information for all instructions regarding COPEGUS dosing and administration.

Adult and Pediatric Patients

The guidelines for COPEGUS dose modifications outlined in this table also apply to laboratory abnormalities or adverse reactions other than decreases in hemoglobin values.

Adult Patients

Once COPEGUS has been withheld due to a laboratory abnormality or clinical adverse reaction, an attempt may be made to restart COPEGUS at 600 mg daily and further increase the dose to 800 mg daily. However, it is not recommended that COPEGUS be increased to the original dose (1000 mg or 1200 mg).

Pediatric Patients

Upon resolution of a laboratory abnormality or clinical adverse reaction, an increase in COPEGUS dose to the original dose may be attempted depending upon the physician's judgment. If COPEGUS has been withheld due to a laboratory abnormality or clinical adverse reaction, an attempt may be made to restart COPEGUS at one-half the full dose.

Renal Impairment

In patients with CrCL less than 30 mL/min, including patients with end-stage renal disease requiring hemodialysis, dose reduction to 135 mcg PEGASYS is recommended. Signs and symptoms of interferon toxicity should be closely monitored. If severe adverse reactions or laboratory abnormalities develop, the dose of PEGASYS may be reduced to 90 mcg until the adverse reactions abate. If intolerance persists after dose adjustment, PEGASYS/COPEGUS therapy should be discontinued.

Renal function should be evaluated in all patients on COPEGUS. The dose of COPEGUS should be reduced for patients with creatinine clearance less than or equal to 50 mL/min [seeClinical Pharmacology (12.3) and COPEGUS prescribing information].

No data are available for pediatric subjects with renal impairment.

Liver Function

Adult Patients

If ALT increases are progressive despite dose reduction or accompanied by increased bilirubin or evidence of hepatic decompensation, therapy should be immediately discontinued.

In chronic hepatitis C patients with progressive ALT increases above baseline values, the dose of PEGASYS should be reduced to 135 mcg and more frequent monitoring of liver function should be performed. After PEGASYS dose reduction or withholding, therapy can be resumed after ALT flares subside.

In chronic hepatitis B patients with elevations in ALT (greater than 5 × ULN), more frequent monitoring of liver function should be performed and consideration should be given to either reducing the dose of PEGASYS to 135 mcg or temporarily discontinuing treatment. After PEGASYS dose reduction or withholding, therapy can be resumed after ALT flares subside.

In adult patients with persistent, severe (ALT greater than 10 times above the upper limit of normal) hepatitis B flares, consideration should be given to discontinuation of treatment.

Discontinuation of Dosing

Discontinuation of therapy should be considered if the patient has failed to demonstrate at least a 2 log10 reduction from baseline in HCV RNA titer by 12 weeks of therapy or undetectable HCV RNA after 24 weeks of therapy [see Clinical Studies (14)].

During treatment, patients' clinical status and hepatic function should be closely monitored, and PEGASYS treatment should be immediately discontinued if decompensation is observed[see Contraindications (4)].

Patients should be monitored for serious adverse reactions, some of which may become life threatening. Patients with persistently severe or worsening signs or symptoms should have their therapy withdrawn [see Boxed Warning].

See the Package Insert of the specific HCV NS3/4A protease inhibitor for information regarding discontinuation of dosing of the protease inhibitor in combination with Pegasys and ribavirin.

Preparation and Administration

A patient should self-inject PEGASYS only if the physician determines that it is appropriate and the patient agrees to medical follow-up as necessary and has been trained in proper injection technique [see illustrated FDA Approved Medication Guide for directions on injection site preparation and injection instructions].

PEGASYS should be inspected visually for particulate matter and discoloration before administration, and not used if particulate matter is visible or product is discolored. Vials, prefilled syringes, and disposable autoinjectors with particulate matter or discoloration should be returned to the pharmacist.

Discard the unused portion of PEGASYS in single-use vials or prefilled syringes in excess of the labeled volume. Use only one vial or prefilled syringe or disposable autoinjector per dose.

References

Adapted from the FDA Package Insert.