Drug Detail:Pegasys (Peginterferon alfa-2a [ peg-in-ter-feer-on-al-fa-2 a ])
Generic Name: PEGINTERFERON ALFA-2A 180ug in 1mL
Dosage Form: injection, solution
Drug Class: Antiviral interferons
Dosage Overview
Administer PEGASYS by subcutaneous injection once weekly in the abdomen or thigh for the treatment of:
- Adult patients with CHC without or with HIV coinfection [see Dosage and Administration (2.2)];
- Pediatric patients with CHC [see Dosage and Administration (2.3)] ;
- Adult patients with CHB [see Dosage and Administration (2.4)] ; and
- Pediatric patients with CHB [see Dosage and Administration (2.5)].
For treatment of CHC, use PEGASYS in combination with other HCV antiviral drugs. For information about the recommended dosage and administration and the safe and effective use of these other HCV antiviral drugs, refer to their prescribing information. PEGASYS monotherapy is only indicated in the treatment of CHC if there are contraindications to or significant intolerance to other HCV antiviral drugs.
For dosage modifications in patients with CHC or CHB:
- Due to neutropenia, thrombocytopenia, ALT elevation, and depression [see Dosage and Administration (2.6)] .
- In patients with severe renal impairment (creatinine clearance less than 30 mL/minute) and in patients with creatinine clearance between 30 and 50 mL/minute [see Dosage and Administration (2.6)] .
For important administration instructions for all the PEGASYS injection presentations (i.e., vial and prefilled syringe) [see Dosage and Administration (2.7)].
Recommended Dosage for Adults with CHC
Dosage in Adults with CHC without HIV Coinfection
Table 1 displays the recommended dosage and duration of PEGASYS and other HCV antiviral drugs in adults with CHC (without HIV coinfection) based on HCV genotype.
For treatment of HCV genotype 1 with PEGASYS in combination with ribavirin or alone, discontinuation of treatment is recommended if at least a 2 log 10 reduction from baseline in HCV RNA has not been demonstrated by 12 weeks of therapy or if undetectable HCV RNA has not been achieved after 24 weeks of therapy [see Clinical Studies (14)] . Refer to the prescribing information for specific HCV antiviral drugs used in combination with PEGASYS for information on stopping therapy based on treatment response.
Immediately discontinue PEGASYS for hepatic decompensation (Child-Pugh score greater than 6 [class B and C]).
| Hepatitis C Virus Genotype | PEGASYS Dosage | PEGASYS Duration |
|---|---|---|
|
||
| Genotypes 1, 4 † | 180 mcg subcutaneous injection in thigh or abdomen once weekly | Refer to the prescribing information of HCV antiviral drugs. |
| Genotypes 2, 3 ‡ | ||
| Genotypes 5, 6 | There are insufficient data for dosage recommendations | |
If PEGASYS monotherapy is used for treatment of CHC, the recommended PEGASYS dosage is 180 mcg via subcutaneous injection in thigh or abdomen once weekly for 48 weeks.
Dosage in Adults with CHC with HIV Coinfection
The recommended PEGASYS dosage in adults with CHC and HIV coinfection is 180 mcg subcutaneously once weekly in the thigh or abdomen. If PEGASYS is used in combination with other antiviral drugs, refer to the prescribing information of the other HCV antiviral drugs for the recommended dosage of the other HCV antiviral drugs and duration of the entire treatment regimen (including PEGASYS). If PEGASYS and ribavirin are used without other HCV antiviral drugs, the recommended duration of therapy is 48 weeks (regardless of HCV genotype).
Recommended Dosage for Pediatric Patients with CHC
PEGASYS is administered as 180 mcg/1.73 m 2 × BSA subcutaneously once weekly, to a maximum dose of 180 mcg, and should be given in combination with ribavirin. The recommended treatment duration for pediatric patients with HCV genotype 2 or 3 is 24 weeks and for other HCV genotypes is 48 weeks. Patients who initiate treatment prior to their 18 th birthday should maintain the recommended pediatric dosage (not the adult dosage) through the completion of therapy. Refer to the prescribing information of ribavirin for the recommended dosage and duration.
Recommended Dosage for Adults with CHB
The recommended PEGASYS dosage in adults with CHB is 180 mcg subcutaneously once weekly in the thigh or abdomen for 48 weeks.
Recommended Dosage for Pediatrics Patients with CHB
The recommended PEGASYS dosage in pediatric patients for HBeAg-positive CHB is 180 mcg/1.73 m 2 × BSA subcutaneously once weekly to a maximum dose of 180 mcg. The recommended duration of therapy is 48 weeks.
Maintain the recommended pediatric dosage through the entire duration of therapy in patients who turn 18 years of age during therapy.
Dosage Modifications
PEGASYS Dosage Modifications Due to Adverse Reactions, Neutropenia or Thrombocytopenia in Adults
Table 2 displays the recommended PEGASYS dosage modifications due to adverse reactions, or due to neutropenia, or thrombocytopenia in adults. Following improvement of the adverse reaction, neutropenia or thrombocytopenia, consider re-escalation of the dosage back to the previous dosage [see Warnings and Precautions (5) and Adverse Reactions (6)].
| Laboratory Values | Recommended PEGASYS Dosage |
|---|---|
| ANC = absolute neutrophil count | |
| Neutropenia | |
| ANC 500 to less than 750 cells/mm 3 | Reduce to 135 mcg subcutaneously once weekly |
| ANC less than 500 cells/mm 3 | Discontinue treatment until ANC values return to more than 1000 cells/mm 3. Reinstitute at 90 mcg subcutaneously once weekly and monitor ANC. |
| Thrombocytopenia | |
| Platelet 25,000 to less than 50,000 cells/mm 3 | Reduce to 90 mcg subcutaneously once weekly |
| Platelet less than 25,000 cells/mm 3 | Discontinue treatment |
PEGASYS Dosage Modifications Due to ALT Elevation in Adults
If ALT increases are progressive despite dose reduction or accompanied by increased bilirubin or evidence of hepatic decompensation, therapy should be immediately discontinued. In CHC patients with progressive ALT increases above baseline values, the dosage of PEGASYS should be reduced to 135 mcg and more frequent monitoring of liver function should be performed. After PEGASYS dosage reduction or withholding, therapy can be resumed after ALT flares subside.
In CHB 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 dosage of PEGASYS to 135 mcg or temporarily discontinuing treatment. After PEGASYS dosage 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.
PEGASYS Dosage Modifications Due to Depression in Adults and in Pediatric Patients
Table 3 displays the recommended PEGASYS dosage modifications in adult and pediatric patients who develop interferon-related depression or whose underlying depression worsens. Table 3 also includes recommended frequency of psychiatric visits.
| Depression Severity | Initial Depression Management (4-8 weeks) |
Depression Management After 8 Weeks | |||
|---|---|---|---|---|---|
| Dosage Modification | Visit Schedule | Depression Severity Remains Stable | Depression Severity Improves | Depression Severity Worsens | |
| Mild | No change | Evaluate once weekly by visit and/or phone | Continue weekly visit schedule | Resume normal visit schedule | Consider psychiatric consultation. Discontinue PEGASYS or reduce dosage to 135 mcg in adults (135 mcg/1.73 m 2 × BSA for pediatric patients) or 90 mcg once weekly for adults (90 mcg/1.73 m 2 × BSA for pediatric patients) |
| Moderate | Decrease PEGASYS dosage to 135 mcg in adults (135 mcg/1.73 m 2 × BSA for pediatric patients) or 90 mcg in adults (90 mcg/1.73 m 2 × BSA for pediatric patients) once weekly | 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 dosage or return to normal dosage | Obtain immediate psychiatric consultation Discontinue PEGASYS permanently. |
| Severe | Discontinue PEGASYS permanently | Obtain immediate psychiatric consultation | Psychiatric therapy necessary | ||
PEGASYS Dosage Modifications Due to Adverse Reactions or Laboratory Abnormalities in Pediatric Patients
Table 4 displays the recommended PEGASYS dosage modifications due to adverse reactions, neutropenia, thrombocytopenia, or elevated ALT in pediatric patients.
| Laboratory Abnormality | Recommended PEGASYS Dosage Modification | ||
|---|---|---|---|
| CHC | CHB | ||
| ANC = absolute neutrophil count | |||
| Neutropenia | ANC 750-999 cells/mm 3 | Week 1-2: immediate modification to 135 mcg/1.73 m 2 × BSA Week 3-48: no modification. |
No dosage modification. |
| ANC 500-749 cells/mm 3 | Week 1-2:
Week 3-48: immediate modification to 135 mcg/1.73 m 2 × BSA. |
Immediate modification to 135 mcg/1.73 m 2 × BSA. | |
| ANC 250-499 cells/mm 3 | Week 1-2: Delay or hold dosage until ANC is more than 750 cells/mm 3 then resume dose at 90 mcg/1.73 m 2 × BSA; Week 3-48: Delay or hold dosage until ANC is more than 750 cells/mm 3 then resume dosage at 135 mcg/1.73 m 2 × BSA. |
Interrupt dosing until ANC is more than or equal to 1000 cells/mm 3, then resume dose with 90 mcg/1.73 m 2 × BSA and monitor. | |
| ANC less than 250 cells/mm 3 (or febrile neutropenia): | Discontinue treatment. | Discontinue treatment. | |
| Thrombocytopenia | Platelet 25,000 to less than 50,000 cells/mm 3 | Reduce dosage to 90 mcg/1.73 m 2 × BSA. | Reduce dosage to 90 mcg/1.73 m 2 × BSA. |
| Platelet less than 25,000 cells/mm 3 | Discontinue treatment. | Discontinue treatment. | |
| Increased alanine transaminase (ALT) | For persistent or increasing elevations more than or equal to 5 but less than 10 × ULN |
|
|
| For persistent ALT values more than or equal to 10 × ULN | Discontinue treatment. | Discontinue treatment. | |
PEGASYS Dosage Modifications for Adults with Renal Impairment
Prior to administering PEGASYS, evaluate renal function. Table 5 displays the recommended dosage modifications for adults with creatinine clearance less than 30 mL/minute, including patients with end-stage renal disease requiring hemodialysis [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)]. Refer to the respective prescribing information of other HCV antiviral drugs regarding use in patients with renal impairment.
| Creatinine Clearance | Recommended PEGASYS Dosage |
|---|---|
|
|
| 30 to 50 mL/minute | 180 mcg once weekly |
| Less than 30 mL/minute including patients on hemodialysis | 135 mcg once weekly |
| Less than 30 mL/minute including patients on hemodialysis * | 135 mcg once weekly |
Preparation and Administration
Preparation and administration in adults: After proper training in subcutaneous injection, a patient may subcutaneously self-inject with PEGASYS if a healthcare provider determines that it is appropriate [see Instructions for Use] . Visually inspect PEGASYS for particulate matter and discoloration before administration (do not use if particulate matter is visible or product is discolored). Use a sterile needle and syringe to withdraw and administer PEGASYS.
Table 6 displays the recommended volume of PEGASYS to be administered for the single-dose vial and prefilled syringe presentations for the different dosages recommendations (i.e., 180, 135, or 90 mcg once weekly). Discard the unused portion of PEGASYS in single-use vials or prefilled syringes in excess of the labeled volume.
| Recommended PEGASYS Dosage | PEGASYS Dosage Forms | |
|---|---|---|
| 180 mcg/mL in a vial | 180 mcg/0.5 mL in a prefilled syringe * | |
|
||
| 180 mcg | Use entire 1 mL | Use entire 0.5 mL |
| 135 mcg | Use 0.75 mL | Use 0.375 mL |
| 90 mcg | Use 0.5 mL | Use 0.25 mL |
Preparation and administration in pediatric patients: Use the 180 mcg/ml vial to prepare pediatric dose. Use a sterile needle and syringe to withdraw and administer PEGASYS. The recommended volume of PEGASYS for pediatric dosing is based on the dosage (180 mcg/1.73 m 2 × BSA). It should be drawn from the 180 mcg/mL vial using a 1 mL tuberculin syringe.
