"The European Medicines Agency (EMA) has launched a review of the six direct-acting antivirals approved for use in the European Union for treating chronic hepatitis C virus infection, the agency said today.
They are daclatasvir (Dak"...
Chronic Hepatitis C
PEGASYS, as part of a combination regimen with other hepatitis C virus (HCV) antiviral drugs, is indicated for the treatment of adults with chronic hepatitis C (CHC) with compensated liver disease. For information about the safe and effective use of other HCV antiviral drugs to be used in combination with PEGASYS, refer to their prescribing information. PEGASYS in combination with ribavirin is indicated for treatment of pediatric patients 5 years of age and older with CHC and compensated liver disease. PEGASYS monotherapy is only indicated for the treatment of patients with CHC with compensated liver disease if there are contraindications or significant intolerance to other HCV antiviral drugs.
Limitations of Use
- PEGASYS alone or in combination with ribavirin without additional HCV antiviral drugs is not recommended for treatment of patients with CHC who previously failed therapy with an interferon-alfa.
- PEGASYS is not recommended for treatment of patients with CHC who have had solid organ transplantation [see Use in Specific Populations].
Chronic Hepatitis B (CHB)
PEGASYS is indicated for the treatment of adult patients with HBeAg-positive and HBeAg-negative chronic hepatitis B infection who have compensated liver disease and evidence of viral replication and liver inflammation.
DOSAGE AND ADMINISTRATION
Administer PEGASYS by subcutaneous injection once weekly in the abdomen or thigh for the treatment of:
- Adult patients with chronic hepatitis C (CHC) without or with HIV coinfection [see Adult Patients with CHC 2.4 Chronic Hepatitis B]; and
- Pediatric patients with CHC [see Pediatric Patients with CHC]; and
- Adult patients with chronic hepatitis B (CHB) [see Chronic Hepatitis B].
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 Modifications].
- 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 Modifications].
For important administration instructions for all the PEGASYS injection presentations (i.e., vial, prefilled syringe, autoinjector) see Preparation and Administration.
Adult Patients With Chronic Hepatitis C
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 log10 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]. 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]).
Table 1 : Recommended Adult Dosage for PEGASYS for CHC
|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 is insufficient data for dosage recommendations|
|1If PEGASYS is used in combination with other
antiviral drugs for CHC, 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.
* If PEGASYS and ribavirin are used without other HCV antiviral drugs the recommended duration of therapy is 48 weeks.
** If PEGASYS and ribavirin are used without other HCV antiviral drugs the recommended duration of therapy is 24 weeks.
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).
Pediatric Patients With CHC
PEGASYS is administered as 180 mcg/1.73 m² x 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 18th 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.
Adults With Chronic Hepatitis B (CHB)
The recommended PEGASYS dosage in adults with CHB is 180 mcg subcutaneously once weekly in the thigh or abdomen for 48 weeks.
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 and ADVERSE REACTIONS].
Table 2 : Recommended PEGASYS Dosage Modifications Due
to Adverse Reactions, Neutropenia or Thrombocytopenia in Adults
|Laboratory Values||Recommended PEGASYS Dosage|
|ANC < 750 cells/mm³||Reduce to 135 mcg subcutaneously once weekly|
|ANC < 500 cells/mm³||Discontinue treatment until ANC values return to more than 1000 cells/mm³. Reinstitute at 90 mcg subcutaneously once weekly and monitor ANC.|
|Platelet < 50,000 cells/mm³||Reduce to 90 mcg subcutaneously once weekly|
|Platelet < 25,000 cells/mm³||Discontinue treatment|
|ANC = absolute neutrophil count|
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 chronic hepatitis B patients with elevations in ALT (greater than 5 x 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.
Dosage Modifications Due to Depression
Table 3 displays the recommended PEGASYS dosage modifications in adults and pediatric patients who develop interferon-related depression or whose underlying depression worsens. Table 3 also includes recommended frequency of psychiatric visits.
Table 3 : Recommended PEGASYS Dosage Modifications and
Psychiatric Visits Due to Depression in Adult & Pediatric Patients
|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 (135 mcg/1.73 m² x BSA for pediatric patients) or 90 mcg once weekly (90 mcg/1.73 m² x BSA for pediatric patients)|
|Moderate||Decrease PEGASYS dosage to 135 mcg (135 mcg/1.73 m² x BSA for pediatric patients) or 90 mcg (90 mcg/1.73 m² x 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|
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 liver enzymes in pediatric patients with CHC.
Table 4 : Recommended PEGASYS Dosage Modifications for
Neutropenia, Thrombocytopenia, and Elevated ALT in Pediatric Patients
|Laboratory Abnormality||Recommended PEGASYS Dosage Modification|
|Neutropenia||ANC 750-999 cells/mm³||Week 1-2: immediate modification to 135 mcg/1.73 m² x BSA
Week 3-48: no modification.
|ANC 500-749 cells/mm³||Week 1-2:
|ANC 250-499 cells/mm³||Week 1-2: Delay or hold dosage until > 750 cells/mm³ then resume dose at 90 mcg/1.73 m² x BSA;
Week 3-48: Delay or hold dosage until > 750 cells/mm³ then resume dosage at 135 mcg/1.73 m² x BSA.
|ANC < 250 cells/mm³ (or febrile neutropenia):||Discontinue treatment.|
|Thrombocytopenia||Platelet < 50,000 cells/mm³||Reduce dosage to 90 mcg/1.73 m² x BSA.|
|Increased alanine transaminase (ALT)||For persistent or increasing elevations ≥5 but < 10 x ULN,||
|For persistent ALT values ≥10 x ULN||Discontinue treatment.|
Dosage Modifications in Adults and Pediatric Patients with Renal Impairment
Prior to administering PEGASYS, evaluate renal function. Table 5 displays the recommended dosage modifications in adults with creatinine clearance less than 30 mL/minute, including patients with end-stage renal disease requiring hemodialysis [see Use In Specific Populations and CLINICAL PHARMACOLOGY]. Because there are no data in pediatric patients with renal impairment, dosage recommendations in pediatric patients are not provided. Refer to the respective prescribing information of other HCV antiviral drugs regarding use in patients with renal impairment.
Table 5 : PEGASYS Dosage
Modification for Adults 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|
|* If severe adverse reactions or laboratory abnormalities develop, PEGASYS dose can be reduced to 90 mcg once weekly until adverse reactions abate. If intolerance persists after dosage adjustment, PEGASYS should be discontinued.|
Preparation And Administration
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).
Table 6 displays the recommended volume of PEGASYS to be administered for the single-dose vial, prefilled syringe, and autoinjector 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.
Table 6 : Use of the Vial, Prefilled Syringe, and
Autoinjector for Different PEGASYS Dosages
|Recommended PEGASYS Dosage||PEGASYS Presentations|
|180 mcg/mL in a vial||180 mcg/0.5 mL in a prefilled syringe||180 mcg/0.5 mL in an autoinjector||135 mcg/0.5 mL in an autoinjector|
|180 mcg||Use entire 1 mL||Use entire 0.5 mL||May use||Do not use|
|135 mcg||Use 0.75 mL||Use 0.375 mL||Do not use||May use|
|90 mcg||Use 0.5 mL||Use 0.25 mL||Do not use||Do not use|
Dosage Forms And Strengths
Injection (all presentations below are single-dose):
- 180 mcg/mL in a vial
- 180 mcg/0.5 mL in a prefilled syringe
- 180 mcg/0.5 mL in an autoinjector
- 135 mcg/0.5 mL in an autoinjector
|Each PEGASYS Single Use Vial Package Contains:|
|A box containing 180 mcg per 1 mL solution in a single use vial.||(NDC 0004-0350-09)|
|Each PEGASYS Prefilled Syringe Monthly Convenience Pack Contains:|
|A box containing four 180 mcg per 0.5 mL (½ cc) single use prefilled syringes with 4 needles with or without 4 alcohol swabs. Each prefilled syringe is supplied with a 27-gauge, ½-inch needle with a needle-stick protection device.||(NDC 0004-0352-39) with alcohol swabs (NDC 0004-0357-30) without alcohol swabs|
|Each PEGASYS ProClick™ Autoinjector Package Contains:|
|A box containing one 180 mcg per 0.5 mL PEGASYS ProClick™single use autoinjector.||(NDC 0004-0365-09)|
|A box containing one 135 mcg per 0.5 mL PEGASYS ProClick™single use autoinjector.||(NDC 0004-0360-09)|
|Each PEGASYS ProClick™ Autoinjector Monthly Convenience Pack Contains:|
|A box containing four 180 mcg per 0.5 mL PEGASYS ProClick™single use autoinjectors.||(NDC 0004-0365-30)|
|A box containing four 135 mcg per 0.5 mL PEGASYS ProClick™single use autoinjectors.||(NDC 0004-0360-30)|
Storage And Handling
Store in the refrigerator at 2°C to 8°C (36°F to 46°F). Do not leave PEGASYS out of the refrigerator for more than 24 hours. Do not freeze or shake. Protect from light. Vials, prefilled syringes and autoinjectors are for single use only. Discard any unused portion remaining in the vial, prefilled syringe.
If home use is prescribed, a puncture-resistant container for the disposal of used needles, syringes and autoinjectors should be supplied to the patients. Patients should be thoroughly instructed in the importance of proper disposal and cautioned against any reuse of any needles, syringes and autoinjectors. The full container should be disposed of according to the directions provided by the physician [see FDA-Approved Medication Guide].
Manufactured by: Hoffmann-La Roche, Inc. c/o Genentech, Inc. Distributed by: Genentech USA, Inc. A Member of the Roche Group 1 DNA Way South San Francisco, CA 94080-4990This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 3/30/2015
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