Peginterferon Alfa 2a

Your pharmacist can provide more information about peginterferon alfa-2a.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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Peginterferon alfa-2a may be found in some form under the following brand names:

• Pegasys

Peginterferon alfa-2a is part of the drug class:

• interferon

• Store peginterferon alfa-2a single use vials and prefilled syringes in a refrigerator, at 36°F to 46°F (2°C to 8°C).
• Do not freeze or shake peginterferon alfa-2a.
• Protect peginterferon alfa-2a from light. Keep peginterferon alfa-2a vials, prefilled syringes, and all medicines out of the reach of children.

WARNING:

Alpha interferons, including peginterferon alfa-2a, may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping peginterferon alfa-2a therapy.

Use with Ribavirin

Ribavirin, including Copegus, may cause birth defects and/or death of the fetus. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin causes hemolytic anemia. The anemia associated with ribavirin therapy may result in a worsening of cardiac disease.

Usual Adult Dose for Chronic Hepatitis C:

PATIENTS WITHOUT HIV COINFECTION:
Combination Therapy:
-HCV genotypes 1, 2, 3, 4: 180 mcg subcutaneously once a week
-HCV genotypes 5, 6: Insufficient data for dosing recommendations

Duration of therapy when used with other HCV antiviral drugs:
-HCV genotypes 1, 2, 3, 4: The manufacturer product information of the other HCV antiviral drugs should be consulted.

Duration of therapy when used with ribavirin without other HCV antiviral drugs:
-HCV genotypes 1, 4: 48 weeks
-HCV genotypes 2, 3: 24 weeks

Monotherapy: 180 mcg subcutaneously once a week for 48 weeks

Discontinuation of Therapy for HCV Genotype 1 (when used with ribavirin or alone):
-Therapy should be discontinued if there is not at least a 2 log10 reduction from baseline in HCV RNA by 12 weeks of therapy or if HCV RNA remains detectable after 24 weeks of therapy.
-The manufacturer product information for specific coadministered HCV antiviral drugs should be consulted for information on discontinuation based on treatment response.

PATIENTS WITH HIV COINFECTION:
Combination Therapy: 180 mcg subcutaneously once a week

Duration of therapy:
-When used with other HCV antiviral drugs: The manufacturer product information of the other HCV antiviral drugs should be consulted.
-When used with ribavirin without other HCV antiviral drugs: 48 weeks, regardless of HCV genotype

COMMENTS:
-The manufacturer product information for coadministered HCV antiviral drugs should be consulted.
-This drug should not be used alone or in combination with ribavirin without additional HCV antiviral drugs for treatment of chronic hepatitis C (CHC) patients who failed prior interferon alfa therapy.
-This drug is not recommended for treatment of CHC patients who have had solid organ transplantation.
-Therapy should be discontinued at once if hepatic decompensation occurs.

USE: For the treatment of CHC patients (with or without HIV coinfection) with compensated liver disease
-As part of a combination regimen with other HCV antiviral drugs
-As monotherapy if contraindications or significant intolerance to other HCV antiviral drugs

Usual Adult Dose for Chronic Hepatitis B:

180 mcg subcutaneously once a week for 48 weeks

Use: For the treatment of patients with HBeAG-positive and HBeAG-negative chronic hepatitis B who have compensated liver disease and evidence of viral replication and liver inflammation

Usual Pediatric Dose for Chronic Hepatitis C:

5 years or older: 180 mcg/1.73 m2 x BSA subcutaneously once a week
Maximum dose: 180 mcg

Duration of therapy:
-HCV genotypes 2, 3: 24 weeks
-Other HCV genotypes: 48 weeks

Comments:
-For use with ribavirin
-The manufacturer product information for ribavirin should be consulted.
-Patients who start therapy before their 18th birthday should remain on the recommended pediatric dose until therapy is finished.

Use: In combination with ribavirin, for the treatment of CHC patients with compensated liver disease

• Pegasys
• Pegasys ProClick

Hypersensitivity reactions (eg, urticaria, angioedema, bronchoconstriction, anaphylaxis, Stevens-Johnson syndrome) to peginterferon alfa-2a, other alfa interferons, or any component of the formulation; autoimmune hepatitis; hepatic decompensation in cirrhotic patients (Child-Pugh score >6, class B and C) before treatment; hepatic decompensation with Child-Pugh score ≥6 in cirrhotic CHC coinfected with HIV before treatment; neonates and infants (due to benzyl alcohol component)

Combination therapy with peginterferon alfa-2a and ribavirin is also contraindicated in pregnancy; men whose female partners are pregnant

Documentation of allergenic cross-reactivity for interferons is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty

Aldesleukin: Interferons (Alfa) may enhance the adverse/toxic effect of Aldesleukin. In particular, risks of myocardial and renal toxicity may be increased by this combination. Consider therapy modification

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Methadone: Interferons (Alfa) may increase the serum concentration of Methadone. Monitor therapy

Pegloticase: May diminish the therapeutic effect of Peginterferon Alfa-2a. Monitor therapy

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Ribavirin (Oral Inhalation): Interferons (Alfa) may enhance the adverse/toxic effect of Ribavirin (Oral Inhalation). Hemolytic anemia has been observed. Monitor therapy

Ribavirin (Systemic): Interferons (Alfa) may enhance the adverse/toxic effect of Ribavirin (Systemic). Hemolytic anemia has been observed. Monitor therapy

Telbivudine: Peginterferon Alfa-2a may enhance the adverse/toxic effect of Telbivudine. Specifically, the risk for peripheral neuropathy may be increased. Avoid combination

Theophylline Derivatives: Interferons may decrease the metabolism of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification

Zidovudine: Interferons may enhance the adverse/toxic effect of Zidovudine. Interferons may decrease the metabolism of Zidovudine. Monitor therapy

Manufacturer’s labeling:

Clinical studies tested as follows:

Children: Hematologic and biochemical assessments were made at weeks 1, 3, 5, and 8, and then every 4 weeks thereafter; TSH measured every 12 weeks

Adults: CBC (including hemoglobin, WBC, and platelets) and chemistries (including liver function tests and uric acid) measured at weeks 1, 2, 4, 6, and 8, and then every 4-6 weeks (more frequently if abnormal); TSH measured every 12 weeks.

In addition, the following baseline values were used as entrance criteria in adults:

Platelet count ≥90,000/mm3 (as low as 75,000/mm3 in patients with cirrhosis or 70,000/mm3 in patients with CHC coinfected with HIV)

ANC ≥1500/mm3

Serum creatinine <1.5 times ULN

TSH and T4 within normal limits or adequately controlled

CD4+ cell count ≥200 cells/mm3 or CD4+ cell count ≥100 cells/mm3, but <200 cells/mm3 and HIV-1 RNA <5000 copies/mL in CHC patients coinfected with HIV

Hemoglobin ≥12 g/dL for women and ≥13 g/dL for men in CHC monoinfected patients

Hemoglobin ≥11 g/dL for women and ≥12 g/dL for men in CHC patients coinfected with HIV

Serum HCV RNA levels (pretreatment, 12- and 24 weeks after therapy initiation, 24 weeks after completion of therapy). Note: Discontinuation of therapy may be considered after 12 weeks in patients with HCV (genotype 1) who fail to achieve an early virologic response (EVR) (defined as ≥2-log decrease in HCV RNA compared to pretreatment) or after 24 weeks with detectable HCV RNA. Treat patients with HCV (genotypes 2,3) for 24 weeks (if tolerated) and then evaluate HCV RNA levels (Ghany, 2009).

Prior to treatment, pregnancy screening should occur for women of childbearing age who are receiving treatment or who have male partners who are receiving treatment. In combination therapy with ribavirin, pregnancy tests should continue monthly up to 6 months after discontinuation of therapy. Evaluate for depression and other psychiatric symptoms before and during therapy; baseline eye examination and periodically in patients with baseline disorders; baseline echocardiogram in patients with cardiac disease. In children, growth velocity and weight should be monitored during and periodically after combination therapy is discontinued.

Alternate recommendations (AASLD/IDSA 2015): Chronic Hepatitis C:

Baseline (within 12 weeks prior to starting antiviral therapy): CBC, INR, hepatic function panel (albumin, total and direct bilirubin, ALT, AST, and alkaline phosphatase), calculated GFR.

Baseline (at any time prior to starting antiviral therapy): HCV genotype and subtype, quantitative HCV viral load.

During therapy: CBC, serum creatinine, calculated GFR, hepatic function panel (after 4 weeks of therapy and as clinically indicated); quantitative HCV viral load testing (after 4 weeks of therapy and at 12 weeks after completion of therapy). If quantitative HCV viral load is detectable at treatment week 4, repeat testing is recommended after 2 additional weeks of treatment (treatment week 6).

Alternate recommendations (AASLD [Terrault 2016]): Chronic Hepatitis B:

During therapy: CBC (monthly to every 3 months); TSH (every 3 months); monitor for autoimmune, ischemic, neuropsychiatric, and infectious complications.