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Peginterferon alfa 2a parenteral

Updated 2 Feb 2023 | Interferon alfa

Presentation

Solution for injection containing peginterferon alfa-2a.

The potency should not be compared to other proteins of the same class, whether pegylated or not.

These products have been produced by recombinant technology using E.coli.

Drugs List

  • PEGASYS 135microgram/0.5ml solution for injection pre-filled syringe
  • PEGASYS 180microgram/0.5ml solution for injection pre-filled syringe
  • PEGASYS 90microgram/0.5ml solution for injection pre-filled syringe
  • peginterferon alfa-2a 135microgram/0.5ml solution for injection pre-filled syringe
  • peginterferon alfa-2a 180microgram/0.5ml solution for injection pre-filled syringe
  • peginterferon alfa-2a 90microgram/0.5ml solution for injection pre-filled syringe
  • Therapeutic Indications

    Uses

    Chronic hepatitis C - in combination with ribavirin
    Chronic hepatitis C - Monotherapy if ribavirin is contraindicated
    HBeAg-negative chronic hepatitis B with compensated liver disease
    HBeAg-positive chronic hepatitis B with compensated liver disease
    HBeAg-positive chronic hepatitis B without cirrhosis

    Treatment of HBeAg-positive or HBeAg-negative chronic hepatitis B in adults with compensated liver disease and evidence of viral replication, increased ALT and histologically verified liver inflammation and/or fibrosis.

    Treatment of HBeAg-positive chronic hepatitis B in non-cirrhotic children and adolescents 3 years and over with evidence of viral replication and persistently elevated serum ALT levels.

    Treatment of chronic hepatitis C in adult patients who are positive for HCV-RNA, including patients with compensated cirrhosis and/or co-infection with clinically stable HIV.

    Treatment of chronic hepatitis C in adults in conjunction with ribavirin. This combination is indicated in previously untreated patients as well as those who have failed previous treatment with interferon alfa (pegylated or non-pegylated) alone or in combination with ribavirin.

    Treatment of chronic hepatitis C in adults as monotherapy in cases where ribavirin is not tolerated or is contraindicated.

    Treatment of chronic hepatitis C in treatment-naive children and adolescents 5 years and over who are positive for HCV-RNA, in combination with ribavirin.

    Dosage

    Treatment should be initiated and supervised by a specialist.

    Prescribing information for ribavirin should be consulted if combination therapy is to be used.

    Adults

    Chronic hepatitis B: HBeAg-positive and HBeAg-negative chronic hepatitis B
    180 micrograms once weekly for 48 weeks.

    Chronic hepatitis C
    180 micrograms once weekly as monotherapy or in combination with oral ribavirin.

    Duration of treatment: Chronic hepatitis C - treatment naive patients:
    Monotherapy: continue for 48 weeks.

    Combination therapy (with ribavirin)
    Duration of treatment depends on viral genotype and may be guided by viral load at baseline, viral response, tolerability to combination therapy and additional prognostic factors such as degree of fibrosis. The 24 week treatment duration may be associated with a higher risk of relapse than a 48 week treatment duration.

    Genotype 1
    Genotype 1 with low viral load (equal to or less than 800,000 IU/ml) at baseline, consider 24 week or 48 week duration.
    Genotype 1 with high viral load (greater than 800,000 IU/ml) at baseline, who become HCV RNA negative at week 4 and remain HCV RNA negative at week 24, continue for 48 week duration. Shortening the treatment duration in these patients should be considered with even more caution since the limited data available suggest that this may significantly negatively impact the sustained virologic response.
    Genotype 1 with detectable HCV RNA at week 4 regardless of pre-treatment viral load, continue for 48 week duration.

    Genotype 2 or 3
    Genotype 2 or 3 with low viral load (equal to or less than 800,000 IU/ml) and who become HCV RNA negative by week 4 of treatment and who remain negative at week 16, consider 16 week or 24 week duration. This duration may be associated with a lower chance of response and is associated with a higher risk of relapse than 24 weeks of treatment.
    Genotype 2 or 3 with high viral load (greater than 800,000 IU/ml) at baseline who become HCV RNA negative at week 4, continue for 24 weeks. Shortening the treatment duration in these patients should be considered with even more caution since the limited data available suggest that this may significantly negatively impact the sustained virologic response.
    Genotype 2 or 3 with detectable HCV RNA at week 4 regardless of pre-treatment viral load, continue for 24 week duration.

    Genotype 4
    Genotype 4, regardless of pre-treatment viral load, who become HCV RNA negative at week 4 and remain HCV RNA negative at week 24, consider 24 week or 48 week duration.
    Genotype 4, regardless of pre-treatment viral load, who do not become HCV RNA negative at week 4 and are not HCV RNA negative at week 24, continue for 48 week duration.

    Genotype 5 or 6
    Available data are limited. Treatment for 48 weeks is recommended.

    Duration of treatment: Chronic hepatitis C- treatment experienced patients:
    Duration of therapy is 48 weeks. Patients who have detectable virus at week 12 should stop therapy.
    If genotype 1 patients, who have not previously responded to peginterferon alfa 2a and ribavirin are considered for treatment, the recommended total duration of therapy is 72 weeks.

    HIV-HCV co-infection
    Regardless of HVC genotype the recommended dose is 180 micrograms once weekly for 48 weeks as monotherapy or in combination with ribavirin.

    Children

    Contraindicated in neonates and young children up to 3 years due to the benzyl alcohol content in the injection.

    Children should be treated after the pubertal growth spurt whenever possible in order to reduce the risk of growth inhibition.

    Chronic hepatitis B
    Children 3 to 18 years with body surface area (BSA) greater than 0.54 meters squared:
    BSA 0.54 to 0.74 dosage 65 micrograms once weekly.
    BSA 0.75 to 1.08 dosage 90 micrograms once weekly.
    BSA 1.09 to 1.51 dosage 135 micrograms once weekly.
    BSA greater than 1.51 dosage 180 micrograms once weekly.

    Duration of treatment: 48 weeks.

    Chronic hepatitis C in combination with ribavirin
    Children 5 to 18 years with body surface area (BSA) greater than 0.71 metres squared:
    BSA 0.71 to 0.74 dosage 65 micrograms once weekly.
    BSA 0.75 to 1.08 dosage 90 micrograms once weekly.
    BSA 1.09 to 1.51 dosage 135 micrograms once weekly.
    BSA greater than 1.51 dosage 180 micrograms once weekly.

    Duration of treatment
    Genotype 1: 48 weeks.
    Genotype 2 or 3: 24 weeks.
    Genotype 4: 48 weeks.
    Genotype 5 or 6: Available data are limited. Treatment for 48 weeks is recommended.

    If HCV RNA is still detectable after 24 weeks of treatment, discontinue. It is unlikely continuation will achieve sustained virological response.

    Patients with Renal Impairment

    Severe renal impairment or end stage renal disease: 135 micrograms once weekly.

    Additional Dosage Information

    Adult dose adjustment for adverse reactions

    Moderate to severe adverse reactions: Initial dose reduction to 135 micrograms once weekly is generally adequate. However, in some cases dose reduction to 90 micrograms once weekly or 45 micrograms once weekly is necessary. Dose increases to or towards the original dose may be considered when the adverse reaction abates.

    Haematological adverse reactions
    Absolute neutrophil count is 500 to less than 750cells/cubic millimetre: reduce dose.
    Absolute neutrophil count less than 500cells/cubic millimetre: suspend treatment until absolute neutrophil count returns to greater than 1000cells/cubic millimetre. Restart treatment 90 micrograms once weekly and monitor neutrophil count.

    Platelet count is 25,000 to less than 50,000cells/cubic millimetre: reduce dose to 90 micrograms once weekly.
    Platelet count below 25,000cells/cubic millimetre: discontinue.

    For specific recommendations for the management of treatment-emergent anaemia from combination with ribavirin - refer to manufacturers product information for further details.

    In case of intolerance to ribavirin, peginterferon alfa-2a monotherapy should be continued.

    Hepatic adverse reactions

    Hepatitis B:
    Treatment should not be initiated if ALT is greater than 10 x ULN.

    Treatment continuation with more frequent liver function monitoring should be considered during ALT flares.

    If dose is reduced, or treatment withheld, therapy may be restored when flare is subsiding.

    Hepatitis C:
    If ALT increase is progressive or persistent, reduce the dose to 135 micrograms once weekly. If an increase in the ALT levels is progressive despite dose reduction or is accompanied by increased bilirubin or evidence of hepatic decompensation, treatment should be discontinued.

    Paediatric dose adjustment for adverse reactions

    Adverse effects may result in the need for differing degrees of dose reduction before interruption or discontinuing treatment. Refer to manufacturers product information for further details.

    Administration

    For subcutaneous injection into the abdomen or thigh.

    Contraindications

    Children under 3 years
    Hypersensitivity to benzyl alcohol
    Neutrophil count below 1.5 x 10 to the power of 9 / L at baseline
    Platelet count below 90 x 10 to the power of 9 / L at baseline
    Autoimmune hepatitis
    Breastfeeding
    Decompensated liver disease
    History of severe cardiac disorder
    History of severe psychiatric disorder in children
    HIV patients with Child-Pugh score above 6
    Pregnancy
    Severe hepatic impairment
    Severe psychiatric disorder in children
    Uncontrolled thyroid disorder

    Precautions and Warnings

    CD4 counts less than 200 cells/microlitre
    Children aged 3 to 18 years
    Organ transplant recipients
    Predisposition to autoimmune disorder
    Alcoholism
    Cardiovascular disorder
    Diabetes mellitus
    Drug misuse
    Hepatic impairment
    History of severe psychiatric disorder
    HIV patients receiving highly active anti-retroviral therapy
    Oesophageal varices
    Psoriasis
    Retinopathy
    Sarcoidosis
    Severe psychiatric disorder
    Severe renal impairment
    Thyroid dysfunction

    May exacerbate sarcoidosis
    Reduce dose in patients with severe renal impairment
    Advise ability to drive/operate machinery may be affected by side effects
    Combination therapy with ribavirin-refer to ribavirin prescribing info
    May increase risk of solid organ graft rejection
    Treatment to be initiated and supervised by a specialist
    Contains benzyl alcohol
    Record name and batch number of administered product
    Monitor haematological parameters before and during treatment
    Monitor thyroid function prior to and periodically during treatment
    Perform eye tests before treatment
    Consider reduced/suspend dose if ALT increase severe/progressive/persistent
    Dental check-ups advisable during long-term treatment
    Discontinue if platelet count < 25,000 per cubic mm
    If visual disturbances occur, perform ophthalmic evaluation
    Investigate signs and symptoms suggesting an infection
    Monitor and discontinue if appropriate if psychiatric or CNS problems occur
    Monitor blood glucose periodically
    Monitor closely if HIV co-infection
    Monitor ECG prior to and during treatment in existing cardiac abnormalities
    Monitor hepatic function regularly
    Monitor serum ALT more often in patients developing raised ALT levels
    Monitor serum biochemistry regularly
    Perform periodic eye tests if pre-existing ophthalmic disorder
    Reduce dose if neutrophil count < 750 per cubic mm
    Reduce dose if platelet count < 50,000 per cubic mm
    Review ribavirin dose/use if anaemia develops
    Advise patient to report any new or worsening depression/suicidal ideation
    Advise patient to report incidences of fever
    Advise patient to report symptoms of infection immediately
    Autoimmune diseases may occur during treatment
    Consider stopping treatment if severe uncontrolled infections occur
    Determine TSH levels if patient develops symptoms of thyroid dysfunction
    Discontinue at the onset of severe depression
    May cause growth retardation in children
    May exacerbate psoriasis
    Consider discontinuing if pulmonary function becomes impaired
    Discontinue if blood glucose levels cannot be controlled
    Discontinue if Child Pugh score >6 in HIV patient
    Discontinue if first occurrence or worsening of visual disturbances
    Discontinue if hepatic decompensation develops
    Discontinue if persistent or unexplained pulmonary infiltrates
    Discontinue if psoriasis becomes exacerbated during treatment
    Discontinue if severe hypersensitivity reactions occur
    Discontinue if Vogt-Koyanagi-Harada (VKH) syndrome suspected
    Discontinue in patients showing suicidal behaviour
    Suspend or discontinue therapy if cardiovascular symptoms increase
    Suspend treatment if neutrophil count < 500 cells per cubic mm
    Male & female: Ensure adequate contraception during treatment
    Advise patient of need for high oral hygiene standards
    Advise patient of possible side effects and the need to report them
    If vomiting occurs, rinse mouth thoroughly afterwards

    In paediatric patients document persistently elevated serum ALT levels before initiating therapy for chronic hepatitis B. Studies show the response rate to therapy was lower in patients with no to minimal increase in ALT at baseline.

    Psychiatric effects
    Severe CNS effects, particularly depression, suicidal ideation and attempted suicide have been observed in some patients during peginterferon alfa-2a therapy and even after treatment discontinuation mainly during the 6-month follow-up period. Other CNS effects including aggressive behaviour (sometimes directed against others such as homicidal ideation), bipolar disorders, mania, confusion and alterations of mental status have been observed with alfa interferons. Patients should be closely monitored for any signs or symptoms of psychiatric disorders. If such symptoms appear, the potential seriousness of these undesirable effects must be borne in mind by the prescribing physician and the need for adequate therapeutic management should be considered. If psychiatric symptoms persist or worsen, or suicidal ideation is identified, it is recommended that treatment with peginterferon alfa-2a be discontinued, and the patient followed, with psychiatric intervention as appropriate.

    If treatment with peginterferon alfa-2a is judged necessary in patients with existing or history of severe psychiatric conditions, this should only be initiated after having ensured appropriate individualised diagnostic and therapeutic management of the psychiatric condition.

    Endocrine
    Peginterferon alfa-2a treatment may be initiated or continued if TSH levels can be maintained in the normal range with medication.

    Patients with these conditions who cannot be effectively controlled with medication should not be started on peginterferon alfa-2a therapy. Patients who develop these conditions during treatment and who cannot be controlled with medication should discontinue therapy.

    Co-infection with HIV
    The prescribing information for anti-retroviral products should be consulted to ensure awareness regarding associated toxicities, their overlap with those of peginterferon alfa 2a / ribavirin and their management.

    Pregnancy and Lactation

    Pregnancy

    Peginterferon alfa-2a is contraindicated in pregnancy.

    There is limited data on the use of peginterferon alfa-2a in pregnancy. The potential risk for humans is unknown. Animal studies have shown reproductive toxicity. Peginterferon alfa-2a should only be used in pregnancy if benefit outweighs the potential risk to foetus.

    Additional reference sources do not specify pegylated interferon.

    Briggs (2015) concludes, based on limited data, that maternal administration of interferon alfa does not appear to pose a significant risk to the developing embryo or foetus but because of the antiproliferative action of interferon alfa should be used with caution until more data is available.

    Schaefer (2015) recommends interferon alfa may be used in pregnancy after a benefit-risk assessment.

    Combination therapy with ribavirin: Contraindicated during pregnancy as ribavirin causes serious birth defects (see ribavirin information).

    The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

    Lactation

    Peginterferon alfa-2a is contraindicated in breastfeeding.

    It is unknown if peginterferon alfa-2a or its metabolites are excreted in human breast milk. The manufacturer advises discontinuing breastfeeding prior to treatment.

    Although there is no information available on peginterferon alfa in breast milk, the levels of conventional interferon alfa in breast milk are minuscule. Interferon is poorly absorbed orally and is not likely to reach the blood stream of the infant. It is unlikely peginterferon alfa use presents any serious risk to the breastfed infant.

    Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
    Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

    Side Effects

    Alopecia
    Anaemia
    Anaphylaxis
    Angina
    Angioedema
    Anorexia
    Aplastic anaemia
    Arrhythmias
    Asthenia
    Autoimmune disorders
    Blood dyscrasias
    Blurred vision
    Cardiomyopathy
    Cerebral haemorrhage
    Cholangitis
    Coma
    Concentration disturbances
    Congestive cardiac failure
    Convulsions
    Corneal ulcer
    Cough
    Dehydration
    Depression
    Development of neutralising antibodies
    Diabetes
    Dizziness
    Dysaesthesia
    Dyspnoea
    Electrolyte disturbances
    Epistaxis
    Erythema multiforme
    Eye disorder
    Facial palsy
    Fatigue
    Flushing
    Gastro-intestinal symptoms
    Gastrointestinal bleeding
    Growth retardation (children)
    Headache
    Hearing loss
    Hepatic disorders (fatty changes)
    Hepatic failure
    Hepatic impairment
    Hypertension
    Impotence
    Increase in ALT level
    Infections
    Influenza-like symptoms
    Injection site reactions
    Interstitial pneumonitis
    Ischaemia
    Ischaemic colitis
    Ketoacidosis
    Lymphadenopathy
    Malaise
    Malignant hepatic neoplasm
    Memory disturbances
    Migraine
    Musculoskeletal pain
    Myocardial infarction
    Myositis
    Nightmares
    Palpitations
    Pancreatitis
    Pancytopenia
    Peptic ulceration
    Pericarditis
    Peripheral neuropathy
    Peripheral oedema
    Photosensitivity
    Psychiatric disorders
    Pulmonary embolism
    Pulmonary hypertension
    Pyrexia
    Red cell aplasia
    Renal impairment
    Retinal disturbances
    Rhabdomyolysis
    Rheumatoid arthritis
    Rigors
    Sarcoidosis
    Serum bilirubin increased
    Skin disorder
    Somnolence
    Stevens-Johnson syndrome
    Suicidal tendencies
    Syncope
    Systemic lupus erythematosus
    Taste disturbances
    Thrombocytopenia
    Thrombocytopenic purpura
    Thyroid abnormalities
    Toxic epidermal necrolysis
    Tremor
    Upper respiratory symptoms
    Vasculitis
    Vertigo
    Vogt-Koyanagi- Harada (VKH) syndrome
    Weakness
    Weight loss

    Overdosage

    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

    Further Information

    Last Full Review Date: June 2018

    Reference Sources

    Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

    Summary of Product Characteristics: Pegasys 90mcg, 135mcg and 180mcg solution for injection in Pre-filled Syringe/Pre-filled Pen. Roche Products Ltd. Revised March 2018.

    NICE Evidence Services Available at: www.nice.org.uk Last accessed: 04 May 2018

    US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
    Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
    Peginterferon Alfa Last revised: 02 June 2016
    Last accessed: 30 April 2018

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