Peginterferon Alfa-2A

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications:

• HBeAg-positive and HBeAg-negative chronic hepatitis B in non-cirrhotic and mildly cirrhotic patients (Child-Pugh A) with compensated liver disease and evidence of viral replication and liver inflammation
• Chronic hepatitis C, in combination with ribavirin, in non-cirrhotic and mildly cirrhotic adults patients (Child-Pugh A) with elevated transaminases and compensated liver disease

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to alfa interferons
• Hypersensitivity to E.coli-derived products
• Pregnancy (when combined with ribavirin)
• Breastfeeding (when combined with ribavirin)
• Severe hepatic impairment
• Decompensated cirrhosis of the liver
• Autoimmune hepatitis
• History of severe pre-existing cardiac disease
• HIV-HCV patients with cirrhosis and a Child-Pugh score ≥ 6
• Children < 3 years
• In paediatric patients, the presence of, or history of severe psychiatric condition, particularly severe depression, suicidal ideation or suicidal attempt
• Coadministration with telbivudine

Cautions

• Pregnancy
• Breastfeeding
• Severe renal impairment
• Children
• Patients with existence of, or history of severe psychiatric conditions
• Patients with history of substance abuse
• Diabetes mellitus
• Hypoglycaemia
• Hyperglycaemia
• Preexisting cardiac abnormalities
• Preexisting thyroid disorders
• Cardiovascular disease
• Anaemia
• Patients predisposed to the development of autoimmune disorders
• Preexisting ophthalmologic disorders
• Psoriasis
• Sarcoidosis
• History of organ transplant
• Patients co-infected with HIV and receiving Highly Active Anti-Retroviral Therapy (HAART)
• Patients with a low CD4 count
• Long-term peginterferon alfa-2a maintenance monotherapy
• Dental and periodontal disorders
• May impair the ability to drive or operate machinery

Forms avail. in SA and covered in this monograph: inj

Chronic hepatitis B
- HBeAg-positive and HBeAg- negative chronic hepatitis B in patients with compensated liver disease and evidence of viral replication, increased alanine aminotransferase (ALT) and histologically verified liver inflammation and/or fibrosis
- HBeAg-positive and HBeAg- negative chronic hepatitis B in non-cirrhotic and mildly cirrhotic patients (Child-Pugh A) with compensated liver disease and evidence of viral replication and liver inflammation

• SC: 180μg, weekly; Treatment duration: 48 weeks

Chronic hepatitis C for treatment-naive patients (additional agent required)
- In patients with compensated liver disease
- In non-cirrhotic and mildly cirrhotic patients in whom transaminases are elevated and who have compensated liver disease

• SC: 180μg, weekly; Treatment duration: 24-48 weeks

Monotherapy for hepatitis C should only be considered in case of contraindication to other medicinal products

Duration of combination therapy with additional agent (ribavirin) for CHC depends on viral genotype. Patients infected with HCV genotype 1 with detectable HCV RNA at week 4 regardless of pre-treatment viral load should receive 48 weeks of therapy

Chronic hepatitis C for treatment-experienced patients (additional agent required)
- In patients with compensated liver disease
- In non-cirrhotic and mildly cirrhotic patients in whom transaminases are elevated and who have compensated liver disease

• SC: 180μg, weekly; Treatment duration: 48-72 weeks

Patients who have detectable virus at week 12 should stop therapy

The recommended total duration of therapy is 48 weeks

Patients infected with virus genotype 1, not responding to prior treatment with peginterferon and ribavirin are considered for treatment, the recommended total duration of therapy is 72 weeks

Chronic hepatitis C co-infection with HIV

• SC: 180μg, weekly; Treatment duration: 48 weeks

The duration of combination therapy should be individualised based on the patient's viral genotype _3,5

Administer into abdomen or thigh

Dose adjustment to 135 μg may be required for moderate to severe adverse reactions. Dose increase to original dose may be considered when the adverse reaction abates

Treatment should be initiated only by a physician experienced in the treatment of patients with hepatitis B or C

See Additional Prescribing Points

Not established for use in South Africa for children below 18 years

Younger than 3 years

• Contraindicated

Between 3-17 years with chronic hepatitis B
- HBeAg-positive chronic hepatitis B (CHB) in non-cirrhotic children and adolescents with evidence of viral replication and persistently elevated serum ALT levels

Before initiating therapy for CHB, persistently elevated serum ALT levels should have been documented. The response rate is lower in patients with no to minimal increase in ALT level at baseline

Between 5-17 years with chronic hepatitis C
- In treatment-naïve children and adolescents who are positive for serum hepatitis C virus (HCV)-RNA

(See Additional Prescribing Points)

Treatment duration in combination therapy typically should be between 24-48 weeks depending on the viral gentotype

Patients who still have detectable levels of HCV-RNA despite an initial 24 weeks of therapy, should discontinue therapy, as it is unlikely they will be able to achieve a sustained virological response with continued therapy

If treatment is initiated prior to their 18th birthday, paediatric dosing should be maintained through treatment completion

To calculate BSA, it is recommended to use Mosteller's equation

Pregnancy

• Peginterferon alfa-2a: Caution; not recommended
  Peginterferon alfa-2a + ribavirin: Contraindicated
• There is no or a limited amount of data from the use of peginterferon alfa-2a in pregnant women
• Studies in animals with interferon alfa-2a have shown reproductive toxicity and the potential risk for humans is unknown. Peginterferon alfa-2a is to be used during pregnancy only if the potential benefit justifies the potential risk to the foetus
• Peginterferon + ribavirin: Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin
• Extreme care must be taken to avoid pregnancy in female patients or in partners of male patients taking peginterferon alfa-2a in combination with ribavirin

Breastfeeding

• Peginterferon alfa-2a: Caution; not recommended
  Peginterferon alfa-2a + ribavirin: Contraindicated
• It is unknown whether peginterferon alfa-2a or its metabolites are excreted in human milk
• Because of the potential for adverse reactions in breastfed infants, breastfeeding should be discontinued prior to initiation of treatment

Fertility

• There is no data on the effects of peginterferon alfa-2a on fertility in women. A prolongation of the menstrual cycle has been seen with peginterferon alfa-2a in female monkeys
• Peginterferon + ribavirin: Female patients of childbearing potential must use an effective contraceptive during treatments and for 4 months after treatment has been concluded. Male patients or their female partners must use an effective contraceptive during treatment and for 7 months after treatment has concluded

Renal Impairment

• Mild to moderate (eGFR > 30ml/min/1.73m²): No dose adjustment recommended 
• Severe (eGFR < 29/ml/min/1.73m²): Caution; dose adjustment recommended
  A reduced dose of SC: 135mcg, weekly is recommended

Hepatic Impairment

• Mild (Child-Pugh Class A): No dose adjustment recommended
  No dose adjustment needed as therapy is intiated. If an isolated increase in ALT observed, reduce dose to 135mcg, weekly. Discontinue therapy when the increase in ALT levels is progressive (X10 ULN) and/or patient is clinically hepatic decompensated
• Moderate to severe (Child-Pugh Classes B & C): Contraindicated

Elderly         

• No dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Depression
• Anxiety
• Hallucination
• Abnormal behaviour
• Attention deficit / hyperactivity disorder
• Insomnia
• Aggression
• Mood alteration
• Emotional disorders
• Nervousness
• Decreased libido
• Suicidal ideation
• Hallucinations
• Suicide
• Psychotic disorder
• Mania
• Bipolar disorders
• Homicidal ideation
• Headache
• Dizziness
• Impaired concentration
• Migraine
• Syncope
• Memory impairment
• Weakness
• Hypoaesthesia
• Hyperaesthesia
• Paraesthesia
• Tremor
• Nightmares
• Somnolence
• Peripheral neuropathy
• Coma
• Seizures
• Facial palsy
• Cerebral ischaemia
• Fatigue
• Irritability 
• Cerebral haemorrhage

Cardiovascular Disorders

• Tachycardia
• Peripheral oedema
• Palpitations
• Myocardial infarction
• Congestive cardiac failure
• Cardiomyopathy
• Angina
• Arrhythmia
• Atrial fibrillation
• Pericarditis
• Supraventricular tachycardia
• Hypertension
• Vasculitis
• Peripheral ischaemia
• Chest pain
• Endocarditis

Respiratory Disorders

• Dyspnoea
• Cough
• Epistaxis
• Nasopharyngitis
• Sinus congestion
• Nasal congestion
• Rhinitis
• Sore throat
• Wheezing
• Interstitial pneumonitis
• Pulmonary embolism
• Pulmonary arterial hypertension
• Bronchitis
• Upper respiratory infection
• Pneumonia
• Nasopharyngitis
• Streptococcal pharyngitis 

Gastrointestinal Disorders

• Diarrhoea
• Nausea and vomiting
• Abdominal pain
• Dyspepsia
• Dysphagia
• Mouth ulceration
• Gingival bleeding
• Glossitis
• Stomatitis
• Flatulence
• Dry mouth
• Gastrointestinal bleeding
• Aphthous stomatitis
• Oral disorder
• Peptic ulcer
• Pancreatitis
• Ischaemic colitis
• Tongue pigmentation
• Oral candidiasis
• Gastroenteritis 
• Tooth abscess

Hepatobiliary Disorders

• Hepatic dysfunction
• Hepatic failure
• Cholangitis
• Fatty liver
• Hepatic neoplasm

Genitourinary Disorders

• Renal insufficiency          
• Dysuria
• Incontinence
• Impotence
• Vaginal discharge
• Urinary tract disorder

Endocrine and Metabolic Disorders

• Dehydration
• Hypothyroidism
• Hyperthyroidism
• Diabetes
• Diabetic ketoacidosis
• Anorexia
• Decreased weight
• Decreased appetite
• Hot flushes
• Thirst

Musculoskeletal Disorders

• Myalgia
• Arthralgia
• Back pain
• Arthritis
• Muscle weakness
• Bone pain
• Neck pain
• Musculoskeletal pain
• Muscle cramps
• Myositis
• Rhabdomyolysis

Skin and Subcutaneous Tissue Disorders

• Alopecia
• Dermatitis
• Pruritis
• Dry skin
• Psoriasis
• Urticaria
• Eczema
• Rash
• Increased sweating
• Photosensitivity reaction
• Night sweats
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Angioedema
• Erythema multiforme
• Skin infection
• Injection site reaction
• Vessel puncture site haematoma
• Flushing
• Swollen face
• Drug eruption

Immune, Blood and Lymphatic System Disorders

• Thrombocytopenia
• Anaemia
• Lymphadenopathy
• Pancytopenia
• Aplastic anaemia
• Pure red cell aplasia
• Sarcoidosis
• Thyroiditis
• Anaphylaxis
• Systemic lupus erythematosus
• Rheumatoid arthritis
• Idiopathic or thrombotic thrombocytopenic purpura
• Liver and renal graft rejection
• Vogt-Koyanagi-Harada disease
• Sepsis
• Infectious mononucleosis
• Herpes simplex
• Fungal, viral and bacterial infections
• Influenza
• Candidiasis
• Fever
• Rigors
• Influenza-like illness

Sensory Disorders

• Vertigo
• Ear pain
• Hearing loss
• Blurred vision
• Eye pain
• Eye inflammation
• Xerophthalmia
• Retinal haemorrhage
• Blindness transient
• Retinal exudates
• Visual impairment
• Eye irritation
• Eye pruritis
• Optic neuropathy
• Papilloedema
• Retinal vascular disorder
• Retinopathy
• Corneal ulcer
• Vision loss
• Serous retinal detachment
• Otitis externa
• Taste disturbance

Other

• Abnormal psychiatric evaluation
• Tooth abscess
• Educational problem (paediatric patients)

• Theophylline 
• Methadone 
• Ribavirin
• Azathioprine 
• Telbivudine 
• Myelosuppressive agents
• Didanosine (when used in combination with ribavirin)
• Zidovudine (when used in combination with ribavirin)

• Full blood count with differential
• Hepatic function
• Uric acid
• Renal function
• Thyroid function
• ECG
• Ophthalmic examination
• Psychiatric evaluation

Specific cases may require

• CD4 count
• Echocardiogram
• Growth velocity and weight (children)

Prolonged duration of peginterferfon alfa-2a treatment

Treatment for 24 weeks may be considered in patients infected with:

• genotype 1 with low viral load (LVL) (≤ 800,000 IU/ml) at baseline or
• genotype 4

Use of peginterferon alfa-2a as long term maintenance monotherapy (unapproved use of)

• In an RCT study (HALT-C) of HCV non-responder patients with varied degrees of fibrosis where 3.5 years of treatment with 90 micrograms/week of peginterferon alfa-2a monotherapy was studied, no significant reductions were observed in the rate of fibrosis progression or related clinical events

Peginterferon alfa-2a dose modification recommendations in paediatric patients with chronic hepatitis B or chronic hepatitis C

• For paediatric patients, based on toxicities, up to three levels of dose modification can be made before dose interruption or discontinuation is considered (see table below)

The conjugation of PEG reagent (bis-monomethoxypolyethylene glycol) to interferon alfa-2A forms a pegylated interferon alfa-2A. Peginterferon alfa-2A possesses the in vitro antiviral and antiproliferative activities that are characteristic of interferon alfa-2A. Interferons bind to specific receptors on the cell surface initiating a complex intracellular signaling pathway and rapid activation of gene transcription. Interferon-stimulated genes modulate many biological effects including the inhibition of viral replication in infected cells, inhibition of cell proliferation and immunomodulation.

Injection (per 0.5ml) 135μg

• Pegasys (Roche) originator

Injection (per 0.5ml) 180μg

• Pegasys (Roche) originator