PegIntron

Treatment should be initiated and monitored only by a physician experienced in the management of patients with hepatitis C. Posology PegIntron should be administered as a once weekly subcutaneous injection. The dose administered in adults depends on whether it is used in combination therapy (bitherapy or tritherapy) or as monotherapy.

PegIntron combination therapy (bitherapy or tritherapy) Bitherapy (PegIntron with ribavirin): applies to all adult and paediatric patients 3 years of age and older. Tritherapy (PegIntron with ribavirin and boceprevir): applies to adult patients with genotype 1 CHC.

5 micrograms/kg/week in combination with ribavirin capsules. 5 g/kg of PegIntron to be used in combination with ribavirin may be delivered in weight categories with the PegIntron strengths according to Table 1. 5 1,400 7d a: 2 morning, 2 evening b: 2 morning, 3 evening c: 3 morning, 3 evening d: 3 morning, 4 evening * Refer to the SmPC of boceprevir for details about the dose of boceprevir to be administered in tritherapy.

Adults - Duration of treatment – Naïve patients Tritherapy:

Refer to the SmPC for boceprevir. 1). , a total of 48 weeks). e. a total of 48 weeks). However, if HCV-RNA is still detectable at treatment week 24, discontinuation of therapy should be considered. e. overall 48 weeks treatment duration).

1).  Genotypes 2 or 3: It is recommended that all patients be treated with bitherapy for 24 weeks, except for HCV/HIV co-infected patients who should receive 48 weeks of treatment.  Genotype 4: In general, patients infected with genotype 4 are considered harder to treat and limited study data (n=66) indicate they are compatible with a duration of treatment with bitherapy as for genotype 1.

Adults - Duration of treatment - HCV/HIV co-infection Bitherapy:

The recommended duration of treatment for HCV/HIV co-infected patients is 48 weeks with bitherapy, regardless of genotype. Predictability of response and non-response in HCV/HIV co-infection - Early virological response by week 12, defined as a 2 log viral load decrease or undetectable levels of HCV-RNA, has been shown to be predictive for sustained response.

1). A positive predictive value of 50 % (52/104; Study 1) was observed for HCV/HIV co-infected patients receiving bitherapy.

Adults Tritherapy Refer to the SmPC for boceprevir. Bitherapy and monotherapy Summary of the safety profile The most common treatment-related adverse reactions reported during clinical trials with PegIntron in combination with ribavirin in adults, seen in more than half of the study subjects, were fatigue, headache, and injection site reaction.

Additional adverse reactions reported in more than 25 % of subjects included nausea, chills, insomnia, anaemia, pyrexia, myalgia, asthenia, pain, alopecia, anorexia, weight decreased, depression, rash and irritability. The most frequently reported adverse reactions were mostly mild to moderate in severity and were manageable without the need for modification of doses or discontinuation of therapy.

Fatigue, alopecia, pruritus, nausea, anorexia, weight decreased, irritability and insomnia occur at a notably lower rate in patients treated with PegIntron monotherapy compared to those treated with combination therapy (see Table 6).

Tabulated summary of adverse reactions The following treatment-related adverse reactions were reported in adults in clinical trials or through post-marketing surveillance in patients treated with peginterferon alfa-2b, including PegIntron monotherapy or PegIntron/ribavirin.

These reactions are listed in table 6 by system organ class and frequency (very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) or not known (cannot be estimated from the available data).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Table 6 Adverse reactions reported in adults in clinical trials or through post-marketing surveillance in patients treated with peginterferon alfa-2b, including PegIntron monotherapy or PegIntron + ribavirin Infections and infestations Very common: Viral infection*, pharyngitis* Common: Bacterial infection (including sepsis), fungal infection, influenza, upper respiratory tract infection, bronchitis, herpes simplex, sinusitis, otitis media, rhinitis Uncommon: Injection site infection, lower respiratory tract infection Not known: Hepatitis B reactivation in HCV/HBV co-infected patientsMedicinal product no longer authorised 18 Blood and lymphatic system disorders Very common: Anaemia, neutropenia Common: Haemolytic anaemia, leukopenia, thrombocytopenia, lymphadenopathy Very rare: Aplastic anaemia Not known: Aplasia pure red cell Immune system disorders Uncommon: Drug hypersensitivity Rare: Sarcoidosis Not known: Acute hypersensitivity reactions including angioedema, anaphylaxis and anaphylactic reactions including anaphylactic shock, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, systemic lupus erythematosus Endocrine disorders Common: Hypothyroidism, hyperthyroidism Metabolism and nutrition disorders Very common: Anorexia Common: Hypocalcemia, hyperuricemia, dehydration, increased appetite Uncommon: Diabetes mellitus, hypertriglyceridaemia Rare: Diabetic ketoacidosis Psychiatric disorders Very common: Depression, anxiety*, emotional lability*, concentration impaired, insomnia Common: Aggression, agitation, anger, mood altered, abnormal behaviour, nervousness, sleep disorder, libido decreased, apathy, abnormal dreams, crying Uncommon: Suicide, suicide attempt, suicidal ideation, psychosis, hallucination, panic attack Rare: Bipolar disorders Not known: Homicidal ideation, mania Nervous system disorders Very common: Headache, dizziness Common: Amnesia, memory impairment, syncope, migraine, ataxia, confusion, neuralgia, paraesthesia, hypoaesthesia, hyperaesthesia, hypertonia, somnolence, disturbance in attention, tremor, dysgeusia Uncommon: Neuropathy, neuropathy peripheral Rare: Convulsion Very rare: Cerebrovascular haemorrhage, cerebrovascular ischaemia, encephalopathy Not known: Facial palsy, mononeuropathies Eye disorders Common: Visual disturbance, vision blurred, photophobia, conjunctivitis, eye irritation, lacrimal disorder, eye pain, dry eye Uncommon: Retinal exudates Rare: Loss of visual acuity or visual fields, retinal haemorrhage, retinopathy, retinal artery occlusion, retinal vein occlusion, optic neuritis, papilloedema, macular oedema Not known: Serous retinal detachment Ear and labyrinth disorders Common: Hearing impaired/loss, tinnitus, vertigoMedicinal product no longer authorised 19 Uncommon Ear pain Cardiac disorders Common: Palpitations, tachycardia Uncommon: Myocardial infarction Rare: Congestive heart failure, cardiomyopathy, arrhythmia, pericarditis Very rare: Cardiac ischaemia Not known: Pericardial effusion Vascular disorders Common: Hypotension, hypertension, flushing Rare: Vasculitis Respiratory, thoracic and mediastinal disorders Very common: Dyspnoea*, cough* Common: Dysphonia, epistaxis, respiratory disorder, respiratory tract congestion, sinus congestion, nasal congestion, rhinorrhea, increased upper airway secretion, pharyngolaryngeal pain Very rare: Interstitial lung disease Not known: Pulmonary fibrosis, pulmonary arterial hypertension# Gastrointestinal disorders Very common: Vomiting*, nausea, abdominal pain, diarrhoea, dry mouth* Common: Dyspepsia, gastroesophageal reflux disease, stomatitis, mouth ulceration, glossodynia, gingival bleeding, constipation, flatulence, haemorrhoids, cheilitis, abdominal distension, gingivitis, glossitis, tooth disorder Uncommon: Pancreatitis, oral pain Rare: Colitis ischaemic Very rare: Colitis ulcerative Not known Tongue pigmentation Hepatobiliary disorders Common: Hyperbilirubinemia, hepatomegaly Skin and subcutaneous tissue disorders Very common: Alopecia, pruritus*, dry skin*, rash* Common: Psoriasis, photosensitivity reaction, rash maculo-papular, dermatitis, erythematous rash, eczema, night sweats, hyperhidrosis, acne, furuncle, erythema, urticaria, abnormal hair texture, nail disorder Rare: Cutaneous sarcoidosis Very rare: Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema […]

Psychiatric and Central Nervous System (CNS) Severe CNS effects, particularly depression, suicidal ideation and attempted suicide have been observed in some patients during PegIntron 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 alpha 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 or homicidal ideation is identified, it is recommended that treatment with PegIntron be discontinued, and the patient followed, with psychiatric intervention as appropriate.

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

3). 4 % vs 1 %) during treatment and during the 6-month follow-up after treatment. g. depression, emotional lability, and somnolence). Patients with substance use/abuse HCV infected patients having a co-occurring substance use disorder (alcohol, cannabis, etc) are at an increased risk of developing psychiatric disorders or exacerbation of already existing psychiatric disorders when treated with alpha interferon.

If treatment with alpha interferon is judged necessary in these patients, the presence of psychiatric co-morbidities and the potential for other substance use should be carefully assessed and adequately managed before initiating therapy.

4); - Severe, debilitating medical conditions; - Autoimmune hepatitis or a history of autoimmune disease; - Severe hepatic dysfunction or decompensated cirrhosis of the liver; - Pre-existing thyroid disease unless it can be controlled with conventional treatment; - Epilepsy and/or compromised central nervous system (CNS) function; - HCV/HIV patients with cirrhosis and a Child-Pugh score ≥ 6.

- Combination of PegIntron with telbivudine. Paediatric population - Existence of, or history of severe psychiatric condition, particularly severe depression, suicidal ideation or suicidal attempt. Medicinal product no longer authorised 10