BESREMI 250MCG/0.5ML Solution for injection in pre-filled pen

Traceability In order to improve the traceability of biological medicinal products, the name and batch number of the administered product should be clearly recorded. Titration phase The recommended dosing of ropeginterferon alfa-2b during the titration phase (see section 4.2) results in a slower (compared to hydroxycarbamide) achievement of the optimal dose.‍​‍‍‍​‍‍‍‍‍‍‍‍​‍ In a clinical study in patients with polycythaemia vera, individual titration of ropeginterferon alfa-2b took a median of approximately 3.7 months, compared with approximately 2.6 months for hydroxycarbamide. In patients where rapid reduction of blood count values is required to prevent thrombosis and haemorrhage, other medicinal products (e.g. hydroxycarbamide) may be more appropriate. During the titration phase, the medicinal product may not have full efficacy in preventing cardiovascular complications and thromboembolism. Patients should be carefully monitored, particularly during the titration phase. Regular monitoring of complete blood count including haematocrit, leucocyte count and platelet count should be ensured, including after the optimal dose has been achieved. Phlebotomy may need to be performed for rapid reduction of blood viscosity. Endocrine system Pre-existing thyroid disease must be treated and controlled with conventional therapy prior to treatment with ropeginterferon alfa-2b (see section 4.3). In patients who develop symptoms suggestive of thyroid dysfunction during treatment with ropeginterferon alfa-2b, thyroid-stimulating hormone (TSH) levels should be evaluated. If TSH levels can be maintained within the normal range, treatment may continue. Diabetes mellitus has been observed during treatment with other interferon alfa medicinal products (see section 4.8). Treatment with ropeginterferon alfa-2b should not be initiated in patients with diabetes that cannot be effectively controlled with medicinal products. In patients who develop diabetes during treatment that cannot be controlled with medicinal products, treatment with ropeginterferon alfa-2b should be discontinued. Central nervous system (CNS) CNS effects, particularly depression, were observed in some patients treated with ropeginterferon alfa-2b during the clinical development programme (see section 4.8). Other CNS effects, including suicidal ideation, suicide attempt, aggression, bipolar disorder, mania and confusional state, have been observed with other interferon alfa medicinal products. Patients should be carefully monitored for signs of psychiatric disorders, and if such signs appear, the treating physician should consider their management. If psychiatric symptoms worsen, it is recommended to discontinue treatment with ropeginterferon alfa-2b. Ropeginterferon alfa-2b must not be administered to patients with existing severe psychiatric disorders or a history of such disorders, particularly severe depression, suicidal ideation or suicide attempt (see section 4.3). Cardiovascular system Cardiac events including cardiomyopathy, myocardial infarction, atrial fibrillation and coronary artery ischaemic disorders have been associated with interferon alfa treatment (see section 4.8). Patients with pre-existing cardiovascular disorders or a history of such disorders must be carefully monitored during treatment with ropeginterferon alfa-2b. This medicinal product is contraindicated in patients with severe pre-existing cardiovascular disease or in patients who have recently had a cerebrovascular accident or myocardial infarction (see section 4.3). Respiratory system Respiratory disorders such as pulmonary infiltrates, pneumonitis, pneumonia or pulmonary arterial hypertension have been observed in rare cases in patients treated with interferon alfa (see section 4.8). Patients who develop respiratory symptoms should be carefully monitored and treatment with ropeginterferon alfa-2b should be discontinued as appropriate. Vision Severe eye disorders such as retinopathy, retinal haemorrhage, retinal exudates, retinal detachment and retinal artery occlusion or retinal vein occlusion, which may result in blindness, have been reported in rare cases in patients treated with interferon alfa (see section 4.8). Patients should undergo ophthalmological examination before and during treatment with ropeginterferon alfa-2b, particularly patients with conditions associated with retinopathy, such as diabetes mellitus or hypertension. Any patient who reports deterioration of vision or loss of sight or other ocular symptoms must promptly undergo ophthalmological examination. Discontinuation of treatment with ropeginterferon alfa-2b should be considered in patients who develop new or worsening eye disorders. Acute hypersensitivity Serious acute hypersensitivity reactions (e.g. urticaria, angioedema, bronchoconstriction, anaphylaxis) have been observed rarely during treatment with other interferon alfa medicinal products. If such reactions occur, treatment with ropeginterferon alfa-2b must be discontinued and appropriate therapy must be initiated immediately. Transient rashes do not necessitate treatment interruption. Hepatic function Interferon alfa therapy may cause hepatotoxicity, which may manifest as significant elevations in hepatic enzyme levels. Hepatic failure has been reported in patients infected with hepatitis C virus who were treated with other interferon alfa medicinal products (see section 4.8). Elevated ALT (≥ 3 × upper limit of normal), AST (≥ 3 × upper limit of normal), GGT (≥ 3 × upper limit of normal) and bilirubin (> 2 × upper limit of normal) have also been observed in patients treated with ropeginterferon alfa-2b. These were mostly transient and occurred during the first year of treatment. Hepatic disorders have been reported in patients on long-term treatment with ropeginterferon alfa-2b (see section 4.8). Hepatic enzymes and liver function should be regularly monitored in patients on long-term treatment with ropeginterferon alfa-2b. Treatment with ropeginterferon alfa-2b should be discontinued if hepatic enzyme elevations are progressive and clinically significant despite dose reduction. In patients who develop signs of hepatic decompensation during treatment, ropeginterferon alfa-2b should be discontinued. Ropeginterferon alfa-2b is contraindicated in patients with decompensated hepatic cirrhosis (see section 4.3). Renal function Regardless of the starting dose or degree of renal impairment, patients should be monitored. If renal function decreases during treatment, treatment with ropeginterferon alfa-2b should be discontinued. Ropeginterferon alfa-2b is contraindicated in patients with end-stage renal disease (see section 4.3). Dental and periodontal disorders Dental and periodontal disorders, which may lead to tooth loss, have been reported with other interferon alfa medicinal products (see section 4.8). Additionally, dry mouth may have a damaging effect on teeth and oral mucosa during long-term treatment with ropeginterferon alfa-2b. Patients should brush their teeth thoroughly twice daily and attend regular dental examinations. Skin disorders Administration of ropeginterferon alfa-2b is associated with skin disorders (pruritus, alopecia, rash, erythema, psoriasis, xeroderma, acneiform dermatitis, hyperkeratosis, hyperhidrosis). Discontinuation of treatment should be considered if these skin disorders occur or worsen. Excipients Besremi contains benzyl alcohol. Large volumes must be administered with caution and only if necessary, particularly in patients with hepatic or renal impairment, as there is a risk of accumulation and toxic reactions (metabolic acidosis). Besremi contains polysorbate 80. This medicinal product contains 0.025 mg of polysorbate 80 per 0.5 ml. Polysorbates may cause allergic reactions. Besremi contains less than 1 mmol sodium (23 mg) per 1 ml, i.e. it is essentially "sodium-free".