Duzallo

Posology Dose titration with allopurinol to an adequate dose must be done before the patient is switched to Duzallo. The choice of the dose strength of Duzallo depends on the allopurinol dose taken as individual tablet(s). The recommended dose is one tablet of Duzallo (200 mg/200 mg or 300 mg/200 mg) once daily.

4). Patients who are currently treated with allopurinol doses higher than 300 mg can be switched to Duzallo 200 mg/200 mg or Duzallo 300 mg/200 mg and should receive complementary doses of allopurinol to cover the total dose of allopurinol taken before switching to Duzallo.

Patients should be instructed to stay well hydrated. 4). The target serum uric acid level is less than 6 mg/dL (360 μmol/L). In patients with tophi or persistent symptoms, the target is less than 5 mg/dL (300 μmol/L). 4). 2); however, elderly patients are more likely to have decreased renal function (see dosing recommendations for renal impairment).

Experience in very elderly patients (≥75 years) is limited. 4). 1). Duzallo should be used with caution in patients with a CrCL of 30 to less than 45 mL/min (expe- rience with lesinurad in patients with an estimated CrCL (eCrCL) less than 45 mL/min is limited).

2). Duzallo has not been studied in patients with severe hepatic impairment; therefore, no dose recommendations can be given for Duzallo. Paediatric population The safety and efficacy of Duzallo in children and adolescents under 18 years of age have not yet been established.

No data are available. Method of administration Oral use. Medicinal product no longer authorised 4

Summary of the safety profile The safety of lesinurad 200 mg was evaluated in the Phase 3 combination therapy clinical trials (including extension studies). The most commonly reported adverse reactions during treatment with lesinurad 200 mg are influenza, gastro-oesophageal reflux disease, headache and blood creatinine increased.

The serious adverse reactions renal failure, renal impairment and nephrolithiasis have occurred uncommonly (less than 1 case per 100 patients) (see Table 1). In clinical trials, most adverse reactions were mild or moderate in intensity and resolved while continuing lesinurad therapy.

8%). For allopurinol, undesirable effects may vary in their incidence depending on the dose received and also when given in combination with other medicinal products. Tabulated list of adverse reactions Adverse reactions are classified according to frequency and System Organ Class.

Frequency categories are defined according to the following conventions: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10000 to <1/1000) and very rare (<1/10,000). Table 1 lists adverse reactions identified in clinical studies with patients receiving lesinurad 200 mg once daily in combination with allopurinol and those adverse reaction that are established for allopurinol alone.

Table 1 Adverse reactions by System Organ Class and frequency System Organ Classification Common Uncommon Rare Very Rare Infections and infestations Influenza Furuncle Neoplasms benign, malignant and unspecified (incl cysts and polyps) Angioimmunoblastic T-cell lymphoma Blood and lymphatic system disorders Agranulocytosis*, aplastic anaemia*, thrombocytopenia* Immune system disorders Hypersensitivity* * Metabolism and nutrition disorders Dehydration Diabetes mellitus, hyperlipidaemia Psychiatric disorders DepressionMedicinal product no longer authorised 10 System Organ Classification Common Uncommon Rare Very Rare Nervous system disorders Headache Coma, paralysis, ataxia, neuropathy, paraesthesia, drowsiness/somnolence, dysgeusia Eye disorders Cataract, vision disorders (visual impairment and blurred vision), maculopathy Ear and labyrinth disorders Vertigo Cardiac disorders Angina pectoris, bradycardia Vascular disorders Hypertension Gastrointestinal disorders Gastro- oesophageal reflux disease Nausea, vomiting and diarrhoea Recurrent haematemesis, steatorrhoea, stomatitis, changed stool frequency Hepatobiliary disorders Impaired liver function tests Hepatitis Skin and subcutaneous tissue disorders Rash Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, medicinal product eruption, alopecia, hair colour changes Musculoskeletal and connective tissue disorders Myalgia Renal and urinary disorders Renal failure***, renal impairment, nephrolithiasis Urolithiasis Haematuria, azotemia Reproductive system and breast disorders Male infertility, erectile dysfunction, gynaecomastia General disorders and administration site conditions Oedema, general malaise, asthaeniaMedicinal product no longer authorised 11 System Organ Classification Common Uncommon Rare Very Rare Investigations Blood thyroid stimulating hormone increased****, blood creatinine increased * Very rare reports have been received of thrombocytopenia, agranulocytosis and aplastic anaemia, particularly in individuals with impaired renal and/or hepatic function ** Photodermatosis, photosensitivity reaction, dermatitis allergic, pruritus and urticaria.

Pre-existing cardiovascular disease Duzallo is not recommended in patients with unstable angina, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled hypertension or with a recent event of myocardial infarction, stroke, or deep venous thrombosis within the last 12 months, due to insufficient data with lesinurad.

8). Renal events Treatment with lesinurad 200 mg in combination with allopurinol was associated with an increased incidence of serum creatinine elevations, which are related to increased renal uric acid excretion. 8) Renal function should be evaluated prior to initiation of Duzallo and monitored periodically thereafter (e.

g. 4 times per year), based on clinical considerations, such as baseline renal function, volume depletion, concurrent illness or concomitant medicinal products. 5 times the pre-treatment value should be closely monitored. 0 mg/dL. Treatment should be interrupted in patients who report symptoms that may indicate acute uric acid nephropathy, including flank pain, nausea or vomiting, and measure serum creatinine promptly.

Duzallo should not be restarted without another explanation for the serum creatinine abnormalities. 2). Hypersensitivity syndrome, Stevens-Johnson-Syndrome (SJS ) and toxic epidermal necrolysis (TEN) Allopurinol hypersensitivity reactions can manifest in many different ways, including maculopapular exanthema, hypersensitivity syndrome (also known as DRESS) and SJS/TEN.

Re-challenge should not be undertaken in patients with hypersensitivity syndrome and SJS/TEN. Corticosteroids may be beneficial in overcoming hypersensitivity skin reactions. Duzallo and all additional doses of allopurinol should be discontinued immediately at the first appearance of allopurinol-induced skin rash or other signs which may indicate an allergic reaction and additional medical care should be provided as needed.

Medicinal product no longer authorised 5 HLA-B*5801 allele The HLA-B*5801 allele has been shown to be associated with the risk of developing allopurinol related hypersensitivity syndrome and SJS/TEN. The frequency of the HLA-B*5801 allele varies widely between ethnic populations: up to 20% in Han Chinese population, 8-15% in the Thai, about 12% in the Korean population and 1-2% in individuals of Japanese or European origin.

1. Tumour lysis syndrome or Lesch-Nyhan syndrome. 2).