CINACALCET ACCORDPHARMA

Secondary hyperparathyroidism Adults and elderly (> 65 years) The recommended starting dose for adults is 30 mg once per day. 8 pmol/L) in the intact PTH (iPTH) assay. PTH levels should be assessed at least 12 hours after dosing with cinacalcet.

Reference should be made to current treatment guidelines. PTH should be measured 1 to 4 weeks after initiation or dose adjustment of cinacalcet. PTH should be monitored approximately every 1-3 months during maintenance. Either the intact PTH (iPTH) or bio-intact PTH (biPTH) may be used to measure PTH levels; treatment with cinacalcet does not alter the relationship between iPTH and biPTH.

4). The normal calcium range may differ depending on the methods used by your local laboratory. During dose titration, serum calcium levels should be monitored frequently, and within 1 week of initiation or dose adjustment of cinacalcet.

Once the maintenance dose has been established, serum calcium should be measured approximately monthly. 9 mmol/L), or in the presence of clinical symptoms of hypocalcaemia Calcium-containing phosphate binders, vitamin D sterols and/or adjustment of dialysis fluid calcium concentrations can be used to raise serum calcium according to clinical judgment.

9 mmol/L) or persistent symptoms of hypocalcaemia despite attempts to increase serum calcium Reduce or withhold dose of cinacalcet. 0 mmol/L) and/or symptoms of hypocalcaemia have resolved. Treatment should be reinitiated using the next lowest dose of cinacalcet.

4). The normal calcium range differs depending on the methods used by your local laboratory and the age of the child/patient. 20 mg/kg once daily based on the patient’s dry weight (see table 1). The dose can be increased to achieve a desired target iPTH range.

The dose should be increased sequentially through available dose levels (see table 1) no more frequently than every 4 weeks. 5 mg/kg/day, not to exceed a total daily dose of 180 mg. Table 1. 5, 10, 15, and 30 ≥ 25 to < 36 5, 10, 15, 30, and 60 ≥ 36 to < 50 5 5, 10, 15, 30, 60, and 90 ≥ 50 to < 75 10 10, 15, 30, 60, 90, and 120 ≥ 75 15 15, 30, 60, 90, 120, and 180 Cinacalcet Accordpharma is only available as film-coated tablet.

Thus, it is not possible to administer cinacalcet Accordpharma to paediatric patients that require less than a full 30 mg dose. If an alternate dose is required, other cinacalcet products offering such an option should be used. Dose adjustment based on PTH levels PTH levels should be assessed at least 12 hours after dosing with cinacalcet and iPTH should be measured 1 to 4 weeks after initiation or dose adjustment of cinacalcet.

a) Summary of the safety profile Secondary hyperparathyroidism, parathyroid carcinoma and primary hyperparathyroidism Based on available data from patients receiving cinacalcet in placebo-controlled studies and single-arm studies the most commonly reported adverse reactions were nausea and vomiting.

Nausea and vomiting were mild to moderate in severity and transient in nature in the majority of patients. Discontinuation of therapy as a result of undesirable effects was mainly due to nausea and vomiting. b) Tabulated list of adverse reactions Adverse reactions, considered at least possibly attributable to cinacalcet treatment in the placebo-controlled studies and single-arm studies based on best-evidence assessment of causality are listed below using the following convention: 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).

4 *see section c c) Description of selected adverse reactions Hypersensitivity reactions Hypersensitivity reactions including angioedema and urticaria have been identified during post-marketing use of cinacalcet. The frequencies of the individual preferred terms including angioedema and urticaria cannot be estimated from available data.

Hypotension and/or worsening heart failure There have been reports of idiosyncratic cases of hypotension and/or worsening heart failure in cinacalcet-treated patients with impaired cardiac function in post-marketing safety surveillance, the frequencies of which cannot be estimated from available data.

4). 1). 5 per 100 subject years) had at least one adverse event of hypocalcaemia. 4). Cinacalcet should be used in paediatric patients only if the potential benefit justifies the potential risk. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

Serum calcium Life threatening events and fatal outcomes associated with hypocalcaemia have been reported in adult and paediatric patients treated with cinacalcet. Manifestations of hypocalcaemia may include paraesthesias, myalgias, cramping, tetany and convulsions.

Decreases in serum calcium can also prolong the QT interval, potentially resulting in ventricular arrhythmia secondary to hypocalcaemia. 8). Caution is advised in patients with other risk factors for QT prolongation such as patients with known congenital long QT syndrome or patients receiving medicinal products known to cause QT prolongation.

2). Serum calcium should be measured within 1 week after initiation or dose adjustment of cinacalcet. Adults Cinacalcet treatment should not be initiated in patients with a serum calcium (corrected for albumin) below the lower limit of the normal range.

9 mmol/L). Paediatric population Cinacalcet should only be initiated for the treatment of secondary HPT in children ≥ 3 years old with ESRD on maintenance dialysis therapy, in whom secondary HPT is not adequately controlled with standard of care therapy, where serum calcium is in the upper range of, or above, the age-specified reference interval.

2) and patient compliance during treatment with cinacalcet. Do not initiate cinacalcet or increase the dose if non- compliance is suspected. Prior to initiating cinacalcet and during treatment, consider the risks and benefits of treatment and the ability of the patient to comply with the recommendations to monitor and manage the risk of hypocalcaemia.

Inform paediatric patients and/or their caregivers about the symptoms of hypocalcaemia and about the importance of adherence to instructions about serum calcium monitoring, and posology and method of administration. CKD patients not on dialysis Cinacalcet is not indicated for CKD patients not on dialysis.

1. 4).