CINACALCET

Posology 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. If serum calcium levels decrease below the normal range, appropriate steps should be taken, including adjustment of concomitant therapy.

4). 4). Parathyroid carcinoma and primary hyperparathyroidism Adults and elderly (> 65 years) The recommended starting dose of Cinacalcet for adults is 30 mg twice per day. The dose of Cinacalcet should be titrated every 2 to 4 weeks through sequential doses of 30 mg twice daily, 60 mg twice daily, 90 mg twice daily, and 90 mg three or four times daily as necessary to reduce serum calcium concentration to or below the upper limit of normal.

The maximum dose used in clinical trials was 90 mg four times daily. Serum calcium should be measured within 1 week after initiation or dose adjustment of Cinacalcet. Once maintenance dose levels have been established, serum calcium should be measured every 2 to 3 months.

1). Switch from etelcalcetide to Cinacalcet The switch from etelcalcetide to Cinacalcet and the appropriate wash out period has not been studied in patients. In patients who have discontinued etelcalcetide, Cinacalcet should not be initiated until at least three subsequent haemodialysis sessions have been completed, at which time serum calcium should be measured.

8). 4). Hepatic impairment No change in starting dose is necessary. 2). Method of administration For oral use. 2). Tablets should be taken whole and should not be chewed, crushed or divided.

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 “Description of selected adverse reactions” 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). d) Paediatric population Cinacalcet is not indicated for use in paediatric patients. The safety and efficacy of Cinacalcet in the paediatric population have not been established. 4). 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. 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 Cinacalet 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). CKD patients not on dialysis Cinacalcet is not indicated for CKD patients not on dialysis. 1 mmol/L]) compared with cinacalcet-treated CKD patients on dialysis, which may be due to lower baseline calcium levels and/or the presence of residual kidney function.

8). The threshold for seizures is lowered by significant reductions in serum calcium levels. Therefore, serum calcium levels should be closely monitored in patients receiving Cinacalcet, particularly in patients with a history of a seizure disorder.

1. 4).