Cinacalcet hydrochloride

Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Sensipar (Amgen)
30 mg, 60 mg and 90 mg tablets
Approved indications: hyperparathyroidism, hypercalcaemia
Australian Medicines Handbook section 10.3

Parathyroid hormone increases calcium concentrations by increasing bone resorption and the reabsorption of calcium by the kidney. Adenomas of the parathyroid glands cause primary hyperparathyroidism and parathyroidectomy may be indicated. Secondary hyperparathyroidism is a reaction to hypocalcaemia which can have a variety of causes such as renal failure or vitamin D deficiency.

The secretion of parathyroid hormone depends on a receptor which senses the serum calcium concentration. By increasing the sensitivity of this receptor to calcium, treatment with cinacalcet reduces the secretion of parathyroid hormone which in turn reduces the calcium concentration.

Cinacalcet tablets have a bioavailability of 20-25%, but this increases if they are taken with food. Peak plasma concentrations are achieved 2-6 hours after a dose and this corresponds with the nadir of parathyroid hormone secretion. This suppression lasts long enough to allow once-daily dosing for secondary hyperparathyroidism. Cinacalcet is cleared by metabolism which includes cytochrome P450 3A4, 2D6 and 1A2. This results in interactions with drugs such as ketoconazole and rifampicin. Smoking increases clearance by inducing P450 1A2.

Several small studies have investigated cinacalcet in patients with primary hyperparathyroidism or parathyroid carcinoma. A short dose-ranging study found that cinacalcet significantly decreased the serum calcium concentration. In one study, a twice-daily dose of 30 mg reduced the concentration by 11% and 50 mg twice daily reduced it by 18.5%. At its nadir the concentration of parathyroid hormone fell by half.¹ Doses should be titrated according to the hormone or calcium concentration.

More data are available on the use of cinacalcet to treat secondary hyperparathyroidism in patients having renal dialysis. In a 26-week study, 741 patients were randomised to receive once-daily cinacalcet or placebo. Mean concentrations of parathyroid hormone were reduced by 43% in the cinacalcet group, but increased by 9% in the placebo group. However, only 43% of the patients taking cinacalcet reached the target concentration of parathyroid hormone.²

Nausea and vomiting are the most frequent adverse reactions to cinacalcet. Less common adverse events are hypocalcaemia, convulsions and paraesthesia.

The studies of cinacalcet have focussed on biochemical tests. There is little information on clinically important outcomes, particularly in primary hyperparathyroidism. Although cinacalcet may be useful in treating the hypercalcaemia associated with parathyroid carcinoma, its approval in primary hyperparathyroidism is restricted to patients who cannot have a parathyroidectomy. While cinacalcet is efficacious in reducing parathyroid hormone concentrations in secondary hyperparathyroidism in patients having renal dialysis, longer-term studies will be needed to assess its effect on bone and the vascular system.