New drug
Paricalcitol
- Aust Prescr 2008;31:108-11
- 1 August 2008
- DOI: 10.18773/austprescr.2008.062
ISSUE 4 AUGUST
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.
Zemplar (Abbott)
1 microgram, 2 microgram and 4 microgram capsules
5 microgram/mL in 1 mL and 2 mL ampoules
Approved indication: secondary hyperparathyroidism
Australian Medicines Handbook section 10.3.2
In chronic renal failure there is reduced production of calcitriol, the active form of vitamin D. This affects calcium homeostasis and leads to increased secretion of parathyroid hormone. High concentrations of parathyroid hormone increase bone resorption leading to renal osteodystrophy. Secondary hyperparathyroidism can be treated with calcitriol, but it may cause hypercalcaemia and hyperphosphataemia. This has led to research into vitamin D analogues, such as paricalcitol.
The dose and frequency of paricalcitol are determined by the patient's concentrations of parathyroid hormone, calcium and phosphorus. The oral formulation is well absorbed whether or not it is taken with food. Paricalcitol is extensively metabolised by several enzymes including cytochrome P450 3A4. Most of the metabolites are excreted in the faeces. In healthy people the half-life of paricalcitol is 4-7 hours, but this increases to 14-20 hours in patients with chronic kidney disease. Haemodialysis has little effect on the elimination of paricalcitol.
Three placebo-controlled trials enrolled a total of 220 patients with secondary hyperparathyroidism due to chronic kidney disease. In one study patients took capsules once a day, in the others patients took them three times a week. The treatment period was 24 weeks and 83% of patients took the drug for at least 16 weeks. The trial end point (two consecutive decreases in parathyroid hormone greater than 30% of the baseline concentration) was achieved by 91% of the patients randomised to paricalcitol compared with 13% of the placebo group. Only two patients given paricalcitol developed hypercalcaemia.1
An open-label study has followed 164 patients, with end-stage renal failure, for up to 13 months. Intravenous doses of paricalcitol given two or three times a week at the end of haemodialysis decreased the concentrations of parathyroid hormone. Mean concentrations of calcium and phosphorus were controlled, but hypercalcaemia occurred in 10% of the patients. Drug-related adverse events affected 26% of patients and 9% withdrew from the study because of adverse events.2
Adverse events which occur more frequently with paricalcitol than with placebo include fever, chills, sepsis, pneumonia, oedema, nausea and vomiting. Patients require regular monitoring for hypercalcaemia.
Although the main trials of paricalcitol gave several doses a week this may not be essential. A small study has found that a weekly intravenous dose may be effective in reducing concentrations of parathyroid hormone.3
The advantages of paricalcitol over calcitriol, seen in an historical study, need confirmation. In approximately 67 000 patients having haemodialysis the mortality rate was 0.223 per person-year in patients receiving calcitriol and 0.18 per person-year in patients receiving paricalcitol.4
manufacturer provided the product information
The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.
References
- Coyne D, Acharya M, Qiu P, Abboud H, Batlle D, Rosansky S, et al. Paricalcitol capsule for the treatment of secondary hyperparathyroidism in stages 3 and 4 CKD. Am J Kidney Dis 2005;47:263-76.
- Lindberg J, Martin KJ, Gonzalez EA, Acchiardo SR, Valdin JR, Soltanek C. A long-term, multi center study of the efficacy and safety of paricalcitol in end-stage renal disease. Clin Nephrol 2001;56:315-23.
- Staniforth ME, Cheng SC, Coyne DW. Once-weekly intravenous paricalcitol in the treatment of secondary hyperparathyroidism in hemodialysis patients. Clin Nephrol 2005;63:454-60.
- Teng M, Wolf M, Lowrie E, Ofsthun N, Lazarus M, Thadhani R. Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med 2003;349:446-56.
