Trade names Zemplar MedlinePlus a682335 ATC code H05BX02 (WHO) | AHFS/Drugs.com Monograph Routes ofadministration Oral, Intravenous | |
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Pregnancycategory AU: CUS: C (Risk not ruled out) | ||
Paricalcitol (chemically it is 19-nor-1,25-(OH)2-vitamin D2. Marketed by Abbott Laboratories under the trade name Zemplar) is a drug used for the prevention and treatment of secondary hyperparathyroidism (excessive secretion of parathyroid hormone) associated with chronic renal failure. It is an analog of 1,25-dihydroxyergocalciferol, the active form of vitamin D2 (ergocalciferol).
Contents
Medical uses
Its primary use in medicine is in the treatment of secondary hyperparathyroidism associated with chronic kidney disease. In three placebo-controlled studies, chronic renal failure patients treated with paricalcitol achieved a mean parathyroid hormone (PTH) reduction of 30% in six weeks. Additionally there was no difference in incidence of hypercalcemia or hyperphosphatemia when compared to placebo. A double-blind randomised study with 263 dialysis patients showed a significant advantage over calcitriol (also known as activated vitamin D3; a similar molecule to 1,25-dihydroxyergocalciferol, adding a methyl group on C24 and lacking a double-bond in the C22 position). After 18 weeks, all patients in the paricalcitol group had reached the target parathormone level of 100 to 300 pg/ml, versus none in the calcitriol group. Combination therapy with paricalcitol and trandolapril has been found to reduce fibrosis in obstructive uropathy. Forty-eight week therapy with paricalcitol did not alter left ventricular mass index or improve certain measures of diastolic dysfunction in 227 patients with chronic kidney disease.
Adverse effects
Adverse effects by frequency:
Very common (>10% frequency):
Common (1-10% frequency):
Uncommon (0.1-1% frequency):
‡ These are adverse effects only seen in patients with grade 3 or 4 chronic kidney disease. † These are adverse effects only seen in patients with grade 5 chronic kidney disease.
Contraindications
Contraindications include:
whereas cautions include:
Interactions
Drugs that may interact with paricalcitol include:
Overdose
Electrolyte abnormalities (e.g. hypercalcaemia and hyperphosphataemia) are common overdose symptoms. Treatment is mostly supportive, with particular attention being paid to correcting electrolyte anomalies and reducing intake of calcium in both the form of supplementation and diet. As it is so heavily bound to plasma proteins haemodialysis is unlikely to be helpful in cases of overdose.
Early symptoms of overdose can include:
It is worth noting, however, that may of these symptoms are also indicative of kidney failure and hence may be masked by the patient's condition.
Late symptoms of overdose include:
Mechanism of action
Like 1,25-dihydroxyergocalciferol, paricalcitol acts as an agonist at the vitamin D receptor and thereby lowers parathyroid hormone levels in the blood.
Pharmacokinetics
The plasma concentration of paricalcitol decreases rapidly and log-linearly within two hours after initial intravenous administration. Therefore, it is not expected to accumulate with multiple dosing, since paricalcitol is usually given no more frequently than every other day (3 times per week).