Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2020 Publisher: AbbVie Ltd., Maidenhead, SL6 4UB, UK
Paricalcitol is indicated in adults for the prevention and treatment of secondary hyperparathyroidism in patients with chronic kidney disease Stage 5 who are undergoing haemodialysis.
1) Initial dose should be calculated based on baseline parathyroid hormone (PTH) levels:
The initial dose of paricalcitol is based on the following formula:
Initial dose (micrograms) = baseline intact PTH level in pmol/l / 8
OR = baseline intact PTH level in pg/ml / 80
and administered as an intravenous (IV) bolus dose no more frequently then every other day at any time during dialysis.
The maximum dose safely administered in clinical studies was as high as 40 micrograms.
2) Titration dose:
The currently accepted target range for PTH levels in end-stage renal failure subjects undergoing dialysis is no more than 1.5 to 3 times the non-uremic upper limit of normal, 15.9 to 31.8 pmol/l (150-300 pg/ml), for intact PTH. Close monitoring and individual dose titration are necessary to reach appropriate physiological endpoints. If hypercalcaemia or a persistently elevated corrected Ca x P product greater than 5.2 mmol2/l2 (65 mg2/dl2) is noted, the dosage should be reduced or interrupted until these parameters are normalised. Then, paricalcitol administration should be reinitiated at a lower dose. Doses may need to be decreased as the PTH levels decrease in response to therapy.
The following table is a suggested approach for dose titration:
| Suggested Dosing Guidelines (Dose adjustments at 2 to 4 week intervals) | |
|---|---|
| iPTH Level Relative to Baseline | Paricalcitol Dose Adjustment |
| Same or increased | Increase by 2 to 4 micrograms |
| Decreased by <30% | |
| Decreased by ≥30%, ≤60% | Maintain |
| Decrease by 2 to 4 micrograms | |
| IPTH <15.9 pmol/l (150 pg/ml) | |
Once dosage has been established, serum calcium and phosphate should be measured at least monthly. Serum intact PTH measurements are recommended every three months. During dose adjustment with paricalcitol, laboratory tests may be required more frequently.
Unbound concentrations of paricalcitol in patients with mild to moderate hepatic impairment are similar to healthy subjects and dose adjustment is not necessary in this patient population. There is no experience in patients with severe hepatic impairment.
The safety and efficacy of Zemplar in children have not been established. No data are available on children under 5 years. Currently available data on paediatric patients are described in Section 5.1 but no recommendation on a posology can be made.
There is a limited amount of experience with patients 65 years of age or over receiving paricalcitol in the phase III studies. In these studies, no overall differences in efficacy or safety were observed between patients 65 years or older and younger patients.
Zemplar solution for injection is administered via haemodialysis access.
No case of overdose has been reported.
Overdosage of paricalcitol may lead to hypercalcaemia, hypercalciuria, hyperphosphatemia, and over suppression of PTH (see section 4.4).
In the event of an overdose, signs and symptoms of hypercalcaemia (serum calcium levels) should be monitored and reported to a physician. Treatment should be initiated as appropriate.
Paricalcitol is not significantly removed by dialysis. Treatment of patients with clinically significant hypercalcaemia consists of immediate dose reduction or interruption of paricalcitol therapy and includes a low calcium diet, withdrawal of calcium supplements, patient mobilisation, attention to fluid and electrolyte imbalances, assessment of electrocardiographic abnormalities (critical in patients receiving digitalis), and haemodialysis or peritoneal dialysis against a calcium-free dialysate, as warranted.
When serum calcium levels have returned to within normal limits, paricalcitol may be reinitiated at a lower dose. If persistent and markedly elevated serum calcium levels occur, there are a variety of therapeutic alternatives that may be considered. These include the use of drugs such as phosphates and corticosteroids as well as measures to induce diuresis.
Zemplar solution for injection contains 30% v/v of propylene glycol as an excipient. Isolated cases of Central Nervous System depression, haemolysis and lactic acidosis have been reported as toxic effect associated with propylene glycol administration at high doses. Although they are not expected to be found with Zemplar administration as propylene glycol is eliminated during the dialysis process, the risk of toxic effect in overdosing situations has to be taken into account.
Vial: 3 years.
Ampoule: 2 years.
After opening, use immediately.
This medicinal product does not require any special storage conditions.
Each Type 1 glass ampoule contains 1ml or 2ml of solution for injection.
Each Type 1 glass vial contains 1ml or 2ml of solution for injection.
The presentations of Zemplar are:
Pack containing 5 ampoules of 1ml of solution for injection.
Pack containing 5 ampoules of 2ml of solution for injection.
Pack containing 5 vials of 1ml of solution for injection.
Pack containing 5 vials of 2ml of solution for injection.
Not all pack sizes may be marketed.
Parenteral medicinal products should be inspected visually for particulate matter and discoloration prior to administration. The solution is clear and colourless.
For single use only.
Any unused medicinal product or waste should be disposed of in accordance with local requirements.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
