ZEMPLAR Capsule, soft Ref.[8396] Active ingredients: Paricalcitol

Posology

Chronic Kidney Disease (CKD) Stages 3 and 4

Zemplar should be administered once a day, either daily or three times a week taken every other day.

Initial dose

The initial dose is based on baseline intact parathyroid hormone (iPTH) levels.

Table 1. Initial Dose:

* To be administered no more frequently than every other day

Dose titration

Dosing must be individualised based on serum or plasma iPTH levels, with monitoring of serum calcium and serum phosphorus. Table 2 presents a suggested approach for dose titration.

Table 2. Dose Titration:

¹ To be administered no more frequently than every other day.
² If a patient is taking the lowest dose on the daily or three times a week regimen, and a dose reduction is needed, dosing frequency can be decreased.

Serum calcium levels should be closely monitored after initiation of the treatment and during dose titration periods. If hypercalcaemia or a persistently elevated calcium-phosphate product greater than 55 mg²/dl² (4.4 mmol²/l²) is observed, the dose of calcium based phosphate binders should be reduced or withheld. Alternatively, the dose of Zemplar may be reduced or temporarily interrupted. If interrupted, the drug should be restarted at a lower dose, when serum calcium and calcium-phosphate product are in the target range.

Chronic Kidney Disease (CKD), Stage 5

Zemplar should be administered three times a week every other day.

Initial dose

The initial dose of Zemplar in micrograms is based on a baseline iPTH level (pg/ml)/60 [(pmol/l)/7], up to an initial maximum dose of 32 micrograms.

Dose titration

Subsequent dosing should be individualised and based on iPTH, serum calcium and phosphorus levels. A suggested dose titration of paricalcitol capsules is based on the following formula:

Titration dose (micrograms) = most recent iPTH level (pg/ml) / 60

Titration dose (micrograms) = most recent iPTH level (pmol/l) / 7

Serum calcium and phosphorus levels should be closely monitored after initiation, during dose titration periods, and with co-administration of strong P450 3A inhibitors. If an elevated serum calcium or elevated Ca x P is observed and the patient is on a calcium-based phosphate binder, the binder dose may be decreased or withheld, or the patient may be switched to a non-calcium-based phosphate binder.

If serum calcium >11.0 mg/dl (2.8 mmol/l) or Ca x P >70 mg²/dl² (5.6 mmol²/l²) or iPTH ≤150 pg/ml, the dose should be decreased by 2 to 4 micrograms with respect to that calculated by the most recent iPTH/60 (pg/ml) [iPTH/7 (pmol/l)]. If further adjustment is required, the dose of paricalcitol capsules should be reduced or interrupted until these parameters are normalised.

As iPTH approaches the target range (150-300 pg/ml), small, individualised dose adjustments may be necessary in order to achieve a stable iPTH. In situations where monitoring of iPTH, Ca or P occurs less frequently than once per week, a more modest initial and dose titration ratio may be warranted.

Special populations

Hepatic impairment

No dose adjustment is required in patients with mild to moderate hepatic impairment.

There is no experience in patients with severe hepatic impairment (see section 5.2).

Renal transplant

Post-renal transplant patients with CKD Stages 3 and 4 and secondary hyperparathyroidism were not studied in phase 3 clinical trials. Based on the published literature, the initial dose and dose-titration algorithm for patients with post-transplant CKD Stages 3 and 4 and secondary hyperparathyroidism is the same as for patients with native CKD Stages 3 and 4 and secondary hyperparathyroidism. Serum calcium and phosphorus levels should be closely monitored after initiation, during dose titration periods, and with co-administration of strong cytochrome P450 3A inhibitors.

Paediatric population

The safety and efficacy of Zemplar capsules in children under the age of 10 years have not yet been established.

CKD Stages 3 and 4 (Ages 10 to 16 years old):

Initial dose:

The recommended starting dose of paricalcitol capsules is 1 microgram administered three times a week, no more frequently than every other day.

Dose titration:

Subsequent dosing should be individualized and based on iPTH, serum calcium and phosphorus levels to maintain an iPTH level between 35 and 69 pg/ml (Stage 3) or 70 and 110 pg/ml (Stage 4).

Paricalcitol dose may be increased in 1 microgram increments every 4 weeks, maintaining the three times per week regimen. At any time, the dose may be decreased by 1 microgram or may be held if the patient is receiving a 1 microgram dose. Paricalcitol may be stopped if the patient requires reduction while receiving 1 microgram three times per week, resuming when appropriate. The maximum dose administered in the clinical study was 7 micrograms per dose.

CKD Stage 5:

The efficacy of Zemplar in children with CKD Stage 5 has not been established.

Elderly

No overall differences in safety and effectiveness were observed between elderly patients (65–75 years) with regard to younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Method of administration

Zemplar can be taken with or without food.

Excessive administration of Zemplar capsules can cause hypercalcaemia, hypercalciuria, hyperphosphataemia, and over suppression of parathyroid hormone. High intake of calcium and phosphate concomitant with Zemplar capsules may lead to similar abnormalities.

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.

Signs and symptoms of vitamin D intoxication associated with hypercalcaemia include:

Early: Weakness, headache, somnolence, nausea, vomiting, dry mouth, constipation, muscle pain, bone pain and metallic taste.

Late: Anorexia, weight loss, conjunctivitis (calcific), pancreatitis, photophobia, rhinorrhoea, pruritus, hyperthermia, decreased libido, elevated BUN, hypercholesterolaemia, elevated AST and ALT, ectopic calcification, hypertension, cardiac arrhythmias, somnolence, death and rarely, overt psychosis.

Serum calcium levels should be monitored frequently until normocalcaemia ensues.

Paricalcitol is not significantly removed by dialysis.

2 years.

This medicinal product does not require any special storage conditions.

High-density polyethylene (HDPE) bottles closed with child resistant polypropylene caps. Each bottle contains 30 capsules.

PVC/fluoropolymer/aluminium blister strips containing 7 capsules. Each carton contains 1 or 4 blister strips. Packaged in outer cartons containing either 7 or 28 capsules.

Not all pack sizes may be marketed.

No special requirements.