Posology : מינונים

4.2      Posology and method of administration

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


Baseline iPTH Level                   Daily Dose                 Three Times a Week Dose* ≤ 500 pg/ml (56 pmol/l)               1 microgram                       2 micrograms > 500 pg/ml (56 pmol/l)               2 micrograms                      4 micrograms *
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

Dose Adjustment at 2 to 4 Week Intervals iPTH Level Relative to Baseline
Daily Dose         Three Times a Week Dose1
The same or increased           Increase              Increase
Decreased by < 30%              1 microgram           2 micrograms
Decreased by ≥30%, ≤60%         Maintain              Maintain
Decreased > 60%                 Decrease2             Decrease2 iPTH < 60 pg/ml (7 pmol/l)      1 microgram           2 micrograms
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
OR

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

Zemplar is not indicated for children and adolescents below 18 years of age.
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.