Posology : מינונים

4.2      Posology and method of administration

Posology

Adults
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
Decreased > 60%
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.

Hepatic impairment
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.

Paediatric population (0-18 years)
The safety and efficacy of Rextol 5 mcg/ml in children have not been established.

Elderly (>65years)
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.

Method of administration
Rextol 5mcg/ml Solution for Injection is administered via haemodialysis access.