ZEMPLAR

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 Decreased by < 30% Increase 1 microgram Increase 2 micrograms Decreased by ≥30%, ≤60% Maintain Maintain Decreased > 60% iPTH < 60 pg/ml (7 pmol/l) Decrease2 1 microgram Decrease2 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.

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.

Summary of the safety profile The safety of paricalcitol capsules has been evaluated in three 24-week, double-blind, placebo-controlled, multi-centre clinical trials involving 220 CKD Stage 3 and 4 adult patients and in one 12-week, double-blind, placebo-controlled, multi-centre clinical trial involving 88 CKD Stage 5 adult patients.

In addition, there is postmarketing experience with paricalcitol capsules from three additional studies, and paediatric experience from two studies. The most commonly reported adverse reactions for paricalcitol treated patients were hypercalcaemia and calcium phosphate product increased.

In the Stage 3/4 and Stage 5 clinical trials, the incidence of hypercalcaemia was Zemplar (3/167, 2%) vs placebo (0/137, 0%) and elevated calcium phosphate product was Zemplar (19/167, 11%) vs placebo (8/137, 6%). Tabulated list of adverse reactions All adverse reactions associated with Zemplar capsules are displayed in Table 3 by MedDRA System Organ Class, Preferred Term and frequency.

The following frequency groupings are used: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).

4). Paediatric population In children 10 years of age and older, the nature of the safety profile is similar to that seen in adults. Adverse reactions for paricalcitol treated patients were hypercalcaemia (4/47, 9%), hyperphosphataemia (2/47, 4%), headache (1/47, 2%), and nausea (1/47, 2%).

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Over suppression of parathyroid hormone may result in elevations of serum calcium levels and may lead to low-turnover bone disease. Patient monitoring and individualised dose titration is required to reach appropriate physiological endpoints.

If clinically significant hypercalcaemia develops and the patient is receiving a calcium-based phosphate binder, the dose of the calcium-based phosphate binder should be reduced or interrupted. Chronic hypercalcaemia may be associated with generalized vascular calcification and other soft-tissue calcification.

5). 5). In pre-dialysis patients, paricalcitol, like other vitamin D receptor activators, may increase serum creatinine (and therefore decrease the estimated GFR [eGFR]) without changing true glomerular filtration rate (GFR). 5). 42 mg of alcohol (ethanol).

The amount per capsule of this medicine is equivalent to less than 1 ml beer or wine.

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