2.1 Chronic Kidney Disease Stages 3 and 4 in Adults

Administer ZEMPLAR capsules orally once daily or three times a week [see Clinical Studies (14.1)]. When dosing three times weekly, do not administer more frequently than every other day.

Initial Dose

Table 1. Recommended ZEMPLAR Starting Dose Based upon Baseline iPTH Level

Dose Titration

Table 2. Recommended ZEMPLAR Dose Titration Base upon iPTH Level

If a patient is taking the lowest dose, 1 mcg, on the daily regimen and a dose reduction is needed, the dose can be decreased to 1 mcg three times a week. If a further dose reduction is required, the drug should be withheld as needed and restarted at a lower dosing frequency.

2.2 Chronic Kidney Disease Stage 5 in Adults

Initial Dose

Administer the dose of ZEMPLAR capsules orally three times a week, no more frequently than every other day based upon the following formula:

Dose (micrograms) = baseline iPTH (pg/mL) divided by 80

Treat patients only after their baseline serum calcium has been adjusted to 9.5 mg/dL or lower to minimize the risk of hypercalcemia [see Clinical Pharmacology (12.2) and Clinical Studies (14.2)].

Dose Titration

Individualize the dose of ZEMPLAR based on iPTH, serum calcium and phosphorus levels. Titrate ZEMPLAR dose based on the following formula:

Dose (micrograms) = most recent iPTH level (pg/ml) divided by 80

If serum calcium is elevated, the dose should be decreased by 2 to 4 micrograms.

As iPTH approaches the target range, small, individualized 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 (e.g., iPTH divided by 100) may be warranted.

2.3 Pediatric Patients (Ages 10 to 16 Years)

CKD Stages 3 and 4

Initial Dose

Administer ZEMPLAR 1 mcg capsule orally three times a week, no more frequently than every other day.

Dose Titration

Individualize and titrate ZEMPLAR dose based on iPTH, serum calcium and phosphorus levels to maintain an iPTH level within target range.

Every 4 weeks, each administered ZEMPLAR dose may be increased in 1 mcg increments, maintaining the three times per week regimen (e.g., increase from 1 mcg three times per week to 2 mcg three times per week). At any time, each administered dose may be decreased by 1 mcg. ZEMPLAR may be stopped if the patient requires reduction while receiving 1 mcg three times per week, resuming when appropriate.

CKD Stage 5

Initial Dose

Administer the dose of ZEMPLAR capsules orally three times a week, no more frequently than every other day based upon the following formula:

Dose* (micrograms) = baseline iPTH (pg/mL) divided by 120

* Round down to the nearest whole number

Dose Titration

Subsequent dosing should be individualized and based on iPTH, serum calcium and phosphorus levels to maintain an iPTH level within target range.

Every 4 weeks, each administered ZEMPLAR dose may be increased in 1 mcg increments, maintaining the three times per week regimen (e.g., increase from 1 mcg three times per week to 2 mcg three times per week). At any time, each administered dose may be decreased by 2 mcg. ZEMPLAR may be stopped if the patient requires reduction while receiving 2 mcg three times per week or 1 mcg three times per week, resuming when appropriate.

2.4 Monitoring

Monitor serum calcium and phosphorus levels closely after initiation of ZEMPLAR, during dose titration periods and during co-administration with strong CYP3A inhibitors [see Warnings and Precautions (5.3), Drug Interactions (7), and Clinical Pharmacology (12.3)].

If hypercalcemia is observed, the dose of ZEMPLAR should be reduced or withheld until these parameters are normalized.

2.5 Administration

ZEMPLAR capsules may be taken without regard to food.