Zemplar

(Paricalcitol)
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Dosage & Administration

Initial Dosage: CKD Stages 3 and 4
 (
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
Baseline iPTH Level
Daily Dose
Three Times a Week Dose*
Less than or equal to 500 pg/mL1 mcg2 mcg
More than 500 pg/mL2 mcg4 mcg
*   To be administered not more often than every other day

Dose Titration

Table 2. Recommended ZEMPLAR Dose Titration Base upon iPTH Level
Dose Adjustment at 2 to 4 Week Intervals
iPTH Level Relative to Baseline
ZEMPLAR Capsule Dose
Daily Dosage
Three Times a Week Dosage*
The same, increased or
decreased by less than 30%
Increase dose by1 mcg2 mcg
Decreased by more than or equal to 30% and less than or equal to 60%Maintain dose--
Decreased by more than 60% or

iPTH less than 60 pg/mL
Decrease dose by1 mcg2 mcg
*   To be administered not more often than every other day

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.

,
2.3 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.

)
Adult: Baseline iPTH ≤ 500 pg/mL1 mcg orally daily or 2 mcg three times a week*
Adult: Baseline iPTH > 500 pg/mL 2 mcg orally daily or 4 mcg three times a week*
Pediatric: Ages 10 to 16 years1 mcg orally three times a week*
Dose Titration: CKD Stages 3 and 4
 (
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
Baseline iPTH Level
Daily Dose
Three Times a Week Dose*
Less than or equal to 500 pg/mL1 mcg2 mcg
More than 500 pg/mL2 mcg4 mcg
*   To be administered not more often than every other day

Dose Titration

Table 2. Recommended ZEMPLAR Dose Titration Base upon iPTH Level
Dose Adjustment at 2 to 4 Week Intervals
iPTH Level Relative to Baseline
ZEMPLAR Capsule Dose
Daily Dosage
Three Times a Week Dosage*
The same, increased or

decreased by less than 30%
Increase dose by1 mcg2 mcg
Decreased by more than or equal to 30% and less than or equal to 60%Maintain dose--
Decreased by more than 60% or

iPTH less than 60 pg/mL
Decrease dose by1 mcg2 mcg
*   To be administered not more often than every other day

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.

,
2.3 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.

)
Adult: iPTH same, increased or decreased by < 30% relative to baseline Increase dose by 1 mcg daily or 2 mcg three times a week*
Adult: iPTH decreased by ≥ 30% and ≤ 60% relative to baseline Maintain dose
Adult: iPTH decreased by > 60% or iPTH < 60 pg/mL relative to baseline Decrease dose by 1 mcg daily or 2 mcg three times a week*
Pediatric: Ages 10 to 16 yearsIncrease each dose by 1 mcg three times a week every 4 weeks or decrease each dose by 1 mcg three times a week at any time based on iPTH, serum calcium and phosphorus levels.*
* Not more frequently than every other day when dosing three times a week.
Initial Dosage: CKD Stage 5
 (
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.

)
Adult Dose (micrograms) = baseline iPTH (pg/mL) divided by 80. Administer dose orally three times a week.*
Pediatric: Ages 10 to 16 yearsDose (micrograms) = baseline iPTH (pg/mL) divided by 120. Administer dose orally three times a week.*
Dose Titration: CKD Stage 5
 (
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.

)
Adult Dose in micrograms is based on most recent iPTH (pg/mL) divided by 80 with adjustments based on serum calcium and phosphorous levels. Dose three times a week.*
Pediatric: Ages 10 to 16 years Increase each dose by 1 mcg three times a week every 4 weeks or decrease each dose by 2 mcg three times a week at any time based on iPTH, serum calcium and phosphorus levels.*
* Not more frequently than every other day.

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