Paricalcitol: Package Insert and Label Information

PARICALCITOL- paricalcitol capsule
Bryant Ranch Prepack

Structural FormulaFigure 1Figure 2

1 INDICATIONS AND USAGE

1.1 Chronic Kidney Disease Stages 3 and 4

Paricalcitol capsules are indicated in adults for the prevention and treatment of secondary hyperparathyroidism associated with Chronic Kidney Disease (CKD) Stages 3 and 4.

Pediatric use information for patients 10 to 16 years of age is approved for AbbVie Inc.’s Zemplar (paricalcitol) capsules. However, due to AbbVie Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

1.2 Chronic Kidney Disease Stage 5

Paricalcitol capsules are indicated in adults for the prevention and treatment of secondary hyperparathyroidism associated with CKD Stage 5 in patients on hemodialysis (HD) or peritoneal dialysis (PD).

Pediatric use information for patients 10 to 16 years of age is approved for AbbVie Inc.’s Zemplar (paricalcitol) capsules. However, due to AbbVie Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

2 DOSAGE AND ADMINISTRATION

2.1 Chronic Kidney Disease Stages 3 and 4 in Adults

Administer paricalcitol 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 Paricalcitol Capsules Starting Dose Based upon Baseline iPTH Level

Baseline iPTH Level

Daily Dose

Three Times a Week Dose*

Less than or equal to 500 pg/mL

1 mcg

2 mcg

More than 500 pg/mL

2 mcg

4 mcg

*To be administered not more often than every other day

Dose Titration

Table 2. Recommended Paricalcitol Capsules Dose Titration Base upon iPTH Level

Dose Adjustment at 2 to 4 Week Intervals

iPTH Level Relative to Baseline

Paricalcitol

Capsule Dose

Daily

Dosage

Three Times a Week Dosage*

The same, increased or decreased by less than 30%

Increase dose by

1 mcg

2 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 by

1 mcg

2 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.

2.2 Chronic Kidney Disease Stage 5 in Adults

Initial Dose

Administer the dose of paricalcitol 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 paricalcitol based on iPTH, serum calcium and phosphorus levels. Titrate paricalcitol 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.

Pediatric use information for patients 10 to 16 years of age is approved for AbbVie Inc.’s Zemplar (paricalcitol) capsules. However, due to AbbVie Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

2.4 Monitoring

Monitor serum calcium and phosphorus levels closely after initiation of paricalcitol, 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 paricalcitol should be reduced or withheld until these parameters are normalized.

2.5 Administration

Paricalcitol capsules may be taken without regard to food.

3 DOSAGE FORMS AND STRENGTHS

Paricalcitol capsules are available as 1 mcg, 2 mcg, and 4 mcg soft gelatin capsules.

  • 1 mcg: oval, gray capsule imprinted with “PA1”
  • 2 mcg: oval, orange-brown capsule imprinted with “PA2”
  • 4 mcg: oval, yellow capsule imprinted with “PA4”

4 CONTRAINDICATIONS

Paricalcitol capsules should not be given to patients with evidence of

  • hypercalcemia or

  • vitamin D toxicity [see Warnings and Precautions (5.1) ].

5 WARNINGS AND PRECAUTIONS

Excessive administration of vitamin D compounds, including paricalcitol capsules, can cause over suppression of PTH, hypercalcemia, hypercalciuria, hyperphosphatemia, and adynamic bone disease.

5.1 Hypercalcemia

Progressive hypercalcemia due to overdosage of vitamin D and its metabolites may be so severe as to require emergency attention [see Overdosage (10) ]. Acute hypercalcemia may exacerbate tendencies for cardiac arrhythmias and seizures and may potentiate the action of digitalis. Chronic hypercalcemia can lead to generalized vascular calcification and other soft-tissue calcification. Concomitant administration of high doses of calcium-containing preparations or thiazide diuretics with paricalcitol may increase the risk of hypercalcemia. High intake of calcium and phosphate concomitant with vitamin D compounds may lead to serum abnormalities requiring more frequent patient monitoring and individualized dose titration. Patients also should be informed about the symptoms of elevated calcium, which include feeling tired, difficulty thinking clearly, loss of appetite, nausea, vomiting, constipation, increased thirst, increased urination and weight loss.

Prescription-based doses of vitamin D and its derivatives should be withheld during paricalcitol treatment to avoid hypercalcemia.

5.2 Digitalis Toxicity

Digitalis toxicity is potentiated by hypercalcemia of any cause. Use caution when paricalcitol capsules are prescribed concomitantly with digitalis compounds.

5.3 Laboratory Tests

During the initial dosing or following any dose adjustment of medication, serum calcium, serum phosphorus, and serum or plasma iPTH should be monitored at least every two weeks for 3 months, then monthly for 3 months, and every 3 months thereafter.

In pre-dialysis patients, paricalcitol capsules may increase serum creatinine and therefore decrease the estimated GFR (eGFR). Similar effects have also been seen with calcitriol.

5.4 Aluminum Overload and Toxicity

Aluminum-containing preparations (e.g., antacids, phosphate binders) should not be administered chronically with paricalcitol, as increased blood levels of aluminum and aluminum bone toxicity may occur.

6 ADVERSE REACTIONS

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

6.1 Clinical Trials Experience

CKD Stages 3 and 4

Adults

The safety of paricalcitol capsules has been evaluated in three 24-week (approximately six‑month), double-blind, placebo-controlled, multicenter clinical studies involving 220 CKD Stages 3 and 4 patients. Six percent (6%) of paricalcitol capsules-treated patients and 4% of placebo-treated patients discontinued from clinical studies due to an adverse event. Adverse events occurring in the paricalcitol capsules group at a frequency of 2% or greater and more frequently than in the placebo group are presented in Table 3:

Table 3. Adverse Reactions by Body System Occurring in ≥ 2% of Subjects in the Paricalcitol-Treated Group of Three, Double-Blind, Placebo-Controlled CKD Stages 3 and 4 Studies

Number (%) of Subjects

Adverse Eventa

Paricalcitol Capsules

(n = 107)

Placebo

(n = 113)

Overall

88

(82%)

86

(76%)

Ear and Labyrinth Disorders

Vertigo

5

(5%)

0

(0%)

Gastrointestinal Disorders

Abdominal Discomfort

4

(4%)

1

(1%)

Constipation

4

(4%)

4

(4%)

Diarrhea

7

(7%)

5

(4%)

Nausea

6

(6%)

4

(4%)

Vomiting

5

(5%)

5

(4%)

General Disorders and Administration Site Conditions

Chest Pain

3

(3%)

1

(1%)

Edema

6

(6%)

5

(4%)

Pain

4

(4%)

4

(4%)

Immune System Disorders

Hypersensitivity

6

(6%)

2

(2%)

Infections and Infestations

Fungal Infection

3

(3%)

0

(0%)

Gastroenteritis

3

(3%)

3

(3%)

Infection

3

(3%)

3

(3%)

Sinusitis

3

(3%)

1

(1%)

Urinary Tract Infection

3

(3%)

1

(1%)

Viral Infection

8

(7%)

8

(7%)

Metabolism and Nutrition Disorders

Dehydration

3

(3%)

1

(1%)

Musculoskeletal and Connective Tissue Disorders

Arthritis

5

(5%)

0

(0%)

Back Pain

3

(3%)

1

(1%)

Muscle Spasms

3

(3%)

0

(0%)

Nervous System Disorders

Dizziness

5

(5%)

5

(4%)

Headache

5

(5%)

5

(4%)

Syncope

3

(3%)

1

(1%)

Psychiatric Disorders

Depression

3

(3%)

0

(0%)

Respiratory, Thoracic and Mediastinal Disorders

Cough

3

(3%)

2

(2%)

Oropharyngeal Pain

4

(4%)

0

(0%)

Skin and Subcutaneous Tissue Disorders

Pruritus

3

(3%)

3

(3%)

Rash

4

(4%)

1

(1%)

Skin Ulcer

3

(3%)

0

(0%)

Vascular Disorders

Hypertension

7

(7%)

4

(4%)

Hypotension

5

(5%)

3

(3%)

a. Includes only events more common in the paricalcitol treatment group.

Additional Adverse Reactions

The following additional adverse reactions occurred in <2% of the paricalcitol-treated adult patients in the above double-blind, placebo-controlled clinical trial.

Gastrointestinal Disorders: Dry mouth

Investigations: Hepatic enzyme abnormal

Nervous System Disorders: Dysgeusia

Skin and Subcutaneous Tissue Disorders: Urticaria

Pediatric use information for patients 10 to 16 years of age is approved for AbbVie Inc.’s Zemplar (paricalcitol) capsules. However, due to AbbVie Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

CKD Stage 5

Adults

The safety of paricalcitol capsules has been evaluated in one 12-week, double-blind, placebo-controlled, multicenter clinical study involving 88 CKD Stage 5 patients. Sixty-one patients received paricalcitol capsules and 27 patients received placebo.

The proportion of patients who terminated prematurely from the study due to adverse events was 7% for paricalcitol capsules-treated patients and 7% for placebo patients.

Adverse events occurring in the paricalcitol capsules group at a frequency of 2% or greater and more frequently than in the placebo group are as follows:

Table 5. Adverse Reactions by Body System Occurring in ≥ 2% of Subjects in the Paricalcitol-Treated Group, Double-Blind, Placebo-Controlled CKD Stage 5 Study

Number (%) of Subjects

Adverse Eventsa

Paricalcitol Capsules

(n=61)

Placebo

(n = 27)

Overall

43

(70%)

19

(70%)

Gastrointestinal Disorders

Constipation

3

(5%)

0

(0%)

Diarrhea

7

(11%)

3

(11%)

Vomiting

4

(7%)

0

(0%)

General Disorders and Administration Site Conditions

Fatigue

2

(3%)

0

(0%)

Edema Peripheral

2

(3%)

0

(0%)

Infections and Infestations

Nasopharyngitis

5

(8%)

2

(7%)

Peritonitis

3

(5%)

0

(0%)

Sinusitis

2

(3%)

0

(0%)

Urinary Tract Infection

2

(3%)

0

(0%)

Metabolism and Nutrition Disorders

Fluid Overload

3

(5%)

0

(0%)

Hypoglycemia

2

(3%)

0

(0%)

Nervous System Disorders

Dizziness

4

(7%)

0

(0%)

Headache

2

(3%)

0

(0%)

Psychiatric Disorders

Anxiety

2

(3%)

0

(0%)

Insomnia

3

(5%)

0

(0%)

Renal and Urinary Disorders

Renal Failure Chronic

2

(3%)

0

(0%)

a. Includes only events more common in the paricalcitol treatment group.

Additional Adverse Reactions

The following adverse reactions occurred in <2% of the paricalcitol-treated patients in the above double-blind, placebo-controlled clinical trial.

Gastrointestinal Disorders: Gastroesophageal reflux disease

Metabolism and Nutrition Disorders: Decreased appetite, hypercalcemia, hypocalcemia

Reproductive System and Breast Disorders: Breast tenderness

Skin and Subcutaneous Tissue Disorders: Acne

Pediatric use information for patients 10 to 16 years of age is approved for AbbVie Inc.’s Zemplar (paricalcitol) capsules. However, due to AbbVie Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

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