with Zemplar Capsules was 6.6% as compared to 0% for patients given placebo. In PD patients the incidences of hypercalcemia in patients treated with Zemplar Capsules was 21% as compared to 0% for patients given placebo. The pattern of change in the mean values for serum iPTH during the studies are shown in Figure 2. The rate of hypercalcemia with Zemplar Capsules may be reduced with a lower dosing regimen based on the iPTH/80 formula as shown by computer simulations. The hypercalcemia rate can be further predicted to decrease, if the treatment is initiated in only those with baseline serum calcium ≤ 9.5 mg/dL. (see CLINICAL PHARMACOLOGY; Pharmacodynamics and DOSAGE AND ADMINISTRATION; CKD Stage 5)
Figure 2. Mean Values for Serum iPTH Over Time in a Phase 3, Double-Blind, Placebo-Controlled CKD Stage 5 Study
INDICATIONS AND USAGE
Zemplar Capsules are indicated for the prevention and treatment of secondary hyperparathyroidism associated with chronic kidney disease (CKD) Stage 3 and 4, and CKD Stage 5 patients on hemodialysis (HD) or peritoneal dialysis (PD).
CONTRAINDICATIONS
Zemplar Capsules should not be given to patients with evidence of vitamin D toxicity, hypercalcemia, or hypersensitivity to any ingredient in this product (see WARNINGS).
WARNINGS
Excessive administration of vitamin D compounds, including Zemplar Capsules, can cause over suppression of PTH, hypercalcemia, hypercalciuria, hyperphosphatemia, and adynamic bone disease. Progressive hypercalcemia due to overdosage of vitamin D and its metabolites may be so severe as to require emergency attention. 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. High intake of calcium and phosphate concomitant with vitamin D compounds may lead to similar abnormalities and patient monitoring and individualized dose titration is required.
Pharmacologic doses of vitamin D and its derivatives should be withheld during Zemplar treatment to avoid hypercalcemia.
PRECAUTIONS
General
Digitalis toxicity is potentiated by hypercalcemia of any cause, so caution should be applied when digitalis compounds are prescribed concomitantly with Zemplar Capsules.
Information for Patients
The patient or guardian should be informed about compliance with dosage instructions, adherence to instructions about diet and phosphorus restriction, and avoidance of the use of unapproved nonprescription drugs. Phosphate-binding agents may be needed to control serum phosphorus levels in patients, but excessive use of aluminum containing compounds should be avoided. Patients also should be informed about the symptoms of elevated calcium (see ADVERSE REACTIONS).
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 after initiation of Zemplar therapy or following dose-adjustments in Zemplar therapy, then monthly for 3 months, and every 3 months thereafter.
Drug Interactions
Paricalcitol is not expected to inhibit the clearance of drugs metabolized by cytochrome P450 enzymes CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A nor induce the clearance of drugs metabolized by CYP2B6, CYP2C9 or CYP3A.
A multiple dose drug-drug interaction stu |
