OVERDOSAGE
Overdosage of Zemplar may lead to hypercalcemia, hypercalciuria, hyperphosphatemia, and over suppression of PTH. (see WARNINGS ).

Treatment of Overdosage and Hypercalcemia
The treatment of acute overdosage should consist of general supportive measures. Serial serum electrolyte determinations (especially calcium), rate of urinary calcium excretion, and assessment of electrocardiographic abnormalities due to hypercalcemia should be obtained. Such monitoring is critical in patients receiving digitalis. Discontinuation of supplemental calcium and institution of a low calcium diet are also indicated in acute overdosage.

General treatment of hypercalcemia due to overdosage consists of immediate dose reduction or suspension of Zemplar therapy, institution of a low calcium diet, withdrawal of calcium supplements, patient mobilization, and attention to fluid and electrolyte imbalances. Serum calcium levels should be determined at least weekly until normocalcemia ensues. When serum calcium levels have returned to within normal limits, Zemplar may be reinitiated at a lower dose. If persistent and markedly elevated serum calcium levels occur, there are a variety of therapeutic alternatives that may be considered. These include the use of drugs such as phosphates and corticosteroids as well as measures to induce diuresis. Also, one may consider dialysis against a calcium-free dialysate.

Zemplar is not significantly removed by dialysis.

DOSAGE AND ADMINISTRATION
The currently accepted target range for iPTH levels in CKD Stage 5 patients is no more than 1.5 to 3 times the non-uremic upper limit of normal.

The recommended initial dose of Zemplar is 0.04 mcg/kg to 0.1 mcg/kg (2.8 – 7 mcg) administered as a bolus dose no more frequently than every other day at any time during dialysis.

If a satisfactory response is not observed, the dose may be increased by 2 to 4 mcg at 2- to 4-week intervals. During any dose adjustment period, serum calcium and phosphorus levels should be monitored more frequently, and if an elevated calcium level or a Ca × P product greater than 75 is noted, the drug dosage should be immediately reduced or interrupted until these parameters are normalized. Then, Zemplar should be reinitiated at a lower dose. If a patient is on a calcium-based phosphate binder, the dose may be decreased or withheld, or the patient may be switched to a non-calcium-based phosphate binder. Zemplar doses may need to be decreased as the PTH levels decrease in response to therapy. Thus, incremental dosing must be individualized.

The following table is a suggested approach in dose titration:

Suggested Dosing Guidelines PTH Level Zemplar Dose
the same or increasing increase
decreasing by < 30% increase
decreasing by > 30%, < 60% maintain
decreasing by > 60% decrease
one and one-half to three times upper limit of normal maintain

The influence of mild to moderately impaired hepatic function on paricalcitol pharmacokinetics is sufficiently small that no dosing adjustment is required.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

After initial vial use, the contents of the multi-d