Paricalcitol (2 brand names, 3 dosage forms, 3 routes)
Available dosage forms: SOLUTION, CAPSULE, INJECTABLE.
Routes of administration: INTRAVENOUS, ORAL, INJECTION.
Brand Names
- PARICALCITOL
- ZEMPLAR
Contraindications
ZEMPLAR capsules should not be given to patients with evidence of hypercalcemia or vitamin D toxicity [see Warnings and Precautions ( 5.1 )].
Warnings and Precautions
Excessive administration of vitamin D compounds, including ZEMPLAR capsules, can cause over suppression of PTH, hypercalcemia, hypercalciuria, hyperphosphatemia, and adynamic bone disease.
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.
Drug Interactions
Table 6 shows the clinically significant drug interactions with ZEMPLAR capsules. Table 6: Clinically Significant Drug Interactions with Paricalcitol CYP3A Inhibitors Clinical Impact Paricalcitol is partially metabolized by CYP3A. Hence, exposure of paricalcitol will increase upon coadministration with strong CYP3A inhibitors such as but not limited to: boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole. Intervention Dose adjustment of ZEMPLAR capsules may be necessary. Monitor closely for iPTH and serum calcium concentrations, if a patient initiates or discontinues therapy with a strong CYP3A4 inhibitor. Cholestyramine Clinical Impact Drugs that impair intestinal absorption of fat-soluble vitamins, such as cholestyramine, may interfere with the absorption of paricalcitol. Intervention Recommend to take ZEMPLAR capsules at least 1 hour before or 4 to 6 hours after taking cholestyramine (or at as great an interval as possible) to avoid impeding absorption of paricalcitol. Mineral Oil Clinical Impact Mineral oil or other substances that may affect absorption of fat may influence the absorption of paricalcitol. Intervention Recommend to take ZEMPLAR capsules at least 1 hour before or 4 to 6 hours after taking mineral oil (or at as great an interval as possible) to avoid affecting absorption of paricalcitol.
Mechanism of Action
Paricalcitol is a synthetic, biologically active vitamin D2 analog of calcitriol. Preclinical and in vitro studies have demonstrated that paricalcitol’s biological actions are mediated through binding of the VDR, which results in the selective activation of vitamin D responsive pathways. Vitamin D and paricalcitol have been shown to reduce parathyroid hormone levels by inhibiting PTH synthesis and secretion.
Overdosage
Excessive administration of ZEMPLAR capsules can cause hypercalcemia, hypercalciuria, and hyperphosphatemia, and over suppression of PTH [see Warnings and Precautions ( 5.1 )]. Treatment of Overdosage The treatment of acute overdosage of ZEMPLAR capsules should consist of general supportive measures. If drug ingestion is discovered within a relatively short time, induction of emesis or gastric lavage may be of benefit in preventing further absorption. If the drug has passed through the stomach, the administration of mineral oil may promote its fecal elimination. 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 accidental overdosage. Due to the relatively short duration of the pharmacological action of paricalcitol, further measures are probably unnecessary. If persistent and markedly elevated serum calcium levels occur, there are a variety of therapeutic alternatives that may be considered depending on the patient’s underlying condition. These include the use of drugs such as phosphates and corticosteroids, as well as measures to induce an appropriate forced diuresis. Paricalcitol is not significantly removed by dialysis.