Zemplar has been evaluated for safety in clinical studies in 454 CKD Stage 5 patients. In four, placebo-controlled, double-blind, multicenter studies, discontinuation of therapy due to any adverse event occurred in 6.5% of 62 patients treated with Zemplar (dosage titrated as tolerated, see CLINICAL PHARMACOLOGY, Clinical Studies) and 2.0% of 51 patients treated with placebo for 1 to 3 months. Adverse events occurring with greater frequency in the Zemplar group at a frequency of 2% or greater, regardless of causality, are presented in the following table:

A patient who reported the same medical term more than once was counted only once for that medical term.

Safety parameters (changes in mean Ca, P, Ca x P) in an open-label safety study up to 13 months in duration support the long-term safety of Zemplar in this patient population.

Potential adverse events of Zemplar Injection are, in general, similar to those encountered with excessive vitamin D intake. Signs and symptoms of vitamin D intoxication associated with hypercalcemia include:

Early
Weakness, headache, somnolence, nausea, vomiting, dry mouth, constipation, muscle pain, bone pain, and metallic taste.

Late
Anorexia, weight loss, conjunctivitis (calcific), pancreatitis, photophobia, rhinorrhea, pruritus, hyperthermia, decreased libido, elevated BUN, hypercholesterolemia, elevated AST and ALT, ectopic calcification, hypertension, cardiac arrhythmias, somnolence, death, and rarely, overt psychosis.

Adverse events during post-marketing experience:Taste perversion, such as metallic taste, and allergic reactions, such as rash, urticaria, pruritus, facial and oral edema rarely have been reported.

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 drug metabolized by CYP2B6, CYP2C9 or CYP3A.

Specific interaction studies were not performed with Zemplar Injection.

A multiple dose drug-drug interaction study with ketoconazole and paricalcitol capsule demonstrated that ketoconazole approximately doubled paricalcitol AUC_0-¥ (see CLINICAL PHARMACOLOGY). Since paricalcitol is partially metabolized by CYP3A and ketoconazole is known to be a strong inhibitor of cytochrome P450 3A enzyme, care should be taken while dosing paricalcitol with ketoconazole and other strong P450 3A inhibitors including atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin or voriconazole.

Digitalis toxicity is potentiated by hypercalcemia of any cause, so caution should be applied when digitalis compounds are prescribed concomitantly with Zemplar.

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