Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease on Dialysis

In 3 double-blind placebo-controlled clinical trials, 1126 CKD patients on dialysis received study drug (656 Sensipar, 470 placebo) for up to 6 months. The most frequently reported adverse events (incidence of at least 5% in the Sensipar group and greater than placebo) are provided in Table 2. The most frequently reported events in the Sensipar group were nausea and vomiting.

Table 2. Adverse Event Incidence ( ≥ 5%) in Patients on Dialysis

The incidence of serious adverse events (29% vs. 31%) was similar in the Sensipar and placebo groups, respectively.

12-Month Experience with Sensipar: Two hundred and sixty-six patients from 2 phase 3 studies continued to receive Sensipar or placebo treatment in a 6-month double-blind extension study (12-month total treatment duration). The incidence and nature of adverse events in this study were similar in the two treatment groups, and comparable to those observed in the phase 3 studies.

Postmarketing Experience with Sensipar: Rash and hypersensitivity have been identified as adverse reactions during post-approval use of Sensipar. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Parathyroid Carcinoma

The most frequent adverse events in this patient group were nausea and vomiting.

Laboratory values: Serum calcium levels should be closely monitored in patients receiving Sensipar (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).

Drug/Laboratory Test Interactions

See CLINICAL PHARMACOLOGY, Pharmacokinetics and Drug Interactions.

Effect of Sensipar on other drugs:

Drugs metabolized by cytochrome P450 2D6 (CYP2D6): Sensipar is a strong in vitro, as well as in vivo, inhibitor of CYP2D6. Therefore, dose adjustments of concomitant medications that are predominantly metabolized by CYP2D6 and have a narrow therapeutic index (e.g., flecainide, vinblastine, thioridazine and most tricyclic antidepressants) may be required.

Desipramine: Concurrent administration of cinacalcet (90 mg) with desipramine (50 mg) increased the exposure of desipramine by 3.6 fold in CYP2D6 extensive metabolizers.

Amitriptyline: Concurrent administration of 25 mg or 100 mg cinacalcet with 50 mg amitriptyline increased amitriptyline exposure and nortriptyline (active metabolite) exposure by approximately 20% in CYP2D6 extensive metabolizers.

Effect of other drugs on Sensipar:

Sensipar is metabolized by multiple cytochrome P450 enzymes, primarily CYP3A4, CYP2D6, and CYP1A2.

Ketoconazole: Sensipar is metabolized in part by CYP3A4. Co-administration of ketoconazole, a strong inhibitor of CYP3A4, increased cinacalcet exposure following a single 90 mg dose of Sensipar by 2.3 fold. Dose adjustment of Sensipar may be required and PTH and serum calcium concentrations should be closely monitored if a patient initiates or discontinues therapy with a strong CYP3A4 inhibitor (e.g., ketoconazole, erythromycin, itraconazole; see DOSAGE AND ADMINISTRATION).

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