cinacalcet

REMS

Secondary hyperparathyroidism in patients with chronic kidney disease on dialysis.
Hypercalcemia caused by parathyroid carcinoma.
Severe hypercalcemia in patients with primary hyperparathyroidism who are unable to undergo parathyroidectomy.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Hypocalcemia.

Use Cautiously in:

History of seizure disorder (↑ risk of seizures with hypocalcemia);
Chronic kidney disease patients who are not being dialyzed (↑ risk of hypocalcemia);
Intact parathyroid hormone (iPTH) level <150 pg/mL (dose ↓ or discontinuation may be warranted);
Moderate or severe hepatic impairment;
Congenital long QT syndrome, QT interval prolongation, family history of long QT syndrome or sudden cardiac death, or concurrent use of QT-interval-prolonging medications;
OB: Safety not established in pregnancy;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: ARRHYTHMIA, HF exacerbation, hypotension, QT interval prolongation, TORSADES DE POINTES

F and E: HYPOCALCEMIA

GI: nausea, vomiting

Metab: adynamic bone disease

Neuro: SEIZURES

Interactions ⬆ ⬇

Drug-drug:

Concurrent use of QT interval prolonging medications may ↑ risk of QT interval prolongation and/or torsade de pointes, especially in patients with hypocalcemia.
May ↑ levels and risk of toxicity of CYP2D6 substrates, including flecainide, vinblastine, thioridazine, metoprolol, carvedilol, and most tricyclic antidepressants; dose adjustments may be necessary.
Strong CYP3A4 inhibitors, including ketoconazole, itraconazole, and erythromycin, may ↑ levels and risk of toxicity; monitoring and dose adjustment may be necessary.

Availability ⬆ ⬇

(Generic available)

Tablets: 30 mg; 60 mg; 90 mg

Route/Dosage ⬆ ⬇

Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease on Dialysis

PO (Adults ): 30 mg once daily; may ↑ dose every 2–4 wk (dose range 30–180 mg once daily) based on iPTH levels. Switching from etecalcetide: Discontinue etecalcetide for ≥4 wk and ensure corrected serum calcium is at or above lower limit of normal prior to starting cinacalcet.

Parathyroid Carcinoma or Primary Hyperparathyroidism

PO (Adults ): 30 mg twice daily; may ↑ every 2–4 wk up to 90 mg 3–4 times daily based on serum calcium levels.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Increases sensitivity of calcium-sensing receptors located on the surface of chief cells of parathyroid gland to levels of extracellular calcium. This decreases parathyroid hormone (PTH) production with resultant decrease in serum calcium.

Therapeutic effects:

Decreased bone turnover and fibrosis.
Decreased serum calcium.

Classifications ⬆ ⬇

Therapeutic Classification: hypocalcemics

Pharmacologic Classification: calcimimetic agents

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed following oral administration; absorption is enhanced by food and further enhanced by a high-fat meal.

Distribution: Extensively distributed to tissues.

Protein Binding: 93–97%.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A4, CYP2D6, and CYP1A2 isoenzymes; 80% excreted in urine as metabolites, 15% in feces.

Half-Life: 30–40 hr.

Time/Action Profile ⬆ ⬇

(effect on PTH levels)

ROUTE	ONSET	PEAK	DURATION
PO	rapid	2–6 hr	6–12 hr

Patient/Family Teaching ⬆ ⬇

Instruct patient to take cinacalcet as directed.
Advise patient to report signs and symptoms of hypocalcemia, GI bleeding (black tarry stools, abdominal pain), nausea, and vomiting to health care professional promptly.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breastfeeding.
Emphasize the importance of follow-up lab tests to monitor safely and efficacy.

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Indications ⬇