Cinacalcet

Hyperparathyroidism, Hypercalcemia, Parathyroid carcinoma

Secondary Hyperparathyroidism (HPT) Indicated for secondary HPT in patients with chronic kidney disease on dialysis Initial dose: 30 mg PO once daily. May increase if needed by titrating at 2-4 week intervals through sequential doses of 60, 90, 120, or 180 mg once daily. Hypercalcemia in Patients with Parathyroid Carcinoma Initial dose: 30 mg PO twice daily. May increase if needed at 2-4 week intervals through sequential doses 60 mg twice daily, 90 mg q12hr, or 90 mg q6-8hr as necessary to normalize serum calcium levels Hypercalcemia With Primary Hyperparathyroidism (HPT) Indicated for severe hypercalcemia in patients with primary HPT who are unable to undergo parathyroidectomy Initial dose: 30 mg PO twice daily. May increase if needed at 2-4 week intervals through sequential doses 60 mg twice daily, 90 mg q12hr, or 90 mg q6-8hr as necessary to normalize serum calcium levels

Renal Impairment Dose adjustment not necessary

Hepatic impairment: Moderate to severe hepatic impairment: Monitor serum calcium, serum phosphorus, and iPTH levels throughout treatment

Should be taken with food. Take w/ food or shortly after food. Swallow whole, do not divide.

Hypersensitivity.

History of seizure; seizures (primarily generalized or tonic-clonic) were observed in clinical trials (1.4% compared with 0.7% in placebo) Not for therapy of patients with chronic kidney disease not on dialysis due to increased risk for hypokalemia Drug exposure is increased in patients with moderate and severe hepatic impairment; monitor serum calcium, serum phosphorus, and intact parathyroid hormone closely Adynamic bone disease may develop; if iPTH levels decrease below 150 pg/mL in patients receiving therapy, the dose and/or vitamin D sterols should be reduced or therapy discontinued Therapy is not indicated for patients with CKD not on dialysis ; long-term safety and efficacy of therapy not established in patients with secondary HPT and CKD not on dialysis Idiosyncratic cases of hypotension, worsening heart failure, and/or arrhythmia reported in patients with impaired cardiac function, in which a causal relationship to therapy could not be completely excluded and which may be mediated by reductions in serum calcium levels Significant lowering of calcium by therapy can cause paresthesias, myalgias, muscle spasms, tetany, and seizures; QT interval prolongation and ventricular arrhythmia; life-threatening events and fatal outcomes associated with hypocalcemia reported, including in pediatric patients Monitoring Parameters Monitor for hypocalcemia once maintenance dose established Primary hyperparathyroidism and parathyroid carcinoma Measure serum-calcium concentration before initiation of treatment and within 1 week after starting treatment or adjusting dose, then every 2–3 months. Hyperparathyroidism in patients with CKD on dialysis Serum calcium and serum phosphorus should be measured within 1 week and intact parathyroid hormone (iPTH) should be measured 1 to 4 weeks after initiation or dose adjustment of dose Drug should be titrated no more frequently than every 2 to 4 weeks through sequential doses of 30, 60, 90, 120, and 180 mg once daily to target

Not Classi Pregnancy Limited case reports of use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes; in animal reproduction studies, when female rats were exposed to the drug during the period of organogenesis through to weaning at 2-3 times systemic drug levels (based on AUC) at maximum recommended human dose (MRHD) of 180 mg/day, peripartum and early postnatal pup loss and reduced pup body weight gain were observed in the presence of maternal hypocalcemia Lactation There are no data regarding presence in human milk or effects on breastfed infant or on milk production; studies in rats showed that cinacalcet was excreted in milk; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition

Cinacalcet is a strong CYP2D6 inhibitor and may increase serum concentrations of amitriptyline, nortriptyline and desipramine. Cinacalcet may decrease serum concentrations of tacrolimus. CYP3A4 inhibitors such as ketoconazole, erythromycin may increase plasma concentrations of Cinacalcet. Concurrent administration with calcium-lowering drugs including other calcium-sensing receptor agonists could result in severe hypocalcemia; closely monitor serum calcium in patients receiving the drug therapy and concomitant therapies known to lower serum calcium levels Contraindicated (3) eliglustat etelcalcetide mavorixafor Serious (17) carbamazepine cimetidine clarithromycin dacomitinib erythromycin base erythromycin ethylsuccinate erythromycin lactobionate erythromycin stearate givosiran ketoconazole levoketoconazole metoclopramide intranasal nefazodone rifabutin rifampin sofpironium topical St John's Wort

>10% Secondary Parathyroidism Diarrhea (20%),Nausea (19%),Vomiting (15%),Myalgia (14%) 1-10% Secondary Parathyroidism Dizziness (8%),Hypertension (5%),Access infection (4%),Anorexia (4%),Asthenia (4%),Noncardiac chest pain (4%),Seizures 1.4% Frequency Not Defined Parathyroid CA Nausea/vomiting,Hypocalcemia Potentially Fatal: Hypersensitivity reaction including angioedema.

Cinacalcet is a calcimimetic agent. It lowers parathyroid hormone (PTH) secretion by increasing the sensitivity of the calcium-sensing receptor of the parathyroid gland to activation by extracellular calcium. PTH reduction leads to concomitant decrease in serum calcium and phosphorus concentrations.