cinacalcet (Rx)

>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

Postmarketing Reports

Hypotension

Worsening heart failure and/or arrhythmias

Adynamic bone disease

Gastrointestinal bleeding

Contraindications

Hypersensitivity

Should not be initiated in severe hypocalcemia (serum Ca

Cautions

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

Cases of gastrointestinal bleeding, mostly upper gastrointestinal bleeding, reported in patients using calcimimetics, the exact cause of GI bleeding is unknown; patients with risk factors for upper GI bleeding (such as known gastritis, esophagitis, ulcers or severe vomiting) may be at increased risk for GI bleeding when receiving treatment; monitor patients for worsening of common GI adverse reactions of nausea and vomiting associated with therapy and for signs and symptoms of GI bleeding and ulcerations during therapy; promptly evaluate and treat any suspected GI bleeding

Adynamic bone disease may develop if PTH levels <100 pg/mL

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; life threatening events and fatal outcomes associated with hypocalcemia reported in patients receiving treatment, including in pediatric patients

QT interval prolongation and ventricular arrhythmia

• Decreases in serum calcium can prolong the QT interval, potentially resulting in ventricular arrhythmia; cases of QT prolongation and ventricular arrhythmia reported in patients receiving therapy; patients with congenital long QT syndrome
• History of QT interval prolongation, family history of long QT syndrome or sudden cardiac death, and other conditions that predispose to QT interval prolongation and ventricular arrhythmia may be at increased risk for QT interval prolongation and ventricular arrhythmias if they develop hypocalcemia; closely monitor corrected serum calcium and QT interval in patients at risk receiving therapy

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

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Increases sensitivity of Ca-sensing receptor in parathyroid cells to activation by extracellular Ca, thereby downregulating PTH levels and consequently lowering serum Ca & phosphorus

Absorption

Bioavailability: High fat meal increases both peak plasma concentration and AUC vis-a-vis fasting

Peak Plasma Time: 2-6 hr

Distribution

Protein Bound: 93-97%

Vd: 1000 L

Metabolism

Metabolism: metabolized by CYP3A4, CYP2D6 & CYP1A2

Metabolites: hydrocinnamic and hydroxy-hydrocinnamic acid, naphthalene-ring-containing molecules, dihydrodiols

Enzyme Inhibited: CYP2D6

Elimination

Half-Life: 30-40 hr

Excretion: Urine (80%); feces (15%)

Oral Administration

Take with food or shortly after meal

Swallow tablet whole, do not chew, crush, or divide