Dosing & Uses
Dosage Forms & Strengths
tablet
- 30mg
- 60mg
- 90mg
Primary Hyperparathyroidism (HPT)
Indicated for severe hypercalcemia in patients with primary HPT who are unable to undergo parathyroidectomy
Initial dose: 30 mg PO q12hr
May increase if needed at 2-4 week intervals through sequential doses 60 mg q12hr, 90 mg q12hr, or 90 mg q6-8hr as necessary to normalize serum calcium levels
Secondary Hyperparathyroidism
Indicated for secondary HPT in patients with chronic kidney disease (CKD) on dialysis
Initial dose: 30 mg PO qDay
May increase if needed by titrating at 2-4 week intervals through sequential doses of 60, 90, 120, or 180 mg qDay
Parathyroid Carcinoma
Indicated to treat hypercalcemia in patients with parathyroid carcinoma
Initial dose: 30 mg PO q12hr
May increase if needed at 2-4 week intervals through sequential doses 60 mg q12hr, 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
Dosing Considerations
Monitor for hypocalcemia once maintenance dose established
Parathyroid carcinoma or primary hyperparathyroidism
- Monitor serum calcium every 2 months
Hyperparathyroidism in patients with CKD on dialysis
- Monitor serum calcium monthly
- For calcium levels between 7.5-8.4 mg/dL or if hypocalcemia symptoms occur, may administer calcium-containing phosphate binders and/or vitamin D sterols to raise serum calcium
- If calcium levels <7.5 mg/dL or hypocalcemia symptoms persist and the dose of vitamin D cannot be increased, withhold therapy until calcium levels reach 8 mg/dL and/or hypocalcemia symptom resolve, then reinitiate using next lowest dose
Safety and efficacy not established
Secondary Hyperparathyroidism (Orphan)
Orphan designation for treatment of secondary hyperparathyroidism (HPT) in pediatric patients with chronic kidney disease receiving dialysis
Sponsor
- Amgen, Inc; One Amgen Center Drive; Bldg 17, 1A-4-4, Mail Stop 17-1-B; Thousand Oaks, California 91320
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>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
Warnings
Contraindications
Hypersensitivity
Should not be initiated in severe hypocalcemia (serum Ca <lower limit of normal)
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 & Lactation
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.
Pharmacology
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%)
Administration
Oral Administration
Take with food or shortly after meal
Swallow tablet whole, do not chew, crush, or divide
Images
Patient Handout
Formulary
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