Note: Ensure corrected serum calcium is at or above the lower limit of normal prior to initiation, a dose increase, or re-initiation of therapy after a dosing interruption.
Hyperparathyroidism, secondary (chronic kidney disease patients on hemodialysis): IV: Initial: 5 mg IV bolus 3 times per week at the end of hemodialysis.
Dosage adjustments: Titrate dose in 2.5 mg or 5 mg increments not more frequently than every 4 weeks to a dose that maintains PTH levels within recommended target range and corrected serum calcium within the normal range; maximum maintenance dose: 15 mg three times per week; minimum maintenance dose: 2.5 mg three times per week.
Conversion from cinacalcet: Discontinue cinacalcet for at least 7 days prior to initiating etelcalcetide.
Missed dose : If hemodialysis is missed, do not administer. Resume etelcalcetide at the end of the next hemodialysis treatment. If doses are missed for >2 weeks, re-initiate with 5 mg (or 2.5 mg if that was the patient's last dose) 3 times per week.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary.
There are no dosage adjustments provided in the manufacturer’s labeling.
Refer to adult dosing.
Corrected serum calcium below the lower limit of normal but ≥7.5 mg/dL (without symptoms of hypocalcemia): Consider decreasing dose or temporarily discontinuing or using concomitant therapies to increase corrected serum calcium. If the dose is stopped, re-initiate at a lower dose when the PTH is within the target range and hypocalcemia has been corrected.
Hypocalcemia: Stop therapy and treat hypocalcemia if the corrected serum calcium <7.5 mg/dL or hypocalcemia is symptomatic. When the corrected serum calcium is within normal limits, symptoms of hypocalcemia have resolved, and predisposing factors for hypocalcemia have been addressed, re-initiate at a dose 5 mg lower than the last administered dose. If the last administered dose was 2.5 mg or 5 mg, re-initiate at a dose of 2.5 mg.
PTH levels below the target range: Decrease dose or temporarily discontinue therapy. Re-initiate at a lower dose when PTH is within target range (and if corrected serum calcium is at or above the lower limit of normal).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Parsabiv: 5 mg/mL (1 mL); 10 mg/2 mL (2 mL); 2.5 mg/0.5 mL (0.5 mL)
No
IV: Administer as an undiluted IV bolus into venous line of the dialysis circuit after hemodialysis during rinse back or IV after rinse back. If administered during rinse back, administer a sufficient volume (eg, 150 mL of rinse back) after etelcalcetide injection into the dialysis tubing. If administered after rinse back, follow IV administration with ≥10 mL saline flush. Do not mix or dilute prior to administration. Must be administered after blood is no longer circulating through the dialyzer.
Hyperparathyroidism, secondary: Treatment of secondary hyperparathyroidism (HPT) in adults with chronic kidney disease (CKD) on hemodialysis.
Limitations of use: Not recommended in adults with parathyroid carcinoma, primary hyperparathyroidism, or with CKD not on hemodialysis (has not been studied).
Etelcalcetide may be confused with ecallantide.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Endocrine & metabolic: Hypocalcemia (≤79%; serum calcium <7 m/dL: 8%), hypophosphatemia (1% to 18%)
Gastrointestinal: Diarrhea (11%), nausea (11%)
Neuromuscular & skeletal: Muscle spasm (12%)
1% to 10%:
Cardiovascular: Prolonged QT interval on ECG (1% to 5%), cardiac failure (2%)
Central nervous system: Headache (8%), paresthesia (6%)
Endocrine & metabolic: Hyperkalemia (4%)
Gastrointestinal: Vomiting (9%)
Hypersensitivity: Hypersensitivity reaction (4%)
Immunologic: Antibody development (7%)
Neuromuscular & skeletal: Myalgia (2%)
<1%, postmarketing, and/or case reports: Anaphylaxis, cardiac insufficiency, hypotension
Hypersensitivity to etelcalcetide or any component of the formulation.
Concerns related to adverse effects:
• Adynamic bone disease: May develop if parathyroid hormone levels are chronically suppressed; reduce dose or discontinue etelcalcetide and/or vitamin D if parathyroid hormone levels decrease below the recommended target range.
• Cardiovascular effects: QT prolongation and ventricular arrhythmia secondary to hypocalcemia may occur. 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. Closely monitor corrected serum calcium and QT interval. Cases of hypotension, heart failure, and decreased myocardial performance have also been reported; may correlate with decreases in corrected serum calcium although a causal relationship to etelcalcetide cannot be excluded. Closely monitor for signs and symptoms of worsening heart failure during therapy.
• GI effects: Upper GI bleeding has been reported; relationship to etelcalcetide uncertain. Patients with risk factors for upper GI bleeding (eg, gastritis, esophagitis, ulcers, severe vomiting) may be at increased. Monitor patients for worsening of nausea and vomiting associated with etelcalcetide and for signs/symptoms of GI bleeding and ulcerations during therapy.
• Hypocalcemia: Severe and potentially life-threatening events associated with hypocalcemia (eg, muscle spasms, myalgias, paresthesias, seizures, QT interval prolongation, ventricular arrhythmia) may occur. Hypocalcemia may require treatment interruption, dose reduction, or initiation (or dose increases) of calcium-based phosphate binder and/or vitamin D to raise serum calcium depending on calcium levels or symptoms of hypocalcemia. Do not initiate therapy if the corrected serum calcium is less than the lower limit of normal; corrected serum calcium must be at or above the lower limit of normal prior to initiation, dose increase or re-initiation.
Disease-related concerns:
• Heart failure: Patients with heart failure may experience worsening of their heart failure with use; additional monitoring may be required.
• Seizure disorder: Use with caution in patients with a history of seizure disorder; seizure threshold is lowered by significant decreases in serum calcium. Monitor corrected serum calcium levels closely.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy
Azithromycin (Systemic): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Azithromycin (Systemic). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Carbetocin: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Carbetocin. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Chloroquine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Chloroquine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Cinacalcet: May enhance the hypocalcemic effect of Etelcalcetide. Risk X: Avoid combination
Clofazimine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Clofazimine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Dabrafenib: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Dabrafenib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Denosumab: May enhance the hypocalcemic effect of Calcimimetic Agents. Risk C: Monitor therapy
Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Fexinidazole: May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Fluorouracil Products: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Gadobenate Dimeglumine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Gadobenate Dimeglumine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Halofantrine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Halofantrine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Haloperidol: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Inotuzumab Ozogamicin: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Inotuzumab Ozogamicin. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Levoketoconazole: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Levoketoconazole. Risk X: Avoid combination
Lofexidine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Lofexidine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Midostaurin: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Midostaurin. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Ondansetron: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Oxytocin: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Oxytocin. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Pentamidine (Systemic): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Piperaquine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Piperaquine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Probucol: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Probucol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): Etelcalcetide may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Antidepressants (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Antipsychotics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Class IC Antiarrhythmics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-Prolonging Inhalational Anesthetics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Kinase Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Miscellaneous Agents (Moderate Risk): May enhance the QTc-prolonging effect of Etelcalcetide. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Quinolone Antibiotics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Quinolone Antibiotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Siponimod: Calcimimetic Agents may increase the serum concentration of Siponimod. Management: Coadministration of siponimod with drugs which are both moderate inhibitors of CYP2C9 and moderate or strong inhibitors of CYP3A4 is not recommended. Risk D: Consider therapy modification
Toremifene: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Toremifene. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Adverse events were observed in animal reproduction studies at doses which also caused maternal toxicity (including hypocalcemia).
It is not known if etelcalcetide is present in breast milk. Due to the potential for hypocalcemia in a breastfeeding infant, breastfeeding is not recommended by the manufacturer.
Signs/symptoms of hypocalcemia, worsening of heart failure, GI bleeding/ulcerations; QT interval in patients at risk for QT interval prolongation and ventricular arrhythmia.
Corrected serum calcium and PTH levels, per the following recommendations:
Corrected serum calcium levels: Prior to initiation and 1 week after dose initiation or adjustment. After the maintenance dose is established, monitor every 4 weeks.
PTH levels: Prior to initiation and 4 weeks after dose initiation or adjustment. After the maintenance dose is established, monitor per clinical practice.
Target goals of PTH, calcium, and phosphorus in adult CKD patients on hemodialysis (ie, CKD stage 5), per clinical practice guidelines:
Corrected serum calcium: CKD stage 5: 8.4 to 9.5 mg/dL (2.1 to 2.37 mmol/L) (K/DOQI 2003)
Serum phosphorus: 3.5 to 5.5 mg/dL (K/DOQI 2003)
Serum calcium-phosphorus product: CKD Stage 5: <55 mg2/dL2 (K/DOQI 2003)
Intact PTH: CKD Stage 5: 150 to 300 pg/mL (K/DOQI 2003)
Etelcalcetide, a synthetic peptide calcimimetic, allosterically activates the calcium-sensing receptor (CaSR) on the parathyroid gland, resulting in decreased PTH secretion, and serum calcium and phosphorus levels in patients with secondary hyperparathyroidism on hemodialysis (Alexander 2015).
Onset of action: Decreased PTH levels: Within 30 minutes.
Distribution: Vss: ~796 L
Metabolism: Undergoes biotransformation in blood by reversible disulfide exchange with endogenous thiols to predominantly form conjugates with serum albumin; majority of these biotransformed moieties circulating in plasma exist as serum albumin peptide conjugates (SAPC) (Subramanian 2017).
Half-life elimination:
CKD patients on hemodialysis: 3 to 4 days.
Healthy patients: 18.4 to 20 hours (Subramanian 2017).
Time to peak, serum PKT:
Time to steady state, plasma: CKD patients: 7 to 8 weeks.
Excretion:
CKD patients on hemodialysis: Dialysate (~60% of administered dose; ~89% of recovered dose); urine (3.2% of administered dose) and feces (4.5% of administered dose) (Subramanian 2017).
Healthy patients: Urine.
Solution (Parsabiv Intravenous)
2.5 mg/0.5 mL (per 0.5 mL): $106.09
5 mg/mL (per mL): $212.19
10 mg/2 mL (per mL): $212.19
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