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 (dialysis-dependent chronic kidney disease):
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.
Hypocalcemia (patients with secondary hyperparathyroidism):
If corrected serum calcium ≥7.5 mg/dL but <8.4 mg/dL (>1.87 mmol/L but <2.1 mmol/L): Mild (eg, serum calcium 8 to <8.4 mg/dL [2 to <2.1 mmol/L]) or asymptomatic hypocalcemia due to calcimimetic may not require treatment. In patients with more significant or symptomatic hypocalcemia, may consider decreasing or temporarily discontinuing etelcalcetide or use of calcium-containing phosphate binders, vitamin D analogs, and/or adjustment of dialysate calcium content to raise calcium levels while avoiding hypercalcemia (Floege 2018; KDIGO 2017; manufacturer's labeling). If the etelcalcetide dose is stopped, reinitiate at a lower dose when the PTH is within the target range and hypocalcemia has been corrected.
If corrected serum calcium <7.5 mg/dL (<1.87 mmol/L) or if hypocalcemia symptoms persist despite treatment: Withhold etelcalcetide (and address any other predisposing factors for hypocalcemia) until corrected serum calcium ≥8 mg/dL (≥2 mmol/L) and/or symptoms of hypocalcemia resolve. Reinitiate etelcalcetide at a dose 5 mg lower than the last administered dose. If the last administered dose was 2.5 or 5 mg, reinitiate 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).
Refer to adult dosing.
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.
• 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. 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 risk.
• 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.
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
Solution (Parsabiv Intravenous)
2.5 mg/0.5 mL (per 0.5 mL): $117.97
5 mg/mL (per mL): $235.94
10 mg/2 mL (per mL): $235.95
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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.
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
Encorafenib: 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
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 (eg, muscle spasms, myalgia, paresthesia, seizure, tetany); worsening signs/symptoms of heart failure. In patients with seizure disorders, closely monitor albumin-corrected serum calcium levels. In patients at risk for GI bleeding (eg, gastritis, esophagitis, ulcers, severe vomiting), monitor for worsening of nausea and vomiting and for signs/symptoms of GI bleeding and ulceration. In patients at risk for QT prolongation and/or ventricular arrhythmia, closely monitor albumin-corrected serum calcium levels and QT interval.
Monitor albumin-corrected serum calcium levels at baseline and 1 week after initiation or dosage adjustment; after maintenance dose is established, monitor every 4 weeks. Monitor parathyroid hormone levels at baseline and 4 weeks after initiation or dosage adjustment and periodically thereafter.
Note: Due to the complexity and interdependency of the laboratory parameters used for therapeutic decisions in patients with chronic kidney disease-mineral and bone disorder, serial assessments of serum phosphate, calcium, and parathyroid hormone (PTH) levels should be considered together (KDIGO 2017).
Calcium (total): Adults: Normal range: 8.5 to 10.5 mg/dL (2.12 to 2.62 mmol/L) (IOM 2011). Avoid hypercalcemia for chronic kidney disease (CKD) stages G3a to G5D (KDIGO 2017).
Phosphorus: Normal range: 2.5 to 4.5 mg/dL (0.81 to 1.45 mmol/L). Lower elevated phosphorus levels toward the normal range for CKD stages G3a to G5D (KDIGO 2017).
PTH:
CKD stage G3a to G5: Optimal PTH level is unknown; evaluate patients with progressively elevated PTH levels or if levels are consistently above the normal range (assay-dependent) (KDIGO 2017).
Dialysis patients: Maintain PTH levels within 2 to 9 times the ULN for the assay used (KDIGO 2017).
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:
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.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟