(e tel KAL se tide)
- AMG 416
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)
Brand Names: U.S.
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).
Vss: ~796 L
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).
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.
Onset of Action
Decreased PTH levels: Within 30 minutes.
Time to Peak
Serum PKT: Time to steady state, plasma: CKD patients: 7 to 8 weeks.
CKD patients on hemodialysis: 3 to 4 days.
Healthy patients: 18.4 to 20 hours (Subramanian 2017).
Use: Labeled Indications
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).
Hypersensitivity to etelcalcetide or any component of the formulation.
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.
Refer to adult dosing.
Dosing: Renal Impairment
There are no dosage adjustments provided in the manufacturer’s labeling.
Dosing: Hepatic Impairment
There are no dosage adjustments provided in the manufacturer’s labeling.
Dosing: Adjustment for Toxicity
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).
Administer as an undiluted IV bolus into venous line of the dialysis circuit at the end of hemodialysis during or after rinse back. Do not mix or dilute prior to administration.
Store intact vials in refrigerator at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Once removed from refrigerator, use within 7 days (if stored in original carton) or within 4 hours (if removed from original carton). Do not expose to temperatures >25°C (77°F) or expose to direct sunlight if removed from original container.
Cinacalcet: May enhance the hypocalcemic effect of Etelcalcetide. Avoid combination
Endocrine & metabolic: Decreased serum calcium (≤79%), hypophosphatemia (1% to 18%)
Gastrointestinal: Diarrhea (11%), nausea (11%)
Neuromuscular & skeletal: Muscle spasm (12%)
1% to 10%:
Cardiovascular: Prolonged Q-T interval on ECG (1% to 5%), cardiac failure (2%)
Central nervous system: Headache (8%), paresthesia (6%)
Endocrine & metabolic: Hypocalcemia (serum calcium <7 m/dL: 8%), hyperkalemia (4%)
Gastrointestinal: Vomiting (9%)
Immunologic: Antibody development (7%; 80% of these patients have preexisting anti-etelcalcetid antibodies)
Neuromuscular & skeletal: Myalgia (2%)
<1% (Limited to important or life-threatening): Cardiac insufficiency, hypotension
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.
• 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.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
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.
Adverse events were observed in animal reproduction studies at doses which also caused maternal toxicity (including hypocalcemia).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience diarrhea or headache. Have patient report immediately to prescriber signs of low calcium (muscle cramps or spasms, numbness and tingling, or seizures); abnormal heartbeat; severe dizziness; passing out; severe nausea; vomiting; severe abdominal pain; black, tarry, or bloody stools; vomiting blood, or signs of heart problems (cough or shortness of breath that is new or worse, swelling of the ankles or legs, abnormal heartbeat, weight gain of more than five pounds in 24 hours, dizziness, or passing out) (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.