Etelcalcetide

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# Overview
Etelcalcetide is a calcium-sensing receptor agonist that is FDA approved for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis.   Common adverse reactions include blood calcium decreased, muscle spasms, diarrhea, nausea, vomiting, headache, hypocalcemia, and paresthesia.

# Adult Indications and Dosage

## FDA-Labeled Indications and Dosage (Adult)
- Etelcalcetide is indicated for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis.
- Ensure corrected serum calcium is at or above the lower limit of normal prior to Etelcalcetide initiation, a Etelcalcetide dose increase, or re-initiation of Etelcalcetide therapy after a dosing interruption.
- The recommended starting dose of Etelcalcetide is 5 mg administered by intravenous (IV) bolus injection three times per week at the end of hemodialysis treatment.
- The maintenance dose of Etelcalcetide is individualized and determined by titration based on parathyroid hormone (PTH) and corrected serum calcium response. The maintenance dose is the dose that maintains PTH levels within the recommended target range and corrected serum calcium within the normal range. The lowest maintenance dose of Etelcalcetide is 2.5 mg three times per week, and the highest maintenance dose of Etelcalcetide is 15 mg three times per week.
- Administer Etelcalcetide only at the end of hemodialysis treatment.
- If a regularly scheduled hemodialysis treatment is missed, DO NOT administer any missed doses. Resume Etelcalcetide at the end of the next hemodialysis treatment at the prescribed dose. If doses of Etelcalcetide are missed for more than 2 weeks, re-initiate Etelcalcetide at the recommended starting dose of 5 mg (or 2.5 mg if that was the patients last dose).

## Off-Label Use and Dosage (Adult)

### Guideline-Supported Use
There is limited information regarding Etelcalcetide Off-Label Guideline-Supported Use and Dosage (Adult) in the drug label.

### NonGuideline-Supported Use
There is limited information regarding Etelcalcetide Off-Label Non-Guideline-Supported Use and Dosage (Adult) in the drug label.

# Pediatric Indications and Dosage

## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Etelcalcetide FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

## Off-Label Use and Dosage (Pediatric)

### Guideline-Supported Use
There is limited information regarding Etelcalcetide Off-Label Guideline-Supported Use and Dosage (Pediatric) in the drug label.

### NonGuideline-Supported Use
There is limited information regarding Etelcalcetide Off-Label Non-Guideline-Supported Use and Dosage (Pediatric) in the drug label.

# Contraindications
- Etelcalcetide is contraindicated in patients with known hypersensitivity to Etelcalcetide or any of its excipients. Hypersensitivity reactions, including pruritic rash, urticaria, and face edema, have occurred with Etelcalcetide.

# Warnings
- Etelcalcetide lowers serum calcium and can lead to hypocalcemia, sometimes severe. Significant lowering of serum calcium can cause paresthesias, myalgias, muscle spasms, seizures, QT interval prolongation, and ventricular arrhythmia.
QT Interval Prolongation and Ventricular Arrhythmia
- In the combined placebo-controlled studies, more patients treated with Etelcalcetide experienced a maximum increase from baseline of greater than 60 msec in the QTcF interval (0% placebo versus 1.2% Etelcalcetide). In these studies, the incidence of a maximum post-baseline predialysis QTcF > 500 msec in the placebo and Etelcalcetide groups was 1.9% and 4.8%, respectively. 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 due to Etelcalcetide. Closely monitor corrected serum calcium and QT interval in patients at risk receiving Etelcalcetide.
Seizures
- Significant reductions in corrected serum calcium may lower the threshold for seizures. Patients with a history of seizure disorder may be at increased risk for seizures if they develop hypocalcemia due to Etelcalcetide. Monitor corrected serum calcium in patients with seizure disorders receiving Etelcalcetide.
- Concurrent administration of Etelcalcetide with another oral calcium-sensing receptor agonist could result in severe, life-threatening hypocalcemia. Patients switching from cinacalcet to Etelcalcetide should discontinue cinacalcet for at least 7 days prior to initiating Etelcalcetide. Closely monitor corrected serum calcium in patients receiving Etelcalcetide and concomitant therapies known to lower serum calcium.
- Measure corrected serum calcium prior to initiation of Etelcalcetide. Do not initiate in patients if the corrected serum calcium is less than the lower limit of normal. Monitor corrected serum calcium within 1 week after initiation or dose adjustment and every 4 weeks during treatment with Etelcalcetide. Educate patients on the symptoms of hypocalcemia, and advise them to contact a healthcare provider if they occur.
- If corrected serum calcium falls below the lower limit of normal or symptoms of hypocalcemia develop, start or increase calcium supplementation (including calcium, calcium-containing phosphate binders, and/or vitamin D sterols or increases in dialysate calcium concentration). Etelcalcetide dose reduction or discontinuation of Etelcalcetide may be necessary.
- In clinical studies with Etelcalcetide, cases of hypotension, congestive heart failure, and decreased myocardial performance have been reported. In clinical studies, heart failure requiring hospitalization occurred in 2% of Etelcalcetide-treated patients and 1% of placebo-treated patients. Reductions in corrected serum calcium may be associated with congestive heart failure, however, a causal relationship to Etelcalcetide could not be completely excluded. Closely monitor patients treated with Etelcalcetide for worsening signs and symptoms of heart failure.
- In clinical studies, two patients treated with Etelcalcetide in 1253 patient-years of exposure had upper gastrointestinal (GI) bleeding noted at the time of death while no patient in the control groups in 384 patient-years of exposure had upper GI bleeding noted at the time of death. The exact cause of GI bleeding in these patients is unknown, and there were too few cases to determine whether these cases were related to Etelcalcetide.
- 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 while receiving Etelcalcetide treatment. Monitor patients for worsening of common GI adverse reactions of nausea and vomiting associated with Etelcalcetide and for signs and symptoms of GI bleeding and ulcerations during Etelcalcetide therapy. Promptly evaluate and treat any suspected GI bleeding.
- Adynamic bone may develop if PTH levels are chronically suppressed. If PTH levels decrease below the recommended target range, the dose of vitamin D sterols and/or Etelcalcetide should be reduced or therapy discontinued. After discontinuation, resume therapy at a lower dose to maintain PTH levels in the target range.

# Adverse Reactions

## Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
- The data in Table 2 are derived from two placebo-controlled clinical studies in patients with chronic kidney disease and secondary hyperparathyroidism on hemodialysis. The data reflect exposure of 503 patients to Etelcalcetide with a mean duration of exposure to Etelcalcetide of 23.6 weeks. The mean age of patients was approximately 58 years, and 60% of the patients were male. Of the total patients, 67% were Caucasian, 28% were Black or African American, 2.6% were Asian, 1.2% were Native Hawaiian or Other Pacific Islander, and 1.6% were categorized as Other.
- Table 2 shows common adverse reactions associated with the use of Etelcalcetide in the pool of placebo-controlled studies. These adverse reactions occurred more commonly on Etelcalcetide than on placebo and were reported in at least 5% of patients treated with Etelcalcetide.
- Other adverse reactions associated with the use of Etelcalcetide but reported in < 5% of patients in the Etelcalcetide group in the two placebo-controlled clinical studies were:
- Hyperkalemia: 3% and 4% for placebo and Etelcalcetide, respectively.
- Hospitalization for Heart Failure: 1% and 2% for placebo and Etelcalcetide, respectively.
- Myalgia: 0.2% and 2% for placebo and Etelcalcetide, respectively.
- Hypophosphatemia: 0.2% and 1% for placebo and Etelcalcetide, respectively.
Description of Selected Adverse Reactions
Hypocalcemia
- In the combined placebo-controlled studies, a higher proportion of patients on Etelcalcetide developed at least one corrected serum calcium value below 7.0 mg/dL (7.6% Etelcalcetide, 3.1% placebo), below 7.5 mg/dL (27% Etelcalcetide, 5.5% placebo), and below 8.3 mg/dL (79% Etelcalcetide, 19% placebo). In the combined placebo-controlled studies, 1% of patients in the Etelcalcetide group and 0% of patients in the placebo group discontinued treatment due to an adverse reaction attributed to a low corrected serum calcium.
Hypophosphatemia
- In the combined placebo-controlled studies, 18% of patients treated with Etelcalcetide and 8.2% of patients treated with placebo had at least one measured phosphorus level below the lower normal limit (i.e., 2.2 mg/dL).
QTc Interval Prolongation Secondary to Hypocalcemia
- In the combined placebo-controlled studies, more patients treated with Etelcalcetide experienced a maximum increase from baseline of greater than 60 msec in the QTcF interval (0% placebo versus 1.2% Etelcalcetide). The patient incidence of maximum post-baseline predialysis QTcF > 500 msec in the placebo and Etelcalcetide groups was 1.9% and 4.8%, respectively.
Hypersensitivity
- In the combined placebo-controlled studies, the subject incidence of adverse reactions potentially related to hypersensitivity was 4.4% in the Etelcalcetide group and 3.7% in the placebo group. Hypersensitivity reactions in the Etelcalcetide group were pruritic rash, urticaria, and face edema.
- As with all peptide therapeutics, there is potential for immunogenicity. The detection of anti-drug binding antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Etelcalcetide with the incidence of antibodies to other products may be misleading.
- In clinical studies, 7.1% (71 out of 995) of patients with secondary hyperparathyroidism treated with Etelcalcetide for up to 6 months tested positive for binding anti-Etelcalcetide antibodies. Fifty-seven out of 71 had pre-existing anti-Etelcalcetide antibodies.
- No evidence of altered pharmacokinetic profile, clinical response, or safety profile was associated with pre-existing or developing anti-Etelcalcetide antibodies. If formation of anti-Etelcalcetide binding antibodies with a clinically significant effect is suspected, contact Amgen at 1-800-77-AMGEN (1-800-772-6436) to discuss antibody testing.

## Postmarketing Experience
There is limited information regarding Etelcalcetide Postmarketing Experience in the drug label.

# Drug Interactions
There is limited information regarding Etelcalcetide Drug Interactions in the drug label.

# Use in Specific Populations

### Pregnancy
Pregnancy Category (FDA): 
Risk Summary
- There are no available data on the use of Etelcalcetide in pregnant women. In animal reproduction studies, effects were seen at doses associated with maternal toxicity that included hypocalcemia. In a pre- and post-natal study in rats administered Etelcalcetide during organogenesis through delivery and weaning, there was a slight increase in perinatal pup mortality, delay in parturition, and transient effects on pup growth at exposures 1.8 times the human exposure for the clinical dose of 15 mg three times per week. There was no effect on sexual maturation, neurobehavioral, or reproductive function in the rat offspring. In embryo-fetal studies, when rats and rabbits were administered Etelcalcetide during organogenesis, reduced fetal growth was observed at exposures 2.7 and 7 times exposures for the clinical dose, respectively.
- The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Data (Animal)
- There were no effects on embryo-fetal development in Sprague-Dawley rats when Etelcalcetide was dosed at 0.75, 1.5, and 3 mg/kg/day by the intravenous route during organogenesis (pre-mating to gestation day 17) at exposures up to 1.8 times human exposures at the clinical dose of 15 mg three times per week based on AUC. No effects on embryo-fetal development were observed in New Zealand White rabbits at doses of Etelcalcetide of 0.375, 0.75, and 1.5 mg/kg by the intravenous route (gestation day 7 to 19), representing up to 4.3 times human exposures based on AUC. In separate studies at higher doses of 4.5 mg/kg in rats (gestation days 6 to 17) and 2.25 mg/kg in rabbits (gestation days 7 to 20), representing 2.7- and 7-fold clinical exposures, respectively, there was reduced fetal growth associated with maternal toxicities of hypocalcemia, tremoring, and reductions in body weight and food consumption.
- In a pre- and post-natal development study in Sprague-Dawley rats administered Etelcalcetide at 0.75, 1.5, and 3 mg/kg/day by the intravenous route (gestation day 7 to lactation day 20), there was a slight increase in perinatal pup mortality, delay in parturition, and transient reductions in post-natal growth at 3 mg/kg/day (representing 1.8-fold human exposures at the clinical dose of 15 mg three times per week based on AUC), associated with maternal toxicities of hypocalcemia, tremoring, and reductions in body weight and food consumption. There were no effects on sexual maturation, neurobehavioral, or reproductive function at up to 3 mg/kg/day, representing exposures up to 1.8-fold human exposure based on AUC.
Pregnancy Category (AUS): 
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Etelcalcetide in women who are pregnant.

### Labor and Delivery
There is no FDA guidance on use of Etelcalcetide during labor and delivery.

### Nursing Mothers
Risk Summary
- There are no data regarding the presence of Etelcalcetide in human milk or effects on the breastfed infant or on milk production. Studies in rats showed -Etelcalcetide was present in the milk at concentrations similar to plasma. Because of the potential for Etelcalcetide to cause adverse effects in breastfed infants including hypocalcemia, advise women that use of Etelcalcetide is not recommended while breastfeeding.
Data
- Presence in milk was assessed following a single intravenous dose of -Etelcalcetide in lactating rats at maternal exposures similar to the exposure at the human clinical dose of 15 mg three times per week. -Etelcalcetide-derived radioactivity was present in milk at levels similar to plasma.

### Pediatric Use
- The safety and efficacy of Etelcalcetide have not been established in pediatric patients.

### Geriatic Use
- Of the 503 patients in placebo-controlled studies who received Etelcalcetide, 177 patients (35.2%) were  65 years old and 72 patients (14%) were  75 years old. No clinically significant differences in safety or efficacy were observed between patients  65 years and younger patients ( 18 and < 65 years old). No differences in plasma concentrations of Etelcalcetide were observed between patients  65 years and younger patients ( 18 and < 65 years old).

### Gender
There is no FDA guidance on the use of Etelcalcetide with respect to specific gender populations.

### Race
There is no FDA guidance on the use of Etelcalcetide with respect to specific racial populations.

### Renal Impairment
There is no FDA guidance on the use of Etelcalcetide in patients with renal impairment.

### Hepatic Impairment
There is no FDA guidance on the use of Etelcalcetide in patients with hepatic impairment.

### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Etelcalcetide in women of reproductive potentials and males.

### Immunocompromised Patients
There is no FDA guidance one the use of Etelcalcetide in patients who are immunocompromised.

# Administration and Monitoring

### Administration
- Do not mix or dilute Etelcalcetide prior to administration. The solution is clear and colorless. Inspect Etelcalcetide for particulate matter and discoloration prior to administration. Do not use Etelcalcetide vials if particulate matter or discoloration is observed.
- Administer Etelcalcetide by intravenous bolus injection into the venous line of the dialysis circuit at the end of the hemodialysis treatment during rinse back or intravenously after rinse back.

### Monitoring
- Corrected serum calcium: Prior to initiation or reinitiation, 1 week after dosage initiation or adjustment, and every 4 weeks during maintenance.
- Parathyroid hormone: At 4 weeks after dosage initiation or adjustment and per protocol during maintenance.
- QT interval: Patients at risk for QT prolongation and ventricular arrhythmias.
- Signs and symptoms of hypocalcemia.
- Signs and symptoms of worsening heart failure.
- Worsening nausea and vomiting associated with therapy.
- Signs and symptoms of gastrointestinal bleeding or ulceration: Especially in at-risk patients.

# IV Compatibility
There is limited information regarding the compatibility of Etelcalcetide and IV administrations.

# Overdosage
- There is no clinical experience with Etelcalcetide overdosage. Overdosage of Etelcalcetide may lead to hypocalcemia with or without clinical symptoms and may require treatment. Although Etelcalcetide is cleared by dialysis, hemodialysis has not been studied as a treatment for Etelcalcetide overdosage. In the event of overdosage, corrected serum calcium should be checked and patients should be monitored for symptoms of hypocalcemia, and appropriate measures should be taken.

# Pharmacology

## Mechanism of Action
- Etelcalcetide is a calcimimetic agent that allosterically modulates the calcium-sensing receptor (CaSR). Etelcalcetide binds to the CaSR and enhances activation of the receptor by extracellular calcium. Activation of the CaSR on parathyroid chief cells decreases PTH secretion.

## Structure

## Pharmacodynamics
- Following a single intravenous bolus administration of Etelcalcetide, PTH levels decreased within 30 minutes post-dose. In the single-dose study, the extent and duration of the reduction in PTH increased with increasing dose. Reduction in PTH levels correlated with plasma Etelcalcetide concentrations in hemodialysis patients. The reduction in PTH resulted in reductions in calcium and attenuation of post-dialytic phosphate elevation. The effect of reducing PTH levels was maintained throughout the 6-month dosing period when Etelcalcetide was administered by intravenous bolus three times a week.

## Pharmacokinetics
- The pharmacokinetics of Etelcalcetide is linear and does not change over time following single (5 to 60 mg) and multiple intravenous doses (2.5 to 20 mg) in chronic kidney disease patients with secondary hyperparathyroidism requiring hemodialysis. Etelcalcetide exhibited tri-exponential decay following intravenous administration. Based on population pharmacokinetic analysis, following three times a week intravenous dosing at the end of each 3- to 6-hour hemodialysis session in chronic kidney disease patients, Etelcalcetide plasma levels reached steady state in 7-8 weeks after dosing with a predicted accumulation ratio of 3- to 4-fold, and the effective half-life was 3 to 4 days.
Distribution
- In the population pharmacokinetics model, volume of distribution at steady state (Vss) was approximately 796 L. Etelcalcetide is predominately bound to plasma albumin by reversible covalent binding. Non-covalent binding of Etelcalcetide to plasma proteins is low with a fraction unbound ratio of 0.53. The ratio of blood-to-plasma -Etelcalcetide concentrations is approximately 0.6.
Elimination
Metabolism
- Etelcalcetide is not metabolized by CYP450 enzymes. Etelcalcetide is biotransformed in blood by reversible disulfide exchange with endogenous thiols to predominantly form conjugates with serum albumin.
- Following a single radiolabeled dose of Etelcalcetide in chronic kidney disease patients with secondary hyperparathyroidism requiring hemodialysis, the plasma exposure of biotransformation products is approximately 5-fold higher than that of Etelcalcetide and their concentration-time course parallels that of Etelcalcetide.
Excretion
- Etelcalcetide is cleared by renal excretion in patients with normal renal function, while hemodialysis is the predominant elimination pathway in chronic kidney disease patients requiring hemodialysis. In chronic kidney disease patients on hemodialysis, Etelcalcetide was removed with a hemodialysis clearance value of 7.66 L/hr. Following a single radiolabeled dose of Etelcalcetide in chronic kidney disease patients with secondary hyperparathyroidism requiring hemodialysis, approximately 60% of -Etelcalcetide was recovered in dialysate, and approximately 7% recovered in urine and feces combined over 175 days of collection period.
Specific Populations
Effects of Body Weight, Gender, Race, and Age
- Results of population pharmacokinetic analyses indicate that body weight (29 to 163 kg), gender, race, and age (20 to 93 years of age) do not influence the pharmacokinetics of Etelcalcetide. The pharmacokinetics of Etelcalcetide in patients  65 years of age and in patients < 65 years of age is similar.
Drug Interactions
In Vitro Assessment of Drug Interactions
- Etelcalcetide did not inhibit or induce CYP450 enzymes, and is not a substrate of CYP450 enzymes. Etelcalcetide was not a substrate of efflux and uptake transporter proteins (P-glycoprotein , breast cancer resistance protein , organic anion transporter  1 and 3, organic anion polypeptide transporter  1B1 and 1B3, organic cation transporter  2, and peptide transporter  1 and 2). Etelcalcetide was also not an inhibitor of common transporter proteins (Pgp, BCRP, OAT1, OAT3, OATP1B1, OATP1B3, OCT2, or bile salt export pump ).

## Nonclinical Toxicology
- No drug-related tumors were observed in Tg rasH2 transgenic mice when Etelcalcetide was administered at doses of 0.3, 1, and 3 mg/kg in females and 0.375, 0.75, and 1.5 mg/kg in males once daily for 26 weeks by the subcutaneous route, representing up to 0.4-fold clinical exposure at the maximum human dose of 15 mg three times per week based on AUC. Etelcalcetide administration did not produce drug-related tumors when Sprague-Dawley rats were dosed at 0.2, 0.4, 0.8, and 1.6 mg/kg/day by the subcutaneous route for 89 weeks in females and 92 weeks in males, representing up to 0.4-fold clinical exposures achieved in patients receiving Etelcalcetide at 15 mg three times per week, based on AUC.
- Etelcalcetide was mutagenic in some strains of bacteria (Ames), but was not genotoxic in two in vitro and two in vivo mammalian genotoxicity assays. Therefore, Etelcalcetide is considered non-genotoxic in humans.
- There was no effect on male or female fertility when Etelcalcetide was dosed at 0.75, 1.5, and 3 mg/kg/day by the intravenous route to rats at exposure levels up to 1.8-fold higher than exposures achieved in patients receiving Etelcalcetide at 15 mg three times per week based on AUC.

# Clinical Studies
- The efficacy and safety of Etelcalcetide for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease receiving hemodialysis three times per week were evaluated in two 26-week, randomized, double-blind, placebo-controlled studies (Study 1 and Study 2).
- The starting dose of Etelcalcetide was 5 mg three times per week administered at the end of hemodialysis. Etelcalcetide dose was titrated every 4 weeks until week 17 to a maximum dose of 15 mg three times per week to target a PTH level of less than or equal to 300 pg/mL. Etelcalcetide was suspended temporarily if two consecutive PTH levels were less than 100 pg/mL. The dose of Etelcalcetide was not increased if PTH levels were less than or equal to 300 pg/mL, corrected serum calcium was less than 8.3 mg/dL, symptomatic hypocalcemia occurred, or the investigator judged that no dose increase was needed.
- The average dose of Etelcalcetide at the time of the efficacy assessment (weeks 20 through 27, inclusive) was 7.2 mg three times per week. Patients with lower screening PTH levels were on lower doses with a mean average dose of 5.7 mg, 7.4 mg, and 8.7 mg three times per week for patients with screening PTH levels less than 600 pg/mL, 600 to less than or equal to 1000 pg/mL, and greater than 1000 pg/mL, respectively. Throughout the study, patients were maintained on a dialysate calcium concentration of greater than or equal to 2.25 meq/L.
- In each study, the primary outcome measure was the proportion of patients with a greater than 30% reduction in PTH levels from baseline to the efficacy assessment phase (mean PTH levels for weeks 20 through 27, inclusive). The other outcome measures were the proportion of patients with a mean PTH of less than or equal to 300 pg/mL, percent change from baseline in PTH, corrected serum calcium, and phosphate levels.
- Study 1 enrolled 508 patients (254 Etelcalcetide, 254 placebo). Baseline demographic and disease characteristics were balanced between groups. The mean age of the patients was 58 years, and 57% were male. Of enrolled patients, 69% were White, 28% were Black, 2% were Asian, and 13% were Hispanic/Latino in ethnicity. The mean baseline PTH level was 834.2 pg/mL, the mean baseline corrected serum calcium was 9.6 mg/dL, and the average duration of hemodialysis prior to study entry (minimum to maximum) was 5.5 (0.1 to 32.2) years. Sixty-six percent of patients had a mean screening PTH level greater than or equal to 600 pg/mL, 74% patients were receiving vitamin D sterols, and 84% patients were receiving phosphate binders.
- Study 2 enrolled 515 patients (255 Etelcalcetide, 260 placebo). Baseline demographic and disease characteristics were balanced between groups. The mean age of the patients was 59 years, and 64% were male. Of enrolled patients, 65% were White, 28% were Black, 4% were Asian, and 13% were Hispanic/Latino in ethnicity. The mean baseline PTH level was 848.4 pg/mL, the mean baseline corrected serum calcium was 9.7 mg/dL, and the average duration of hemodialysis prior to study entry (minimum to maximum) was 5.4 (0.3 to 32.1) years. Sixty-seven percent of patients had a mean screening PTH level greater than or equal to 600 pg/mL, 62% patients were receiving vitamin D sterols, and 81% patients were receiving phosphate binders.
- In both studies, a significantly higher proportion of patients treated with Etelcalcetide achieved a greater than 30% reduction in PTH levels from baseline to the efficacy assessment phase (mean PTH levels for weeks 20 through 27, inclusive) than the proportion of patients treated with placebo. In both studies, reduction in mean PTH, corrected serum calcium, and serum phosphate levels from baseline to the end of study were observed in the Etelcalcetide arm, and differences between Etelcalcetide and placebo were statistically significant. Results for each individual study are shown in Table 3.
- Etelcalcetide decreased PTH levels regardless of baseline PTH, duration of dialysis, whether or not patients had been previously treated with cinacalcet, and whether or not patients were receiving vitamin D sterols. Reductions in PTH levels, corrected serum calcium, and serum phosphate were maintained for up to 78 weeks of treatment in those patients who elected to participate in the extension phase of both studies.

# How Supplied
- Etelcalcetide (Etelcalcetide) injection is supplied in a single-dose vial (type I glass) with stopper (fluoropolymer laminated elastomeric) and an aluminum seal with flip-off dust cover containing 5 mg/mL of Etelcalcetide as a ready-to-use clear and colorless solution in the following strengths:

## Storage
- Store in the original carton in refrigerator at 2C to 8C (36F to 46F) to protect from light. Once removed from the refrigerator:
- Do not expose to temperatures above 25C (77F).
- Use within 7 days if stored in the original carton.
- Use within 4 hours and do not expose to direct sunlight if removed from the original carton.

# Images

## Drug Images

## Package and Label Display Panel

# Patient Counseling Information
Hypocalcemia
- Advise patients to report symptoms of hypocalcemia, including paresthesias, myalgias, muscle spasms, and seizures, to their healthcare provider.
Heart Failure
- Advise patients with heart failure that use of Etelcalcetide may worsen their heart failure and additional monitoring may be required.
Upper Gastrointestinal Bleeding
- Advise patients to report any symptoms of upper gastrointestinal bleeding to their healthcare provider.
Laboratory Monitoring
- Inform patients of the importance of regular blood tests, in order to monitor the safety and efficacy of Etelcalcetide therapy.
Lactation
- Advise women that use of Etelcalcetide is not recommended while breastfeeding.

# Precautions with Alcohol
Alcohol-Etelcalcetide interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

# Brand Names
- Parsabiv

# Look-Alike Drug Names
There is limited information regarding Etelcalcetide Look-Alike Drug Names in the drug label.

# Drug Shortage Status
Drug Shortage

# Price