Etelcalcetide is a medication used for the treatment of secondary hyperparathyroidism (SHPT) in adult patients with chronic kidney disease (CKD) on hemodialysis. It works by mimicking the action of calcium in the body and thereby reducing the secretion of parathyroid hormone (PTH) from the parathyroid gland. This helps in managing the elevated levels of PTH commonly seen in patients with CKD on dialysis.

The drug is administered intravenously during the hemodialysis session. It offers an alternative option for patients who may not respond well to other treatments for SHPT or who experience adverse effects with other medications.

Parsabiv (Etelcalcetide) is a calcimimetic peptide that reduces the serum parathyroid hormone levels along with calcium and phosphate.

Parsabiv (Etelcalcetide) Uses:

• It is used in the treatment of secondary hyperparathyroidism in adults with chronic kidney disease who are on hemodialysis.
• It is not recommended in elevated parathyroid hormone levels caused by:
  • Parathyroid carcinoma,
  • Primary hyperparathyroidism, or
  • Patients with CKD who are not on hemodialysis.

Parsabiv (Etelcalcetide) Dose in Adults

Note: Prior to the treatment initiation, dose-escalation, or reinitiation of the drug, the serum calcium should be above the lower limits of normal.

Parsabiv (Etelcalcetide) Dose in the treatment of secondary hyperparathyroidism (in patients with chronic kidney disease on hemodialysis)

Initial Dose:

• 5 mg given through a vein (IV) three times a week at the end of each dialysis session.

Adjusting the Dose:

• The dose can be adjusted gradually, usually every 4 weeks, by increasing or decreasing it by 2.5 mg or 5 mg.
• This adjustment aims to keep the parathyroid hormone (PTH) levels within the recommended range and maintain normal calcium levels in the blood.
• The highest dose to maintain is 15 mg three times a week, and the lowest is 2.5 mg three times a week.

Switching from Cinacalcet:

• If the patient was previously taking cinacalcet, they should stop it for at least 7 days before starting etelcalcetide.

Missed Doses:

• If a dialysis session is missed, do not give the etelcalcetide dose. Instead, resume it at the end of the next dialysis session.
• If doses are missed for more than 2 weeks, restart with the initial dose of 5 mg (or the last dose if it was 2.5 mg) three times a week.

Parsabiv (Etelcalcetide) use in Children:

The safety and efficacy of Etelcalcetide in children is not established.

Parsabiv (Etelcalcetide) Pregnancy Risk Factor: D 

• In animal studies, harmful effects on the babies were seen when pregnant animals were given doses that also made the mothers sick (causing low calcium levels).

Etelcalcetide use during breastfeeding:

• It's uncertain whether etelcalcetide passes into breast milk.
• Because there's a risk of low calcium levels in a nursing baby, the manufacturer advises against breastfeeding while using this medication.

Parsabiv (Etelcalcetide) Dose in Kidney Disease:

Dose adjustment in CKD is not necessary.

Parsabiv (Etelcalcetide) Dose in Liver disease:

The manufacturer's instructions don't include any specific dosage adjustments for people with liver problems.

Common Side Effects of Parsabiv (Etelcalcetide) Include:

• Endocrine & Metabolic:
  • Decreased Serum Calcium
  • Hypophosphatemia
• Gastrointestinal:
  • Diarrhea
  • Nausea
• Neuromuscular & Skeletal:
  • Muscle Spasm

Less Common Side Effects Of Parsabiv (Etelcalcetide):

• Cardiovascular:
  • Prolonged Q-T Interval On ECG
  • Cardiac Failure
• Central Nervous System:
  • Headache
  • Paresthesia
• Endocrine & Metabolic:
  • Hypocalcemia
  • Hyperkalemia
• Gastrointestinal:
  • Vomiting
• Immunologic:
  • Antibody Development
• Neuromuscular & Skeletal:
  • Myalgia

Contraindication of Parsabive(Etelcalcetide):

If someone has a known allergy or hypersensitivity to etelcalcetide or any ingredient in the medication, they should not use it.

Warnings and precautions

A dynamic bone disease

• Adynamic bone disease may occur if parathyroid hormone levels are persistently low due to treatment with etelcalcetide.
• If this happens, the dose of etelcalcetide or vitamin D may need to be reduced or stopped.
• It's important to monitor parathyroid hormone levels regularly and adjust treatment accordingly to maintain them within the recommended range.

Cardiovascular effects

• Etelcalcetide can potentially cause cardiovascular effects, including QT prolongation and ventricular arrhythmia, especially if there's a drop in blood calcium levels.
• Patients with conditions like congenital long QT syndrome, history of QT interval prolongation, or family history of sudden cardiac death may be at higher risk.
• Monitoring corrected serum calcium and QT interval closely is important.
• There have been reports of hypotension, heart failure, and decreased heart muscle function, which might be linked to decreased blood calcium levels, although a direct cause by etelcalcetide isn't certain.
• Monitoring for signs of worsening heart failure during treatment is essential.

Gastrointestinal effects:

• Some patients using etelcalcetide have reported upper gastrointestinal (GI) bleeding, although it's unclear if it's directly caused by the medication.
• Patients with factors that raise the risk of upper GI bleeding, like gastritis, esophagitis, ulcers, or severe vomiting, may be at higher risk.
• It's important to watch for worsening nausea and vomiting related to etelcalcetide and to be vigilant for signs or symptoms of GI bleeding and ulcers while on the therapy.

Hypocalcemia:

• Hypocalcemia, a condition of low calcium levels, can lead to severe and potentially life-threatening events, including muscle spasms, muscle pain, tingling sensations, seizures, QT interval prolongation, and abnormal heart rhythms.
• If hypocalcemia occurs, treatment may need to be paused, the dose reduced, or additional calcium-based phosphate binders and/or vitamin D supplements may be required to raise calcium levels.
• Therapy with etelcalcetide should not start if the corrected serum calcium is below the lower limit of normal.
• Before starting, increasing the dose, or restarting treatment, the corrected serum calcium level must be at or above the lower limit of normal.

Heart failure:

• Patients with heart failure may experience a worsening of their condition while using etelcalcetide.
• It's important to closely monitor these patients for any signs or symptoms of worsening heart failure during treatment.
• Additional monitoring may be necessary to ensure their safety.

Seizure disorder:

• Caution should be exercised when using etelcalcetide in patients with a history of seizure disorder.
• Significant decreases in serum calcium levels can lower the seizure threshold, potentially increasing the risk of seizures.
• Therefore, it's important to closely monitor corrected serum calcium levels in these patients to help prevent seizures.

Etelcalcetide: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitor:

Signs/Symptoms to Watch For:

• Hypocalcemia: Look out for muscle spasms, muscle pain, tingling sensations, seizures, and abnormal heart rhythms.
• Worsening Heart Failure: Keep an eye on any signs or symptoms indicating a worsening of heart failure.
• GI Bleeding/Ulcerations: Monitor for signs like nausea, vomiting, or blood in the stool that could suggest GI bleeding or ulcers.
• QT Interval: Pay attention to the QT interval, especially in patients at risk for QT interval prolongation and ventricular arrhythmia.

Monitoring Corrected Serum Calcium and PTH Levels:

• Corrected Serum Calcium Levels:
  • Before starting treatment and one week after starting or adjusting the dose.
  • Once the maintenance dose is set, check every four weeks.
• PTH Levels:
  • Before starting treatment and four weeks after starting or adjusting the dose.
  • After reaching the maintenance dose, follow monitoring practices based on clinical guidelines.

How to administer Parsabiv (Etelcalcetide)?

Method:

• Administer directly into the venous line of the dialysis circuit.

Timing:

• Give as an undiluted IV bolus after completion of hemodialysis, during the rinse back phase, or immediately after rinse back.

During Rinse Back:

• If given during rinse back, ensure a sufficient volume (e.g., 150 mL of rinse back solution) follows the etelcalcetide injection into the dialysis tubing.

After Rinse Back:

• If administered after rinse back, follow with a saline flush of at least 10 mL.

Do Not Dilute:

• Administer without mixing or dilution prior to administration.

Timing with Dialyzer:

• Ensure administration after blood is no longer circulating through the dialyzer to avoid interference with the dialysis process.

Mechanism of action of Parsabiv (Etelcalcetide):

• Etelcalcetide is a synthetic peptide calcimimetic medication that works by activating a receptor called the calcium-sensing receptor (CaSR) on the parathyroid gland.
• This activation leads to a decrease in the secretion of parathyroid hormone (PTH) and helps lower levels of calcium and phosphorus in the blood.
• It's used specifically in patients with secondary hyperparathyroidism who are undergoing hemodialysis.

Onset of Action:

• Decreased PTH levels: Within 30 minutes of administration.

Distribution:

• Volume of distribution (V): Approximately 796 liters.

Metabolism:

• Etelcalcetide undergoes biotransformation in the blood through reversible disulfide exchange with endogenous thiols. This process predominantly forms conjugates with serum albumin, with the majority of these biotransformed substances circulating in the plasma as serum albumin peptide conjugates (SAPC).

Half-life Elimination:

• CKD patients on hemodialysis: 3 to 4 days.
• Healthy patients: 18.4 to 20 hours.

Time to Peak, Serum PKT:

• Time to steady state, plasma: Approximately 7 to 8 weeks in CKD patients.

Excretion:

• CKD patients on hemodialysis: Etelcalcetide is primarily excreted through dialysate (~60% of administered dose), with a smaller amount excreted in urine (3.2% of administered dose) and feces (4.5% of administered dose).
• Healthy patients: Excretion occurs primarily through urine.

International Brands of Etelcalcetide (Parsabiv):

• Parsabiv

Etelcalcetide Brand Names in Pakistan:

Not available.