Etelcalcetide
FDA Drug Information • Also known as: Parsabiv
- Brand Names
- Parsabiv
- Route
- INTRAVENOUS
- Dosage Form
- INJECTION, SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION PARSABIV (etelcalcetide) is a synthetic peptide calcium-sensing receptor agonist. Etelcalcetide is a white to off-white powder with a molecular formula of C 38 H 73 N 21 O 10 S 2 ∙xHCl (4 ≤ x ≤ 5) and a molecular weight of 1047.5 g/mol (monoisotopic; free base). It is soluble in water. The hydrochloride salt of etelcalcetide is described chemically as N-acetyl-D-cysteinyl-S-(L-cysteine disulfide)-D-alanyl-D-arginyl-D-arginyl-D-arginyl-D-alanyl-D-argininamide hydrochloride. PARSABIV (etelcalcetide) injection is supplied in a single-dose vial containing 5 mg/mL of etelcalcetide as a sterile, preservative-free, ready-to-use clear and colorless solution for intravenous injection. Each PARSABIV single-dose vial contains 2.5 mg etelcalcetide (equivalent to 2.88 mg etelcalcetide as hydrochloride salt) or 5 mg etelcalcetide (equivalent to 5.77 mg etelcalcetide as hydrochloride salt) or 10 mg etelcalcetide (equivalent to 11.54 mg etelcalcetide as hydrochloride salt). PARSABIV single-dose vial is formulated with 0.85% (w/v) sodium chloride, 10 mM succinic acid, and adjusted to pH 3.3 with sodium hydroxide and/or hydrochloric acid. Chemical Structure
What Is Etelcalcetide Used For?
1 INDICATIONS AND USAGE PARSABIV is indicated for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis. PARSABIV is a calcium-sensing receptor agonist indicated for: Secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis. ( 1 ) Limitations of Use: PARSABIV has not been studied in adult patients with parathyroid carcinoma, primary hyperparathyroidism, or with CKD who are not on hemodialysis and is not recommended for use in these populations. Limitations of Use: PARSABIV has not been studied in adult patients with parathyroid carcinoma, primary hyperparathyroidism, or with chronic kidney disease who are not on hemodialysis and is not recommended for use in these populations .
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Ensure corrected serum calcium is at or above the lower limit of normal prior to initiation, dose increase, or re-initiation. ( 2.1 ) The recommended starting dose is 5 mg administered by intravenous bolus injection three times per week at the end of hemodialysis treatment. ( 2.1 ) The maintenance dose is individualized and determined by titration based on parathyroid hormone (PTH) and corrected serum calcium response. The dose range is 2.5 to 15 mg three times per week. ( 2.1 ) The dose may be increased in 2.5 mg or 5 mg increments no more frequently than every 4 weeks. ( 2.2 ) Measure serum calcium within 1 week after initiation or dose adjustment and every 4 weeks for maintenance. ( 2.2 ) Measure PTH after 4 weeks from initiation or dose adjustment. ( 2.2 ) Decrease or temporarily discontinue PARSABIV in individuals with PTH levels below the target range. ( 2.2 ) Consider decreasing or temporarily discontinuing PARSABIV or use concomitant therapies to increase corrected serum calcium in patients with a corrected serum calcium below the lower limit of normal but at or above 7.5 mg/dL without symptoms of hypocalcemia. ( 2.2 ) Stop PARSABIV and treat hypocalcemia if the corrected serum calcium falls below 7.5 mg/dL or patients report symptoms of hypocalcemia. ( 2.2 ) Do not mix or dilute prior to administration. ( 2.3 ) Administer by intravenous bolus injection into the venous line of the dialysis circuit after hemodialysis, during rinse back or intravenously after rinse back. Administer a sufficient volume of saline, e.g. 150 mL of rinse back, after injection into the dialysis tubing. If administered after rinse back, administer PARSABIV intravenously followed by at least 10 mL of saline flush. ( 2.3 ) 2.1 Recommended Dosing Ensure corrected serum calcium is at or above the lower limit of normal prior to PARSABIV initiation, a PARSABIV dose increase, or re-initiation of PARSABIV therapy after a dosing interruption [see Dosage and Administration (2.2) and Warnings and Precautions (5.1) ] . The recommended starting dose of PARSABIV is 5 mg administered by intravenous (IV) bolus injection three times per week at the end of hemodialysis treatment [see Dosage and Administration (2.3) ] . The maintenance dose of PARSABIV is individualized and determined by titration based on parathyroid hormone (PTH) and corrected serum calcium response [see Dosage and Administration (2.2) ] . 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 PARSABIV is 2.5 mg three times per week, and the highest maintenance dose of PARSABIV is 15 mg three times per week . Administer PARSABIV only at the end of hemodialysis treatment. If a regularly scheduled hemodialysis treatment is missed, DO NOT administer any missed doses. Resume PARSABIV at the end of the next hemodialysis treatment at the prescribed dose. If doses of...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Hypocalcemia [see Warnings and Precautions (5.1) ] Worsening Heart Failure [see Warnings and Precautions (5.2) ] Upper Gastrointestinal Bleeding [see Warnings and Precautions (5.3) ] Adynamic Bone [see Warnings and Precautions (5.4) ] The most common adverse reactions (≥ 5%) were blood calcium decreased, muscle spasms, diarrhea, nausea, vomiting, headache, hypocalcemia, and paresthesia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Amgen Inc. at 1-800-77-AMGEN (1-800-772-6436) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 PARSABIV with a mean duration of exposure to PARSABIV 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 PARSABIV in the pool of placebo-controlled studies. These adverse reactions occurred more commonly on PARSABIV than on placebo and were reported in at least 5% of patients treated with PARSABIV. Table 2: Adverse Reactions Reported in ≥ 5% of PARSABIV-Treated Patients Adverse Reaction Included adverse reactions reported with at least 1% greater incidence in the PARSABIV group compared to the placebo group Placebo (N = 513) PARSABIV (N = 503) Blood calcium decreased Asymptomatic reductions in calcium below 7.5 mg/dL or clinically significant asymptomatic reductions in corrected serum calcium between 7.5 and < 8.3 mg/dL (that required medical management) 10% 64% Muscle spasms 7% 12% Diarrhea 9% 11% Nausea 6% 11% Vomiting 5% 9% Headache 6% 8% Hypocalcemia Symptomatic reductions in corrected serum calcium < 8.3 mg/dL 0.2% 7% Paresthesia Paresthesia includes preferred terms of paresthesia and hypoesthesia 1% 6% Other adverse reactions associated with the use of PARSABIV but reported in < 5% of patients in the PARSABIV group in the two placebo-controlled clinical studies were: Hyperkalemia: 3% and 4% for placebo and PARSABIV, respectively. Hospitalization for Heart Failure: 1% and 2% for placebo and PARSABIV, respectively. Myalgia: 0.2% and 2% for placebo and PARSABIV, respectively. Hypophosphatemia: 0.2% and 1% for placebo and PARSABIV, respectively. Description of Selected Adverse Reactions Hypocalcemia In the combined placebo-controlled studies, a higher proportion of patients on PARSABIV developed at least one corrected serum calcium value below 7.0 mg/dL (7.6% PARSABIV, 3.1% placebo), below 7.5 mg/dL (27% PARSABIV, 5.5% placebo), and below 8.3 mg/dL (79% PARSABIV, 19% placebo). In the combined placebo-controlled studies, 1% of patients in the PARSABIV 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 PARSABIV 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 PARSABIV experienced a maximum increase from baseline of greater than 60 msec in the QTcF interval (0% placebo versus 1.2% PARSABIV). The...
Contraindications
4 CONTRAINDICATIONS PARSABIV is contraindicated in patients with known hypersensitivity to etelcalcetide or any of its excipients. ( 4 ) Hypersensitivity PARSABIV is contraindicated in patients with known hypersensitivity to etelcalcetide or any of its excipients. Hypersensitivity reactions, including face edema and anaphylactic reaction, have occurred with PARSABIV [see Adverse Reactions (6) ] .
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are no available data on the use of PARSABIV 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 Data 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...
Overdosage
10 OVERDOSAGE There is no clinical experience with PARSABIV overdosage. Overdosage of PARSABIV may lead to hypocalcemia with or without clinical symptoms and may require treatment. Although PARSABIV is cleared by dialysis, hemodialysis has not been studied as a treatment for PARSABIV 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 [see Warnings and Precautions (5.1) ] .
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING PARSABIV (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: 2.5 mg/0.5 mL Carton of 10 single-dose vials NDC 55513-740-10 NDC 55513-740-20 5 mg/mL Carton of 10 single-dose vials NDC 55513-741-10 NDC 55513-741-20 10 mg/2 mL Carton of 10 single-dose vials NDC 55513-742-10 NDC 55513-742-20 Storage Store in the original carton in refrigerator at 2°C to 8°C (36°F to 46°F) to protect from light. Once removed from the refrigerator: Do not expose to temperatures above 25°C (77°F). 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.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.