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6 X 0.5 ml
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The recommended initial dose of etelcalcetide is 5 mg administered by bolus injection 3 times per week. Corrected serum calcium should be at or above the lower limit of the normal range prior to administration of first dose of Etelcalcetide, a dose increase, or reinitiation after a dose stop (see also dose adjustments based on serum calcium levels). Etelcalcetide should not be administered more frequently than 3 times per week.
Dose titration: Etelcalcetide should be titrated so that doses are individualized between 2.5 mg and 15 mg. The dose may be increased in 2.5 mg or 5 mg increments no more frequently than every 4 weeks to a maximum dose of 15 mg 3 times per week to achieve the desired parathyroid hormone (PTH) target.
Dose adjustments based on PTH levels: PTH should be measured after 4 weeks from initiation or dose adjustment of Etelcalcetide , and approximately every 1-3 months during maintenance. Dose adjustment may be necessary at any time during treatment including the maintenance phase.
If PTH is below 100 pg/mL (10.6 pmol/L), the dose should be reduced or temporarily stopped. If PTH does not return to > 100 pg/mL following dose reduction, the dose should be stopped. For patients in whom the dose is stopped, Parsabiv should be reinitiated at a lower dose once PTH returns to > 150 pg/mL (15.9 pmol/L) and pre-dialysis serum corrected calcium (cCa) ≥ 8.3 mg/dL (2.08 mmol/L). If the patient’s last administered dose was 2.5 mg, Parsabiv may be reinitiated at the 2.5 mg dose level if PTH is > 300 pg/mL (31.8 pmol/L), and the most recent pre-dialysis serum cCa ≥ 8.3 mg/dL (2.08 mmol/L).
Additional recommendations related to the management of low calcium are provided in table 1 at the attached doctor’s leaflet.
Parsabiv may be used as part of a therapeutic regimen including phosphate binders and/or vitamin D sterols, as appropriate.
Missed doses: If a regularly scheduled hemodialysis treatment is missed, do not administer any missed doses. Parsabiv should be administered at the next hemodialysis treatment at the same dose. If doses are missed for more than 2 weeks, then Parsabiv should be administered at 5 mg, (or 2.5 mg if that was the patient’s last administered dose), and titrated to achieve the desired PTH.
Dose adjustments based on serum calcium levels: Serum calcium should be measured within 1 week of initiation or dose adjustment of Parsabiv. Once the maintenance phase has been established for a patient, corrected serum calcium should be measured approximately every 4 weeks. In the studies total serum calcium was measured using Roche modular analyzers. The lower limit of the normal range for corrected serum calcium was 8.3 mg/dL (2.08 mmol/L). Other laboratory assays may have different cut-offs for the lower limit of the normal range.
In the event that clinically meaningful decreases in corrected serum calcium levels below the lower limit of the normal range occur and/or symptoms of hypocalcemia occur, the following management in table 1 at the attached doctor’s leaflet is recommended.
Switch from cinacalcet to Parsabiv: Parsabiv should not be initiated in patients until 7 days after the last dose of cinacalcet and the corrected serum calcium is at or above the lower limit of the normal range.
Pediatric population: The safety and efficacy of etelcalcetide in children and adolescents less than 18 years has not yet been established. No data are available.
Elderly: Dosing recommendations for elderly patients are the same as for adult patients.
Method of administration: Parsabiv should not be diluted.
Parenteral medicinal products should be inspected visually for particulate matter and change in color prior to administration.
Parsabiv is administered into the venous line of the dialysis circuit at the end of the hemodialysis treatment during rinse-back or intravenously after rinse-back. When given during rinse-back at least 150 mL of rinse-back volume should be administered after injection. If rinse-back is completed and Parsabiv was not administered, then it may be administered intravenously followed by at least 10 mL saline flush volume.
Treatment of secondary hyperparathyroidism (SHPT) in adult patients with chronic kidney disease (CKD) on hemodialysis therapy.
Hypersensitivity to the active substance or to any of the excipients.
Patients with level of the calcium less than the lower limit of the normal range.
Hypocalcemia: The treatment should not be initiated in patients if the corrected serum calcium is less than the lower limit of the normal range.
Potential manifestations of hypocalcemia include paresthesias, myalgias, muscle spasm and seizures.
Since etelcalcetide lowers serum calcium, patients should be advised to seek medical attention if they experience symptoms of hypocalcemia and should be monitored for the occurrence of hypocalcemia. Serum calcium levels should be measured prior to initiating treatment, within 1 week of initiation or dose adjustment of Etelcalcetide and every 4 weeks during treatment. If clinically meaningful decreases in corrected serum calcium levels occur, steps should be taken to increase serum calcium levels.
Ventricular arrhythmia and QT prolongation secondary to hypocalcemia: Decreases in serum calcium can prolong the QT interval, potentially resulting in ventricular arrhythmia. Serum calcium levels should be closely monitored in patients with congenital long QT syndrome, previous history of QT prolongation, family history of long QT syndrome or sudden cardiac death and other conditions that predispose to QT prolongation and ventricular arrhythmia while being treated with Etelcalcetide.
ECG test should be performed before and during treatment, according to clinical judgment.
Convulsions: Cases of seizures have been reported in patients treated with Etelcalcetide.
The threshold for seizures may be lowered by significant reductions in serum calcium levels. Serum calcium levels should be closely monitored in patients with a history of a convulsion disorder while being treated with Etelcalcetide.
Worsening heart failure: Decreased myocardial performance, hypotension, and congestive heart failure (CHF) may be associated with significant reductions in serum calcium levels. Serum calcium levels should be monitored in patients with a history of congestive heart failure while being treated with Etelcalcetide, which may be associated with reductions in serum calcium levels.
Co-administration with other medicinal products: Administer Etelcalcetide with caution in patients receiving any other medicinal products known to lower serum calcium. Closely monitor serum calcium. Patients receiving Etelcalcetide should not be given cinacalcet. Concurrent administration may result in severe hypocalcemia.
Adynamic bone: Adynamic bone may develop if PTH levels are chronically suppressed below 100 pg/mL. 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, therapy can be resumed at a lower dose to maintain PTH in the target range.
Immunogenicity: In clinical studies, 7.1% of patients with SHPT treated with Parsabiv for up to 6 months tested positive for binding antibodies. 80.3% of these had pre-existing 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 antibodies with a clinically significant effect is suspected, contact the Marketing Authorization Holder to discuss antibody testing. Contact details are provided in section 8 of this leaflet.
Upper gastrointestinal bleeding: In clinical studies, two patients treated with Parsabiv in 1,253 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 Parsabiv.
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 Parsabiv treatment. Monitor patients for worsening of common GI adverse reactions of nausea and vomiting associated with Parsabiv and for signs and symptoms of GI bleeding and ulcerations during Parsabiv therapy. Promptly evaluate and treat any suspected GI bleeding.
Excipient with known effect: Parsabiv contains less than 1 mmol sodium per vial, that is to say essentially sodium-free.
Very common side effects with Parsabiv are blood calcium decreased, muscle spasms, diarrhea, nausea, and vomiting. They were mild to moderate in severity and transient in nature in the majority of patients. Discontinuation of therapy as a result of undesirable effects was mainly due to low blood calcium, nausea, and vomiting.
See prescribing information for full details.
No interaction studies have been performed. There is no known risk of pharmacokinetic interaction with etelcalcetide.
In vitro, etelcalcetide did not inhibit or induce CYP450 enzymes and was itself not a substrate for metabolism by CYP450 enzymes. In vitro, etelcalcetide was not a substrate of efflux and uptake transporter proteins; and etelcalcetide was not an inhibitor of common transporter proteins.
Concurrent administration of other medicinal products known to reduce serum calcium and Parsabiv may result in an increased risk of hypocalcemia. Patients receiving Parsabiv should not be given cinacalcet.
Pregnancy and Lactation
Pregnancy: There are no or limited amount of data from the use of etelcalcetide in pregnant women. As a precautionary measure, it is preferable to avoid the use of Parsabiv during pregnancy.
Lactation: It is unknown whether etelcalcetide is present in human milk. A risk to breastfed newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or discontinue/abstain from Parsabiv therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
See prescribing information for full details.
Overdose of etelcalcetide may lead to hypocalcemia with or without clinical symptoms and may require treatment. In the event of overdose, serum calcium should be checked and patients should be monitored for symptoms of hypocalcemia and appropriate measures should be taken. Although etelcalcetide is cleared by dialysis, hemodialysis has not been studied as a treatment for overdose. Single doses up to 60 mg and multiple doses up to 22.5 mg 3 times a week at the end of dialysis in patients receiving hemodialysis were safely administered in clinical trials.
Storage: Store in a refrigerator (2°C – 8°C). Store in the original carton in order to protect from light.
Compatibility: This medicinal product must not be mixed with other medicinal products.