Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Hypocalcemia
Etelcalcetide treatment should not be initiated in patients if the corrected serum calcium is less than the lower limit of the normal range (see section 4.3).

Potential manifestations of hypocalcemia include paresthesias, myalgias, muscle spasms 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 (see section 4.2). 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 (see section 4.2).



Ventricular arrhythmia and QT prolongation secondary to hypocalcemia 
Decreases in serum calcium can prolong the QT interval, potentially resulting in ventricular arrhythmia (see section 4.8). 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 (see section 4.8). 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 CHF while being treated with etelcalcetide (see section 4.2), 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 (see section 4.5).

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 (see section 4.2).

Immunogenicity

In clinical studies, 7.1% of patients with SHPT treated with etelcalcetide 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.

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
This medicinal product contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially 'sodium-free'.

Effects on Driving

4.7    Effects on ability to drive and use machines

Parsabiv has no or negligible influence on the ability to drive and use machines. However, certain potential manifestations of hypocalcemia may affect the ability to drive and use machines (see sections 4.4 and 4.8).