Etelcalcetide

Patients receiving Parsabiv should not be given cinacalcet. Concurrent administration may result in severe hypocalcaemia.

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.

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.

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.

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.

There are no or limited amount of data from the use of etelcalcetide in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of etelcalcetide during pregnancy.

It is unknown whether etelcalcetide is present in human milk. Available data in rats have shown that etelcalcetide is excreted in milk. A risk to breastfed newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or discontinue/abstain from etelcalcetide therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

No data are available on the effect of etelcalcetide on human fertility. Animal studies do not indicate direct or indirect harmful effects with respect to fertility.

Etelcalcetide has no or negligible influence on the ability to drive and use machines. However, certain potential manifestations of hypocalcaemia may affect the ability to drive and use machines.

Summary of safety profile

Very common side effects with etelcalcetide are blood calcium decreased, muscle spasms, diarrhoea, 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.

List of adverse reactions

Adverse reactions are listed below using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

Adverse reactions from controlled clinical studies and post-marketing experience:

Immune system disorders

Not known: Hypersensitivity reactions¹ (including anaphylaxis)

Metabolism and nutrition disorders

Very common: Blood calcium decreased^1,4

Common: Hypocalcaemia^1,5, Hyperkalaemia², Hypophosphataemia

Nervous system disorders

Common: Headache, Paraesthesia³

Uncommon: Convulsions

Cardiac disorders

Common: Worsening heart failure¹, QT prolongation¹

Vascular disorders

Common: Hypotension

Gastrointestinal disorders

Very common: Nausea, Vomiting, Diarrhoea

Musculoskeletal and connective tissue disorders

Very common: Muscle spasms

Common: Myalgia

¹ See section on description of selected adverse reactions.
² Hyperkalaemia includes preferred terms of hyperkalaemia and blood potassium increased.
³ Paraesthesia includes preferred terms of paraesthesia and hypoaesthesia.
⁴ Asymptomatic reductions in calcium below 7.5 mg/dL (1.88 mmol/L) or clinically significant asymptomatic reductions in serum cCa between 7.5 and <8.3 mg/dL (1.88 and <2.08 mmol/L) (that required medical management).
⁵ Symptomatic reductions in serum cCa <8.3 mg/dL (2.08 mmol/L).

Description of selected adverse reactions

Hypocalcaemia

Most events of asymptomatic blood calcium decreased and symptomatic hypocalcaemia were mild or moderate in severity. In the combined placebo-controlled studies, a higher proportion of patients in the etelcalcetide group compared with patients in the placebo group developed at least one serum cCa value <7.0 mg/dL (1.75 mmol/L) (7.6% etelcalcetide; 3.1% placebo), <7.5 mg/dL (1.88 mmol/L) (27.1% etelcalcetide; 5.5% placebo), and <8.3 mg/dL (2.08 mmol/L) (78.6% etelcalcetide; 19.4% placebo). In these studies 1% of patients in the etelcalcetide group and 0% of patients in the placebo group discontinued treatment due to the adverse event of low serum calcium.

QTc prolongation secondary to hypocalcaemia

In the combined placebo-controlled studies, a higher percentage of patients in the etelcalcetide group compared with the placebo group had a maximum increase from baseline of >60 msec in the QTcF interval (1.2% etelcalcetide; 0% placebo). The patient incidence of maximum post-baseline pre-dialysis QTcF >500 msec in the etelcalcetide and placebo groups was 4.8% and 1.9%, respectively.

Worsening heart failure

In the combined placebo-controlled studies, the subject incidence of adjudicated CHF events requiring hospitalisation was 2.2% in the etelcalcetide treatment group compared to 1.2% in the placebo group.