Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile
Very common adverse reactions with Parsabiv are blood calcium decreased (64%), vomiting (13%), muscle spasms (12%), diarrhea (11%) and nausea (11%). They were mild to moderate in severity and 

transient in nature in the majority of patients. Discontinuation of therapy as a result of adverse reactions was mainly due to low blood calcium, nausea, and vomiting.

Tabulated 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).

Table 1 Adverse reactions from controlled clinical studies and post-marketing experience 
MedDRA system organ class                Frequency category           Adverse reactions (SOC)
Immune system disorders                  Not known                    Hypersensitivity reactions (including anaphylaxis)
Metabolism and nutrition disorders       Very common                  Blood calcium decreased 1, 4 Common                       Hypocalcemia1, 5
Hyperkalemia2
Hypophosphatemia
Nervous system disorders                 Common                       Headache Paresthesia3
Uncommon                     Convulsions6
Cardiac disorders                        Common                       Worsening heart failure1 QT prolongation1
Vascular disorders                       Common                       Hypotension Gastrointestinal disorders               Very common                  Nausea Vomiting
Diarrhea
Uncommon                     Upper gastrointestinal bleeding
Musculoskeletal and connective           Very common                  Muscle spasms tissue disorders                         Common                       Myalgia 1
See section Description of selected adverse reactions.
2
Hyperkalemia includes preferred terms of hyperkalemia and blood potassium increased.
3
Paresthesia includes preferred terms of paresthesia and hypoesthesia.
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).
6
See section 4.4.

Description of selected adverse reactions

Hypocalcemia
Most events of asymptomatic blood calcium decreased and symptomatic hypocalcemia were mild or moderate in severity. In the combined placebo-controlled studies, a higher proportion of patients in the Parsabiv 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% Parsabiv; 3.1% placebo), < 7.5 mg/dL (1.88 mmol/L) (27.1% Parsabiv; 5.5% placebo), and < 8.3 mg/dL (2.08 mmol/L) (78.6% Parsabiv; 19.4% placebo). In these studies 1% of patients in the Parsabiv group and 0% of patients in the placebo group discontinued treatment due to the adverse event of low serum calcium. For further information regarding potential manifestations of hypocalcemia and serum calcium monitoring see sections 4.4 and 4.2 respectively.

QTc prolongation secondary to hypocalcemia

In the combined placebo-controlled studies, a higher percentage of patients in the Parsabiv group compared with the placebo group had a maximum increase from baseline of > 60 msec in the QTcF 
interval (1.2% Parsabiv; 0% placebo). The patient incidence of maximum post-baseline pre-dialysis QTcF > 500 msec in the Parsabiv 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 hospitalization was 2.2% in the Parsabiv treatment group compared to 1.2% in the placebo group.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il/