PARSABIV SIDE EFFECTS
The following adverse reactions are discussed in greater detail in other sections of the labeling:
- Worsening Heart Failure
- Upper Gastrointestinal Bleeding
- Adynamic Bone
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 1: Adverse Reactions Reported in ≥ 5% of PARSABIV-Treated Patients
(N = 513)
(N = 503)
|Blood calcium decreaseda||10%||64%|
|* Included adverse reactions reported with at least 1% greater incidence in the PARSABIV group compared to the placebo group a 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)
b Symptomatic reductions in corrected serum calcium < 8.3 mg/Dl
c Paresthesia includes preferred terms of paresthesia and hypoesthesia
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
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.
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 patient incidence of maximum post-baseline predialysis QTcF > 500 msec in the placebo and PARSABIV groups was 1.9% and 4.8%, respectively.
In the combined placebo-controlled studies, the subject incidence of adverse reactions potentially related to hypersensitivity was 4.4% in the PARSABIV group and 3.7% in the placebo group. Hypersensitivity reactions in the PARSABIV group were pruritic rash, urticaria, and face edema.
As with all peptide therapeutics, there is potential for immunogenicity. The detection of anti-drug binding antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to etelcalcetide with the incidence of antibodies to other products may be misleading.
In clinical studies, 7.1% (71 out of 995) of patients with secondary hyperparathyroidism treated with PARSABIV for up to 6 months tested positive for binding anti-etelcalcetide antibodies. Fifty-seven out of 71 had pre-existing anti-etelcalcetide antibodies. No evidence of altered pharmacokinetic profile, clinical response, or safety profile was associated with pre-existing or developing anti-etelcalcetide antibodies.
The following adverse reactions have been identified during postmarketing use of PARSABIV. Because postmarketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Anaphylactic reaction
- Hypocalcemia in patients who were administered etelcalcetide concomitantly with other products known to lower serum calcium (e.g. cinacalcet, denosumab)
- Seizures secondary to hypocalcemia.
SRC: NLM .