Adverse Reactions of Cinacalcet in CKD Patients on Dialysis
Cinacalcet commonly causes gastrointestinal adverse effects and hypocalcemia, which may adversely affect nutrition and quality of life, with approximately 150 per 1,000 patients experiencing nausea and 60 per 1,000 developing hypocalcemia when treated for one year. 1
Most Common Adverse Reactions
Gastrointestinal Effects
The most frequent adverse reactions are gastrointestinal in nature and occur at substantially higher rates than placebo:
- Nausea: Occurs in 27-31% of patients (RR 2.05), representing approximately 150 cases per 1,000 patients treated annually 2, 1, 3
- Vomiting: Affects 25-27% of patients (RR 1.95) 2, 3
- Diarrhea: Occurs in 20-21% of patients (RR 1.15) 2, 3
- Decreased appetite/Anorexia: Affects 6-7% of patients 3
These gastrointestinal effects are usually mild to moderate in severity and transient, but severe or prolonged cases can lead to dehydration and worsening hypercalcemia, requiring careful electrolyte monitoring. 3, 4
Metabolic Complications
Hypocalcemia is the most significant metabolic adverse effect:
- Risk increase: 7.38-fold higher than placebo (RR 7.38,95% CI 5.43-10.03) 2, 1
- Incidence: Approximately 11% of patients in long-term studies 3
- Clinical significance: Requires close monitoring of serum calcium levels 3
The FDA label specifically warns about hypocalcemia and recommends monitoring calcium levels closely, particularly when initiating therapy or adjusting doses. 3
Other Common Adverse Effects
Additional adverse reactions occurring in ≥5% of patients include:
- Muscle spasms: 11.1% of patients 3
- Dizziness: 7-10% of patients 3
- Myalgia: 15% of patients 3
- Asthenia/Fatigue: 5-7% of patients 3
- Headache: 11.5% of patients 3
- Dyspepsia: 7.4% of patients 3
Serious Adverse Reactions
Cardiovascular Effects
Isolated, idiosyncratic cases of hypotension, worsening heart failure, and/or arrhythmias have been reported in postmarketing surveillance, particularly in patients with impaired cardiac function, potentially mediated by reductions in serum calcium levels. 3
Upper Gastrointestinal Bleeding
The FDA warns about potential upper GI bleeding and ulcerations during cinacalcet therapy, requiring prompt evaluation if suspected. 3
Seizures
Seizure incidence is low but present:
- 1.4% in cinacalcet-treated patients versus 0.7% in placebo patients across completed trials 3
- 2.5% versus 1.6% in long-term studies 3
Adynamic Bone Disease
May develop if iPTH levels are suppressed below 100 pg/mL, with 11% of patients having mean iPTH values below this threshold during treatment. 3
Critical Clinical Context
The adverse gastrointestinal effects may adversely influence nutrition and quality of life in dialysis patients, which is particularly concerning given that cinacalcet provides no reductions in mortality. 2 On average, treating 1,000 people with CKD stage 5D with cinacalcet for one year prevents only about 3 patients from requiring parathyroidectomy while causing 60 cases of hypocalcemia and 150 cases of nausea. 1
Monitoring Requirements
To minimize adverse reactions:
- Serum calcium monitoring: Essential to detect hypocalcemia early 3
- iPTH monitoring: Reduce dose if iPTH falls below 150 pg/mL to prevent adynamic bone disease 3
- GI symptom assessment: Monitor for signs of GI bleeding, particularly in patients with risk factors 3
- Electrolyte monitoring: Especially important in patients with severe nausea/vomiting to prevent dehydration 3
Common Pitfalls
The most important caveat is that while these adverse effects are common and may significantly impact quality of life, cinacalcet has little or no effect on all-cause mortality (RR 0.97) and uncertain effects on cardiovascular mortality. 2 Therefore, routine use is not warranted, and benefits are primarily limited to preventing parathyroidectomy in patients for whom surgery is contraindicated. 2, 1