Cinacalcet Use in Calciphylaxis Patients
Yes, cinacalcet can be used in calciphylaxis patients and appears to reduce the incidence of calciphylaxis events, though it should be used as part of a multi-modal treatment approach with careful monitoring for hypocalcemia.
Evidence Supporting Cinacalcet Use in Calciphylaxis
Reduction in Calciphylaxis Incidence
- Cinacalcet significantly reduced calciphylaxis events in hemodialysis patients with secondary hyperparathyroidism (relative hazard 0.31; 95% CI 0.13-0.79; P=0.014), with only 6 patients on cinacalcet developing calciphylaxis compared to 18 on placebo in the EVOLVE trial 1
- The cumulative event rate at 4 years was 0.005% with cinacalcet versus 0.011% with placebo 1
Treatment Response Rates
- Overall response rate (partial or complete) to cinacalcet-containing regimens was 83.4% for monotherapy and 82.8% for combination therapy 2
- Complete response rates were higher with combination therapy (62.1%) versus monotherapy (41.7%) 2
- Rapid reduction in intact parathyroid hormone occurred over 2-33 months in both treatment groups 2
Clinical Case Evidence
- Multiple case reports demonstrate successful treatment of calciphylaxis with cinacalcet, including complete ulcer healing within 2 months when combined with peritoneal dialysis and phosphate binders 3
- Multi-modal treatment with IV sodium thiosulfate, cinacalcet, and sevelamer achieved 100% one-year survival and 80% two-year survival in five hemodialysis patients with calciphylaxis 4
Critical Safety Considerations
Hypocalcemia Risk
- Cinacalcet increases hypocalcemia risk 7-fold (RR 7.38), which is particularly dangerous as hypocalcemia can prolong QT interval, lower seizure threshold, and cause hypotension, worsening heart failure, and/or arrhythmias 5, 6, 7
- Life-threatening events and fatal outcomes from hypocalcemia have been reported with cinacalcet 7
- Monitor serum calcium carefully and frequently during treatment 7
FDA-Approved Indications
- Cinacalcet is FDA-approved for secondary hyperparathyroidism in adult CKD patients on dialysis only 7
- Cinacalcet is NOT indicated for CKD patients not on dialysis 7
- Also approved for hypercalcemia in parathyroid carcinoma and primary hyperparathyroidism when parathyroidectomy is contraindicated 7
Gastrointestinal Side Effects
- Nausea (RR 2.05), vomiting (RR 1.95), and diarrhea (RR 1.15) are common adverse effects that may affect nutrition and quality of life 5, 6, 7
Recommended Treatment Approach
Optimal Regimen
- Use cinacalcet as part of combination therapy rather than monotherapy for better complete response rates (62.1% vs 41.7%) 2
- Combine with sodium thiosulfate IV and non-calcium-based phosphate binders (sevelamer) for optimal outcomes 4
- Use low-calcium dialysate (1.25-1.50 mmol/L) in dialysis patients 5
Dosing Strategy
- Start with 30 mg once daily for secondary hyperparathyroidism 7
- Titrate every 2-4 weeks through sequential doses of 30,60,90,120, and 180 mg once daily as needed 7
- Always take with food or shortly after a meal; tablets must be taken whole, never divided 7
Monitoring Requirements
- Measure serum calcium no earlier than 12 hours after the most recent dose 7
- Monitor calcium approximately monthly once maintenance dose is established 7
- Do not initiate cinacalcet if serum calcium is below the lower limit of normal 7
- Monitor for upper GI bleeding in at-risk patients 7
Important Caveats
Treatment Failure Recognition
- One case report documented calciphylaxis development despite cinacalcet treatment with normalized calcium and phosphorus levels, ultimately requiring parathyroidectomy 8
- Recurrence of calciphylaxis lesions occurred 3 months after cinacalcet discontinuation in one patient, requiring parathyroidectomy for definitive control 3
When to Consider Parathyroidectomy
- If calciphylaxis progresses despite optimal medical management including cinacalcet, proceed to parathyroidectomy 3, 8
- Parathyroidectomy should be considered for tertiary hypercalcemic hyperparathyroidism 5