The FDA has not yet approved use of the calcimimetic cinacalcet in children receiving dialysis. In the absence of formal guidelines, the European Society for Paediatric Nephrology, Chronic Kidney Disease-Mineral and Bone Disorder and Dialysis Working Groups, and the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) have issued a joint position statement on pediatric use based on available evidence (2 randomized controlled trials, 9 interventional or observational studies, and case reports) and expert opinion.
In Nephrology Dialysis Transplantation, the authors discussed the following 22 recommendations on using cinacalcet in children on dialysis:
Before starting cinacalcet
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- Monitor serum calcium, phosphate, parathyroid hormone (PTH) and 25-hydroxyvitamin D levels regularly and make treatment decisions based on all of the trends.
2. Use albumin-corrected calcium levels (ionized calcium levels are more accurate).
3. Keep serum calcium and phosphate levels within age-appropriate normal range. Consider calcium intake from diet, medications, and dialysate.
Benefits and Contraindications
4. Use cinacalcet in children older than 3 years on dialysis who have persistent and severe hyperparathyroidism in the presence of high or high-normal calcium levels, despite optimized conventional management, including active vitamin D.
5. There is no clear threshold level of PTH above which cinacalcet therapy should be started.
6. Do not start cinacalcet in patients with albumin-corrected calcium levels less than 2.40 mmol/L.
7. Do not start cinacalcet in patients with prolonged QT interval.
8. Use cinacalcet with caution in patients with history of seizures, cardiac arrhythmia, significant liver disease or poor adherence to medications.
9. Use drugs that prolong the QTc interval or interact with cinacalcet with caution.
Treatment schedule
10. Use a starting dose of cinacalcet of 0.2 mg/kg/d or less based on dry weight rounded to the nearest whole dose unit.
11. If desired, increase the cinacalcet dose in increments of 0.2 mg/kg/d to a maximum daily dose of 2.5 mg/kg (not exceeding 180 mg) based on PTH levels provided that albumin-corrected calcium serum levels remain more than 2.2 mmol/L. Dose titration intervals should be at least 4 weeks.
12. Cinacalcet can be given orally or by nasogastric/gastric tube, once daily.
13. Use the minimal effective cinacalcet dose to maintain PTH levels in the desired PTH target range, taking into account its effects on calcium and phosphate concentrations.
14. Decrease the cinacalcet dose when PTH levels are in the lower target range between 100 and 150 pg/mL, low for the individual patient or declining too rapidly, and to discontinue cinacalcet when PTH concentrations are below the target range.
15. Maintain serum calcium levels within the normal range for age, by titrating conventional therapy including nutritional calcium intake, calcium-based phosphate binders, vitamin D analogues, and dialysate calcium, and by titrating cinacalcet dose.
16. Decrease or withdraw cinacalcet when albumin-corrected serum calcium levels fall to less than 2.2 mmol/L.
Monitoring cinacalcet therapy
17. Monitor serum calcium levels within 1 week of starting cinacalcet therapy, weekly during the titration phase, and at least monthly when maintenance dose has been established in a patient.
18. Check serum PTH levels monthly.
19. Inform children and their caregivers of hypocalcemia symptoms, the importance of medication adherence, and instructions on serum calcium monitoring. Caution about other medications which may prolong QTc interval or interact with cinacalcet.
20. Withhold cinacalcet when albumin-corrected serum calcium levels are less than 2.0 mmol/L and/or ionized calcium levels are less than 1.0 mmol/L. Cinacalcet may be restarted in a lower dose when serum calcium levels return to the higher end of the normal range.
21. Withdraw cinacalcet in case of symptomatic hypocalcemia, including paresthesia, myalgia, cramps, tetany and convulsions, long QT interval or severe side effects.
Treating a pediatric patient with persistent severe SHPT despite conventional therapy
22. The guideline authors suggest that parathyroidectomy be considered in case of severe and persistent SHPT despite optimized cinacalcet and conventional therapy, including active vitamin D.
“Given the limited available evidence, the strength of these statements are weak to moderate, and must be carefully considered by the treating physician and adapted to individual patient needs as appropriate,” the authors concluded.
The working group highlighted that use of cinacalcet in children requires further research including studies with key patient level outcomes, such as bone pain, parathyroidectomy, cardiovascular events, bone fractures, or mortality.
Reference
Bacchetta J, Schmitt CP, Ariceta G, et al. Cinacalcet use in paediatric dialysis: a position statement from the European Society for Paediatric Nephrology and the Chronic Kidney Disease-Mineral and Bone Disorders Working Group of the ERA-EDTA. Nephrol Dial Transplant 1–18. doi:10.1093/ndt/gfz159
