Treatment of secondary hyperparathyroidism: the clinical utility of etelcalcetide

Figures & data

Figure 1 Regulation of PTH synthesis and secretion by CaSR and VDR in parathyroid glands.

Abbreviations: Ca⁺⁺, ionized calcium; CaSR, calcium-sensing receptor; PTH, parathyroid hormone; VDR, vitamin D receptor.

Table 1 Treatment options for secondary hyperparathyroidism

Treatment	Dose formulation	Initial dose	Most common AEs
Phosphate binders
Calcium-containing
Calcium acetate (prescription for ESRD)	667 mg capsules	667–1,334 mg	Nausea, vomiting, hypercalcemia
Calcium carbonate (OTC)	250 to 1,000 mg tablets	500–1,000 mg	Nausea, vomiting, diarrhea, dyspepsia, abdominal pain, flatulence, constipation
Non-calcium-containing
Sevelamer hydrochloride/carbonate	800 mg tablets, 2.4 g packets powder for oral suspension	800–1,600 mg TID with meals	Headache, diarrhea, stomach upset
Lanthanum carbonate (for ESRD)	250, 500, 750, and 1,000 mg chewable tablets	1,500 mg daily	Diarrhea, nausea, abdominal pain, vomiting
Vitamin D analogs
Calcitriol	Oral (0.25 µg capsules)	0.25 µg daily	Hypercalcemia, headache, abdominal pain, nausea, rash, urinary tract infection
	Injectable (1 µg/mL)	1–2 µg three times weekly or every other day	Weakness, headache, somnolence, nausea, vomiting, dry mouth, constipation, muscle pain, bone pain, metallic taste, anorexia, abdominal pain, epigastric discomfort
Doxercalciferol	Oral (0.5, 1.0, and 2.5 µg capsules)	1 µg daily (predialysis) 10 µg three times weekly at dialysis	Edema, headache, malaise, dyspepsia, nausea, vomiting, dizziness, dyspnea (similar for both dosing forms)
	Injectable 4 µg/2 mL	4 µg three times weekly at the end of dialysis or every other day
Paricalcitol	Oral (1, 2, and 4 µg capsules), injectable	1–2 µg daily (PTH ≤500 pg/mL) or 2–4 µg every other day (PTH >500 pg/mL)	Diarrhea, hypertension, dizziness, vomiting
Calcimimetic
Cinacalcet	30, 60, and 90 mg tablets	30 mg once daily	Nausea, vomiting, diarrhea

Notes: Calcium carbonate, Medline Plus Drug Information, Available from: www.nlm.nih.gov/medlineplus/druginfo/meds/a601032.html. Data from the following references.^16,57–63

Abbreviations: AE, adverse event; ESRD, end-stage renal disease; OTC, over the counter; PTH, parathyroid hormone; TID, three times per day.

Table 2 Stages of chronic kidney disease

Stage	Definition	GFR (mL/min/1.73 m^2)
1	Kidney damage and normal or elevated GFR	≥90
2	Kidney damage and mild reduction in GFR	60–89
3	Moderate reduction in GFR	30–59
4	Severe reduction in GFR	15–29
5	Kidney failure	<15 (or dialysis)

Note: Data from Block et al.³⁰

Abbreviation: GFR, glomerular filtration rate.

Table 3 Incidence (%) of most frequent adverse drug reactions

Most frequent adverse events	Placebo-controlled studies		Cinacalcet-controlled studies
	Placebo n=513	Etelcalcetide n=503	Cinacalcet n=341	Etelcalcetide n=338
Diarrhea	8.6	10.7	10.3	6.2
Nausea	6.2	10.7	22.6	18.3
Vomiting	5.1	8.9	13.8	13.3
Calcium reduction	10.1	63.8	59.8	68.9
Hypocalcemiaa	0.2	7.0	2.3	5.0
Hyperkalemia	3.1	4.4	5.3	3.8
Muscle spasms	6.6	11.5	5.9	6.5
Paraesthesia	1.2	6.2	2.6	3.3
Hypotension	–	–	2.9	6.8

Note:

a Hypocalcemia definition: symptomatic reduction in serum corrected calcium <8.3 mg/dL.

MoeSMThadhaniRWhat have we learned about chronic kidney disease-mineral bone disorder from the EVOLVE and PRIMO trials?Curr Opin Nephrol Hypertens20132265165524100218

 PubMed Web of Science ®Google Scholar

KovesdyCPKalantar-ZadehKVitamin D receptor activation and survival in chronic kidney diseaseKidney Int200873121355136318288097

 PubMed Web of Science ®Google Scholar

ThadhaniRAppelbaumEPritchettYVitamin D therapy and cardiac structure and function in patients with chronic kidney disease: the PRIMO randomized controlled trialJAMA2012307767468422337679

 PubMed Web of Science ®Google Scholar

BlockGAMartinKJde FranciscoALCinacalcet for secondary hyperparathyroidism in patients receiving hemodialysisN Engl J Med20043501516152515071126

 PubMed Web of Science ®Google Scholar