Indication and Limitations of Use

Sensipar® (cinacalcet) is indicated for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on dialysis.
Sensipar® is not indicated for use in patients with CKD who are not on dialysis because of an increased risk of hypocalcemia.
KDIGO® guidelines suggest calcimimetics as one of the first-line treatment options for sHPT.10

Sensipar® plus vitamin D and phosphate binders*
lowered PTH, phosphorus, and calcium2

PHASE 3 POOLED STUDIES

PTH
chart-gallery-image-pth
Phosphorus
chart-gallery-image-phosphorus
Calcium
chart-gallery-image-calcium

Results are pooled from a retrospective analysis of three phase 3, 6-month, multicenter, randomized, double-blind, placebo-controlled clinical studies comparing Sensipar® with placebo in patients with CKD on dialysis with iPTH ≥ 300 pg/mL and serum calcium ≥ 8.4 mg/dL (N = 1,136). Patients in both treatment arms could be treated with vitamin D sterols and/or phosphate binders. Mean baseline iPTH values in the Sensipar® group and placebo group were 733 pg/mL and 683 pg/mL, respectively. The primary endpoint of the study was the proportion of patients achieving PTH level ≤ 250 pg/mL during the efficacy assessment phase (EAP).1,2

*Vitamin D and/or phosphate binders. Not all patients received vitamin D or phosphate binders.

KDIGO = Kidney Disease Improving Global Outcomes; sHPT = secondary hyperparathyroidism.

Initiating Sensipar® with vitamin D and phosphate binders* at iPTH 300–500 pg/mL helped 60% of patients achieve study PTH treatment goal1,16†

chart-initiating-sensipar-vitamin-D-and-phosphate-binders
Results are pooled from a retrospective analysis of three phase 3, 6-month, multicenter, randomized, double-blind, placebo-controlled clinical studies comparing Sensipar® with placebo in patients with CKD on dialysis with iPTH ≥ 300 pg/mL and serum calcium ≥ 8.4 mg/dL (N = 1,136). Patients in both treatment arms could be treated with vitamin D sterols and/or phosphate binders. Mean baseline iPTH values in the Sensipar® group and placebo group were 733 pg/mL and 683 pg/mL, respectively. The primary endpoint of the study was the proportion of patients achieving PTH level ≤ 250 pg/mL during the efficacy assessment phase (EAP).1,2

Initiating Sensipar® with vitamin D and phosphate binders* at iPTH 300–500 pg/mL helped 40% of patients achieve PTH ≤ 300 pg/mL and phosphorus 3.5–5.5 mg/dL17

chart-initiating-sensipar-vitamin-D-helped-40-percent
Results are pooled from a retrospective analysis of three phase 3, 6-month, multicenter, randomized, double-blind, placebo-controlled clinical studies comparing Sensipar® with placebo in patients with CKD on dialysis with iPTH ≥ 300 pg/mL and serum calcium ≥ 8.4 mg/dL (N = 1,136). Patients in both treatment arms could be treated with vitamin D sterols and/or phosphate binders. Mean baseline iPTH values in the Sensipar® group and placebo group were 733 pg/mL and 683 pg/mL, respectively. The primary endpoint of the study was the proportion of patients achieving PTH level ≤ 250 pg/mL during the efficacy assessment phase (EAP).1,2

PHASE 4 STUDIES

Sensipar® plus vitamin D and phosphate binders*: an integrated approach to secondary HPT treatment in patients on dialysis11-13

For prevalent patients on dialysis

Sensipar® plus vitamin D and phosphate binders* lowered PTH, phosphorus, and calcium11

OPTIMA was a multicenter open-label study conducted in patients on dialysis with uncontrolled secondary HPT (N = 552). Subjects were randomized 2:1 to receive Sensipar® with or without vitamin D and phosphate binders or vitamin D and phosphate binders. Key inclusion criteria were mean baseline iPTH ≥ 300 pg/mL and < 800 pg/mL, and mean baseline corrected serum calcium ≥ 8.4 mg/dL. The unrestricted use of vitamin D and phosphate binders, if prescribed, was permitted complete treatment flexibility, with no medication or dosage restrictions. In the Sensipar® group, patients were to be treated according to the predefined treatment algorithm. The primary endpoint was the proportion of patients achieving a mean iPTH ≤ 300 pg/mL during the 7-week efficacy assessment phase (EAP).11
For incident patients on dialysis

Sensipar® plus vitamin D and phosphate binders* lowered PTH phosphorus and calcium12

The Incident Dialysis Study was a randomized open-label study of patients with CKD on dialysis 3–12 months with iPTH 300–800 pg/mL who were randomized to receive Sensipar® with or without vitamin D and phosphate binders or vitamin D and phosphate binders, if prescribed, per physician discretion (N = 309). The primary endpoint was achievement of a ≥ 30% PTH reduction from baseline at 6 months. A 4-week prerandomization washout of vitamin D and Sensipar®, if required, was followed by a 22-week dose-titration phase, 4-week efficacy assessment phase (EAP) at month 6, a 22-week maintenance phase, and a second EAP at month 12. After the second EAP, both Sensipar® and active vitamin D treatment were withheld for a 4-week end-of-study washout phase.12

CALCIUM MANAGEMENT

Managing calcium in patients taking Sensipar® (cinacalcet)1

step-initiate-sensipar Sensipar® treatment should not be initiated if serum calcium is less than the lower limit of the normal range (8.4 mg/dL).
Serum calcium should be measured within 1 week after initiation or dose adjustment of Sensipar®. Once the maintenance dose has been established, serum calcium should be measured approximately monthly.
step-adjust-monitor If serum calcium falls below 8.4 mg/dL but remains above 7.5 mg/dL, or if symptoms of hypocalcemia occur, calcium-containing phosphate binders and/or vitamin D sterols can be used to raise serum calcium.
step-withhold-monitor If serum calcium falls below 7.5 mg/dL, or if symptoms of hypocalcemia persist and the vitamin D dose cannot be increased, withhold administration of Sensipar® until serum calcium reaches 8.0 mg/dL and/or symptoms of hypocalcemia have resolved.
Treatment should be reinitiated using the next lowest dose of Sensipar®.

CALCIUM LEVELS

Serum calcium reductions with Sensipar® were lower among patients initiated at the lowest baseline calcium levels (8.4–9.5 mg/dL)14*

Retrospective analysis of pooled phase 3 data including patients with iPTH ≥ 300 pg/mL and calcium ≥ 8.4 mg/dL who were treated with Sensipar® (N = 656) to further characterize reductions in serum calcium. Patients were stratified according to baseline calcium (8.4–9.5 pg/mL, > 9.5–10.2 pg/mL, and > 10.2 pg/mL). Mean calcium levels during the efficacy assessment phase (2 studies, weeks 13–26; 1 study, weeks 17–26) were compared with baseline levels.14

*Sensipar®-treated patients only.

After initiation of Sensipar®, patients who maintained calcium ≥ 8.4 mg/dL had the lowest baseline serum PTH levels15

Results are from an observational study that included all new Sensipar® users with calcium ≥ 8.4 mg/dL at Sensipar® initiation who received in-center hemodialysis at a large dialysis organization (LDO) from January 1, 2011 to December 31, 2013, and were enrolled in the LDO’s prescription benefits service (N = 13,723). Patients were categorized as those who did not experience a reduction in calcium to < 8.4 mg/dL and those in whom calcium fell to levels 8.0–8.3 mg/dL, 7.5–7.9 mg/dL, and < 7.5 mg/dL. Baseline patient characteristics were compared between these levels.15

Reductions in calcium with Sensipar® were most prominent in the first week of therapy but stabilized over time12

Randomized open-label study of patients with CKD on dialysis 3–12 months with iPTH 300–800 pg/mL who were randomized to receive Sensipar® with or without vitamin D and phosphate binders or vitamin D and phosphate binders, if prescribed, per physician discretion (N = 309). The primary endpoint was proportion of patients achieving a ≥ 30% PTH reduction from baseline at 6 months. Total treatment duration was 12 months.12
Important Safety Information

Contraindication: Sensipar® (cinacalcet) treatment initiation is contraindicated if serum calcium is less than the lower limit of the normal range (8.4 mg/dL).

Hypocalcemia: Sensipar® lowers serum calcium and can lead to hypocalcemia. Life threatening events and fatal outcomes associated with hypocalcemia have been reported in patients treated with Sensipar®, including pediatric patients. The safety and effectiveness of Sensipar® have not been established in pediatric patients.

Decreases in serum calcium can prolong the QT interval, potentially resulting in ventricular arrhythmia. Cases of QT prolongation and ventricular arrhythmia have been reported in patients treated with Sensipar®. Patients with conditions that predispose to QT interval prolongation and ventricular arrhythmia may be at increased risk for QT interval prolongation and ventricular arrhythmias if they develop hypocalcemia due to Sensipar®. Closely monitor corrected serum calcium and QT interval in patients at risk receiving Sensipar®.

Significant reductions in calcium may lower the threshold for seizures. Monitor serum calcium levels in patients with seizure disorders on Sensipar®.

Concurrent administration of Sensipar® with calcium-lowering drugs including other calcimimetics could result in severe hypocalcemia. Parsabiv™ (etelcalcetide) and Sensipar® should not be given together. Closely monitor serum calcium in patients receiving Sensipar® and concomitant therapies known to lower serum calcium levels.

Serum calcium and serum phosphorus should be measured within 1 week and PTH should be measured 1 to 4 weeks after initiation or dose adjustment of Sensipar®. Once the maintenance dose has been established, serum calcium and serum phosphorus should be measured approximately monthly, and PTH every 1 to 3 months.

Upper Gastrointestinal Bleeding: Cases of gastrointestinal (GI) bleeding, mostly upper GI bleeding, have occurred in patients using calcimimetics, including Sensipar®, from postmarketing and clinical trial sources. The exact cause of GI bleeding in these patients is unknown.

Patients with risk factors for upper GI bleeding, such as known gastritis, esophagitis, ulcers or severe vomiting, may be at increased risk for GI bleeding with Sensipar®. Monitor patients for worsening of common Sensipar® GI adverse reactions and for signs and symptoms of GI bleeding and ulcerations during Sensipar® therapy.

Hypotension, Worsening Heart Failure and/or Arrhythmias: In Sensipar® postmarketing use, isolated, idiosyncratic cases of hypotension, worsening heart failure, and/or arrhythmia were reported in patients with impaired cardiac function. The causal relationship to Sensipar® therapy could not be completely excluded and may be mediated by reductions in serum calcium levels.

Adynamic Bone: Adynamic bone disease may develop if intact parathyroid hormone (iPTH) levels are suppressed below 100 pg/mL.

Adverse Reactions: In clinical trials of patients with secondary HPT comparing Sensipar® to placebo, the most commonly reported side effects were nausea (31% vs. 19%), vomiting (27% vs. 15%), and diarrhea (21% vs. 20%).

Indication

Sensipar® (cinacalcet) is indicated for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on dialysis.

Limitations of Use:

Sensipar® is not indicated for use in patients with CKD who are not on dialysis because of an increased risk of hypocalcemia.

References: 1. Sensipar® (cinacalcet) prescribing information, Amgen. 2. Data on file, Amgen; [Cinacalcet Integrated Analyses of Efficacy; 2003]. 3. Goodman WG. Calcium and phosphorus metabolism in patients who have chronic kidney disease. Med Clin North Am. 2005;89:631-647. 4. Hruska KA, Mathew S, Lund R, Qiu P, Pratt R. Hyperphosphatemia of chronic kidney disease. Kidney Int. 2008;74:148-157. 5. Wesseling-Perry K, Harkins GC, Wang HJ, et al. The calcemic response to continuous parathyroid hormone (PTH)(1-34) infusion in end-stage kidney disease varies according to bone turnover: a potential role for PTH(7-84). J Clin Endocrinol Metab. 2010;95:2772-2780. 6. Komaba H, Shiizaki K, Fukagawa M. Pharmacotherapy and interventional treatments for secondary hyperparathyroidism: current therapy and future challenges. Expert Opin Biol Ther. 2010;10:1729-1742. 7. Goodman WG, Quarles LD. Vitamin D, calcimimetics, and phosphate-binders. In: Brenner BM, Levine SA, eds. Brenner & Rector’s The Kidney. 8th ed. Philadelphia, PA: Saunders Elsevier; 2008:1904-1927. 8. Teng M, Wolf M, Lowrie E, Ofsthun N, Lazarus JM, Thadhani R. Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med. 2003;349:446-456. 9. Data on file, Amgen; [ESRD Dialysis Patient Chart Audit; Q2 2014]. 10. Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl. 2017;7:1–59. 11. Messa P, Macário F, Yaqoob M, et al. The OPTIMA study: assessing a new cinacalcet (Sensipar/Mimpara) treatment algorithm for secondary hyperparathyroidism. Clin J Am Soc Nephrol. 2008;3:36-45. 12. Ureña-Torres P, Bridges I, Christiano C, et al. Efficacy of cinacalcet with low-dose vitamin D in incident haemodialysis subjects with secondary hyperparathyroidism. Nephrol Dial Transplant. 2013;28:1241-1254. 13. Data on file, Amgen; [Clinical Study Report 20070360–Incident Dialysis Study; June 27, 2012]. 14. Data on file, Amgen; [Pooled Phase 3 PTH and Calcium Reductions by Baseline Calcium Analysis; November 2012]. 15. Brunelli SM, Dluzniewski P, Cooper K, Do T, Sibbel S, Bradbury BD. Serum calcium reductions among patients on hemodialysis initiating cinacalcet. Poster presented at: The American Society of Nephrology Renal Week; November 11-16, 2014; Philadelphia, PA. 16. Food and Drug Administration Center for Drug Evaluation and Research. Clinical review for NDA 21-688. Available at: http://www.accessdata.fda.gov/ drugsatfda_docs/nda/2004/21-688_Sensipar.cfm. Accessed June 21, 2015. 17. Data on file, Amgen; [Pooled Phase 3 Concurrent Achievement of PTH and Serum Phosphorus Targets During the Efficacy Assessment Phase; November 2014]. 18. Data on file, Amgen; [Cinacalcet New to Brand Patient Persistency; 2008-2014]. 19. Centers for Medicare & Medicaid Services (CMS). Implementation of the transitional drug add-on payment adjustment. Transmittal R1889OTN. https://www.cms.gov/Regulations-and-Guidance/ Guidance/ Transmittals/2017Downloads/R1889OTN.pdf. Accessed August 17, 2017.