Sensipar

Sensipar is a positive modulator of the calcium sensing receptor indicated for:

• Secondary Hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on dialysis. (
  1.1       Secondary Hyperparathyroidism

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

  [see Clinical Studies (

  14.1

  )].

  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

  [see Warnings and Precautions (

  5.1

  )]

  .
  )
  
  
  Limitations of Use:
   Sensipar is not indicated for use in patients with CKD who are not on dialysis

• Hypercalcemia in adult patients with Parathyroid Carcinoma (PC). (
  1.2       Parathyroid Carcinoma

  Sensipar is indicated for the treatment of hypercalcemia in adult patients with Parathyroid Carcinoma

  [see Clinical Studies (

  14.2

  )]

  .
  )
  
  
• Hypercalcemia in adult patients with primary HPT for whom parathyroidectomy would be indicated on the basis of serum calcium levels, but who are unable to undergo parathyroidectomy. (
  1.3       Primary Hyperparathyroidism

  Sensipar is indicated for the treatment of hypercalcemia in adult patients with primary HPT for whom parathyroidectomy would be indicated on the basis of serum calcium levels, but who are unable to undergo parathyroidectomy

  [see Clinical Studies (

  14.3

  )]

  .
  )

• Sensipar tablets should be taken with food or shortly after a meal (
  2.1       Administration

  Sensipar should be taken with food or shortly after a meal.

  Sensipar tablets are administered orally and should always be taken whole and not chewed, crushed, or divided.
  )  
  
  
• Tablets should always be taken whole and not divided (
  2.1       Administration

  Sensipar should be taken with food or shortly after a meal.

  Sensipar tablets are administered orally and should always be taken whole and not chewed, crushed, or divided.
  )
  
  
• Secondary HPT in patients with CKD on dialysis (
  2.2       Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease on Dialysis

  The recommended starting oral dose of Sensipar is 30 mg once daily. Serum calcium and serum phosphorus should be measured within 1 week and intact parathyroid hormone (iPTH) should be measured 1 to 4 weeks after initiation or dose adjustment of Sensipar

  [see Dosage and Administration

  (

  2.3

  )]

  . Sensipar should be titrated no more frequently than every 2 to 4 weeks through sequential doses of 30, 60, 90, 120, and 180 mg once daily to target iPTH levels of 150 to 300 pg/mL. Serum iPTH levels should be assessed no earlier than 12 hours after dosing with Sensipar.

  Sensipar can be used alone or in combination with vitamin D sterols and/or phosphate binders.

  During dose titration, serum calcium levels should be monitored frequently and if levels decrease below the normal range, appropriate steps should be taken to increase serum calcium levels, such as by providing supplemental calcium, initiating or increasing the dose of calcium-based phosphate binder, initiating or increasing the dose of vitamin D sterols, or temporarily withholding treatment with Sensipar

  [see

  Dosage and Administration (

  2.4

  ) and

  Warnings and Precautions (

  5.1

  )]

  .
  ):
  
  ○ Starting dose is 30 mg once daily.
  
  ○ Titrate dose no more frequently than every 2 to 4 weeks through sequential doses of 30, 60, 90, 120, and 180 mg once daily as necessary to achieve targeted intact parathyroid hormone (iPTH) levels.
  
  ○ iPTH levels should be measured no earlier than 12 hours after most recent dose.
  
  
• Hypercalcemia in patients with PC or hypercalcemia in patients with primary HPT (
  2.3       Patients with Parathyroid Carcinoma and Primary Hyperparathyroidism

  The recommended starting oral dose of Sensipar is 30 mg twice daily.

  The dose of Sensipar should be titrated every 2 to 4 weeks through sequential doses of 30 mg twice daily, 60 mg twice daily, and 90 mg twice daily, and 90 mg 3 or 4 times daily as necessary to normalize serum calcium levels.  Serum calcium should be measured within 1 week after initiation or dose adjustment of Sensipar

  [see

  Dosage and Administration (

  2.4

  ) and

  Warnings and Precautions (

  5.1

  )].
  ):
  
  ○ Starting dose is 30 mg twice daily.
  
  ○ Titrate dose every 2 to 4 weeks through sequential doses of 30 mg twice daily, 60 mg twice daily, 90 mg twice daily, and 90 mg three or four times daily as necessary to normalize serum calcium levels.
  
  
• Once the maintenance dose has been established, monitor serum calcium approximately monthly for patients with secondary HPT and every 2 months for patients with PC or primary HPT (
  2.4       Switching from Parsabiv (etelcalcetide) to Sensipar

  Discontinue etelcalcetide for at least 4 weeks prior to starting Sensipar. Ensure corrected serum calcium is at or above the lower limit of normal prior to Sensipar initiation

  [see Warnings and Precautions (

  5.1

  )]

  . Initiate Sensipar treatment at a starting dose of 30 mg once daily.
  )

Sensipar is available as film-coated tablets. 

Sensipar tablets are formulated as light-green, film-coated, oval-shaped tablets marked with “AMG” on one side and “30” or “60” or “90” on the opposite side of the 30 mg, 60 mg, or 90 mg strengths, respectively.

• Pediatric Use: A fatal outcome was reported in a pediatric clinical trial patient with severe hypocalcemia.  Sensipar is not indicated for use in pediatric patients. (
  8.4       Pediatric Use

  The safety and efficacy of Sensipar have not been established in pediatric patients.

  The use of Sensipar for the treatment of secondary HPT in pediatric patients with CKD on dialysis was evaluated in two randomized, controlled studies (Pediatric Study 1 and Study 2) where 47 pediatric patients aged 6 years to less than 18 years received at least one dose of Sensipar and in one single-arm study (Pediatric Study 3) where 17 pediatric patients aged 28 days to less than 6 years received at least one dose of Sensipar. Dosing with Sensipar in Pediatric Study 1 was stopped because of a fatality in a Sensipar-treated individual. The individual was noted to be severely hypocalcemic at the time of death. The cause of death was multifactorial and a contribution of Sensipar to the death could not be excluded

  [see Warnings and Precautions (

  5.1

  )]

  .  Study 1 was terminated and changes to Sensipar dosing after the fatality were implemented in Pediatric Study 2 and Study 3 to minimize the risk of severe hypocalcemia. The data in Pediatric Studies 2 and 3 were insufficient to establish the safety and efficacy of Sensipar for the treatment of secondary HPT in pediatric patients with CKD on dialysis. In aggregate, the pediatric studies did not establish a safe and effective Sensipar dosing regimen for the pediatric population.
  )

The following adverse reactions are discussed in greater detail in other sections of labeling:

• Hypocalcemia
  [see Warnings and Precautions (
  5.1       Hypocalcemia

  Sensipar lowers serum calcium and can lead to hypocalcemia

  [see Adverse Reactions (

  6.1

  )].

  Significant lowering of serum calcium can cause paresthesias, myalgias, muscle spasms, tetany, seizures, QT interval prolongation and ventricular arrhythmia.  Life threatening events and fatal outcomes associated with hypocalcemia have been reported in patients treated with Sensipar, including in pediatric patients.  The safety and effectiveness of Sensipar have not been established in pediatric patients

  [see Pediatric Use (

  8.4

  )].

  Sensipar is not indicated for patients with CKD not on dialysis

  [see

  I

  ndications and Usage

  (

  1

  )]

  .  In patients with secondary HPT and CKD not on dialysis, the long-term safety and efficacy of Sensipar have not been established.  Clinical studies indicate that Sensipar-treated patients with CKD not on dialysis have an increased risk for hypocalcemia compared with Sensipar-treated patients with CKD on dialysis, which may be due to lower baseline calcium levels.  In a phase 3 study of 32 weeks duration and including 404 patients with CKD not on dialysis (302 cinacalcet, 102 placebo), in which the median dose for cinacalcet was 60 mg per day at the completion of the study, 80% of Sensipar-treated patients experienced at least one serum calcium value < 8.4 mg/dL compared with 5% of patients receiving placebo.

  QT

  Interval

  Prolongation

  and

  V

  entricular

  A

  rr

  h

  ythmia

  Decreases in serum calcium can also 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 congenital long QT syndrome, history of QT interval prolongation, family history of long QT syndrome or sudden cardiac death, and other 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.

  Seizures

  In clinical studies, seizures (primarily generalized or tonic-clonic) were observed in 1.4% (43/3049) of Sensipar-treated patients and 0.7% (5/687) of placebo-treated patients. While the basis for the reported difference in seizure rate is not clear, the threshold for seizures is lowered by significant reductions in serum calcium levels. Monitor serum calcium levels in patients with seizure disorders receiving Sensipar

  .

  Concurrent

  Administration with Other Calcium-Lowering Drug Products

  Concurrent administration of Sensipar with calcium-lowering drugs including other calcium-sensing receptor agonists could result in severe hypocalcemia.  Closely monitor serum calcium in patients receiving Sensipar and concomitant therapies known to lower serum calcium levels.

  Patient Education and Hypocalcemia Treatment

  Educate patients on the symptoms of hypocalcemia and advise them to contact a healthcare provider if they occur.  If corrected serum calcium falls below the lower limit of normal or symptoms of hypocalcemia develop, start or increase calcium supplementation (including calcium, calcium-containing phosphate binders, and/or vitamin D sterols or increases in dialysate calcium concentration).  Sensipar dose reduction or discontinuation of Sensipar may be necessary

  [see Dosage and Administration (

  2.2

  )].
  )]
  
  
  
• Upper Gastrointestinal Bleeding
  [see Warnings and Precautions (
  5.2       Upper Gastrointestinal Bleeding

  Cases of gastrointestinal bleeding, mostly upper gastrointestinal 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 when receiving Sensipar treatment. Monitor patients for worsening of common GI adverse reactions of nausea and vomiting associated with Sensipar

  [see Adverse Reactions (

  6.1

  )]

  and for signs and symptoms of GI bleeding and ulcerations during Sensipar therapy. Promptly evaluate and treat any suspected GI bleeding.
  )]
  
  
  
• Hypotension, Worsening Heart Failure and/or Arrhythmias 
  [
  see Warnings and
  Precautions
  (
  5.3        Hypotension, Worsening Heart Failure and/or Arrhythmias

  In postmarketing safety surveillance, isolated, idiosyncratic cases of hypotension, worsening heart failure, and/or arrhythmia have been reported in patients with impaired cardiac function, in which a causal relationship to Sensipar could not be completely excluded and which may be mediated by reductions in serum calcium levels

  [see Adverse Reactions

  (

  6.2

  )].
  )]
  
  
  
• Adynamic Bone Disease
  [see Warnings and Precautions (
  5.4       Adynamic Bone Disease

  Adynamic bone disease may develop if iPTH levels are suppressed below 100 pg/mL. One clinical study evaluated bone histomorphometry in patients treated with Sensipar for 1 year. Three patients with mild hyperparathyroid bone disease at the beginning of the study developed adynamic bone disease during treatment with Sensipar. Two of these patients had iPTH levels below 100 pg/mL at multiple time points during the study. In three 6-month, phase 3 studies conducted in patients with CKD on dialysis, 11% of patients treated with Sensipar had mean iPTH values below 100 pg/mL during the efficacy-assessment phase. If iPTH levels decrease below 150 pg/mL in patients treated with Sensipar, the dose of Sensipar and/or vitamin D sterols should be reduced or therapy discontinued.
  )]