SENSIPAR- cinacalcet hydrochloride tablet, coated

United States - English - NLM (National Library of Medicine)

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Active ingredient:
CINACALCET HYDROCHLORIDE (UNII: 1K860WSG25) (CINACALCET - UNII:UAZ6V7728S)
Available from:
A-S Medication Solutions
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
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 )] . Sensipar is indicated for the treatment of hypercalcemia in adult patients with Parathyroid Carcinoma [see Clinical Studies ( 14.2 )] . 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 treatment initiation is contraindicated if serum calcium is less than the lower limit of the normal range [see Warnings and Precautions ( 5.1 )]. Risk Summary Limited case reports of Sensipar use in pregnant women are insufficient to inform a drug associated
Product summary:
Product: 50090-4470 NDC: 50090-4470-0 30 TABLET, COATED in a BOTTLE, PLASTIC
Authorization status:
New Drug Application
Authorization number:
50090-4470-0

SENSIPAR- cinacalcet hydrochloride tablet, coated

A-S Medication Solutions

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use SENSIPAR safely and effectively. See full

prescribing information for SENSIPAR.

SENSIPAR (cinacalcet) tablets, for oral use

Initial U.S. Approval: 2004

INDICATIONS AND USAGE

Sensipar is a calcium-sensing receptor agonist indicated for:

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

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)

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)

DOSAGE AND ADMINISTRATION

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

Tablets should always be taken whole and not divided (2.1)

Secondary HPT in patients with CKD on dialysis (2.2):

○ 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):

○ 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)

DOSAGE FORMS AND STRENGTHS

Tablets: 30, 60, and 90 mg tablets (3)

CONTRAINDICATIONS

Sensipar treatment initiation is contraindicated if serum calcium is less than the lower limit of the normal range. (4, 5.1)

WARNINGS AND PRECAUTIONS

Hypocalcemia: Life threatening events and fatal outcomes were reported. Hypocalcemia can prolong QT interval, lower

the threshold for seizures, and cause hypotension, worsening heart failure, and/or arrhythmia. Monitor serum calcium

carefully for the occurrence of hypocalcemia during treatment. (2.4, 5.1)

Upper Gastrointestinal (GI) Bleeding: Patients with risk factors for upper GI bleeding may be at increased risk. Monitor

patients and promptly evaluate and treat any suspected GI bleeding. (5.2)

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. (5.3)

Adynamic Bone Disease: May develop if iPTH levels are suppressed below 100 pg/mL. (5.4)

ADVERSE REACTIONS

The most common adverse reactions (i.e., ≥ 25%) associated with Sensipar were nausea and vomiting. (6)

To report SUSPECTED ADVERSE REACTIONS, contact Amgen Medical Information at 1-800-77-AMGEN (1-

800-772-6436) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

Co-administration with a strong CYP3A4 inhibitor may increase serum levels of cinacalcet. Dose adjustment and

monitoring of iPTH serum phosphorus and serum calcium may be required. (7.1)

Cinacalcet is a strong inhibitor of CYP2D6. Dose adjustments may be required for concomitant medications that are

predominantly metabolized by CYP2D6. (7.2)

USE IN SPECIFIC POPULATIONS

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)

__________________________________________________________________________________________________________________________________

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 8/2019

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

1.1 Secondary Hyperparathyroidism

®

1.2 Parathyroid Carcinoma

1.3 Primary Hyperparathyroidism

2 DOSAGE AND ADMINISTRATION

2.1 Administration

2.2 Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease on Dialysis

2.3 Patients with Parathyroid Carcinoma and Primary Hyperparathyroidism

2.4 Switching from Parsabiv (etelcalcetide) to Sensipar

2.5 Monitoring for Hypocalcemia

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Hypocalcemia

5.2 Upper Gastrointestinal Bleeding

5.3 Hypotension, Worsening Heart Failure and/or Arrhythmias

5.4 Adynamic Bone Disease

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Strong CYP3A4 Inhibitors

7.2 CYP2D6 Substrates

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Renal Impairment

8.7 Hepatic Impairment

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

14.1 Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease on Dialysis

14.2 Parathyroid Carcinoma

14.3 Patients with Hypercalcemia Due to Primary Hyperparathyroidism

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

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)].

1.2 Parathyroid Carcinoma

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

[see Clinical Studies (14.2)].

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)].

Sections or subsections omitted from the full prescribing information are not listed.

2 DOSAGE AND ADMINISTRATION

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.

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)].

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)].

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.

2.5 Monitoring for Hypocalcemia

Once the maintenance dose has been established, serum calcium should be measured approximately

monthly for patients with secondary hyperparathyroidism with CKD on dialysis, and every 2 months for

patients with parathyroid carcinoma or primary hyperparathyroidism [see Dosage and Administration

(2.2, 2.3)].

For secondary hyperparathyroidism patients with CKD on dialysis, 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. If serum calcium falls

below 7.5 mg/dL, or if symptoms of hypocalcemia persist and the dose of vitamin D cannot be

increased, withhold administration of Sensipar until serum calcium levels reach 8.0 mg/dL and/or

symptoms of hypocalcemia have resolved. Treatment should be reinitiated using the next lowest dose of

Sensipar [see Dosage and Administration (2.2)].

3 DOSAGE FORMS AND STRENGTHS

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.

4 CONTRAINDICATIONS

Sensipar treatment initiation is contraindicated if serum calcium is less than the lower limit of the normal

range [see Warnings and Precautions (5.1)].

5 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 Indications 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 Ventricular Arrhythmia

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)].

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.

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)].

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.

6 ADVERSE REACTIONS

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

Hypocalcemia [see Warnings and Precautions (5.1)]

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

Hypotension, Worsening Heart Failure and/or Arrhythmias [see Warnings and Precautions (5.3)]

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

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed

in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another

drug and may not reflect the rates observed in clinical practice.

Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease on Dialysis

In three double-blind, placebo-controlled clinical trials, 1126 patients with CKD on dialysis received

study drug (656 Sensipar, 470 placebo) for up to 6 months. The most frequently reported adverse

reactions are listed in Table 1.

Seizures were observed in 1.4% (13/910) of Sensipar-treated patients and 0.7% (5/641) of placebo-

treated patients across all completed placebo-controlled trials.

Table 1. Adverse Reactions with Frequency ≥ 5% in Patients on Dialysis in

Short-Term Studies for up to 6 Months

Placebo

Sens ipar

(n = 470)

(n = 656)

Event*:

Nausea

Vomiting

Diarrhea

Myalgia

Dizziness

Hypertension

Asthenia

Anorexia

Pain Chest, Non-Cardiac

Dialysis Access Site Infection

*Included are events that were reported at a greater incidence in the Sensipar group than in the placebo

group.

In a randomized, double-blind placebo-controlled study of 3883 patients with secondary HPT and CKD

receiving dialysis in which patients were treated for up to 64 months (mean duration of treatment was

21 months in the Sensipar group), the most frequently reported adverse reactions (incidence of ≥ 5% in

the Sensipar group and a difference ≥ 1% compared to placebo) are listed in Table 2.

Table 2. Frequency of Adverse Reactions in Dialysis Patients Treated for up to

64 Months in a Long-Term Study

Placebo (n = 1923)

Sensipar (n = 1938)

3699 subject-years

4044 subject-years

Percent of subjects reporting

Adverse Reactions (%)

90.9

93.2

Nausea

15.5

29.1

Vomiting

13.7

25.6

Diarrhea

18.7

20.5

Dyspnea

11.5

13.4

Cough

11.7

Hypotension

10.5

11.6

Headache

11.5

Hypocalcemia

11.2

Muscle spasms

11.1

Abdominal pain

10.9

1

Abdominal pain upper

Hyperkalemia

Upper respiratory tract

infection

Dyspepsia

Dizziness

Decreased appetite

Asthenia

Constipation

Adverse reactions that occurred in ≥ 5% frequency in the Sensipar group and a difference ≥ 1%

compared to the placebo group (Safety Analysis Set).

Crude incidence rate = 100 * Total number of subjects with event/ n

n = Number of subjects receiving at least one dose of study drug.

Additional adverse reaction rates from the long-term, randomized, double-blind placebo-controlled

study for Sensipar versus placebo are as follows: seizure (2.5%, 1.6%), rash (2.2%, 1.9%),

hypersensitivity reactions (9.4%, 8.3%).

Patients with Parathyroid Carcinoma and Primary Hyperparathyroidism

The safety profile of Sensipar in these patient populations is generally consistent with that seen in

patients with CKD on dialysis. Forty six patients were treated with Sensipar in a single-arm study, 29

with Parathyroid Carcinoma and 17 with intractable pHPT. Nine (20%) of the patients withdrew from the

study due to adverse events. The most frequent adverse reactions and the most frequent cause of

withdrawal in these patient populations were nausea and vomiting. Severe or prolonged cases of nausea

and vomiting can lead to dehydration and worsening hypercalcemia so careful monitoring of

electrolytes is recommended in patients with these symptoms.

Eight patients died during treatment with Sensipar in this study, 7 with Parathyroid Carcinoma (24%) and

1 (6%) with intractable pHPT. Causes of death were cardiovascular (5 patients), multi-organ failure (1

patient), gastrointestinal hemorrhage (1 patient) and metastatic carcinoma (1 patient). Adverse events of

hypocalcemia were reported in three patients (7%).

Seizures were observed in 0.7% (1/140) of cinacalcet-treated patients and 0.0% (0/46) of placebo-

treated patients in all clinical studies.

Table 3. Adverse Reactions with Frequency ≥ 10% in a Single-Arm, Open-Label

Study in Patients with Primary Hyperparathyroidism or Parathyroid Carcinoma

Sens ipar

Parathyroid

Carcinoma

(n = 29)

Intractable

pHPT

(n = 17)

Total

(n = 46)

n (%)

n (%)

n (%)

Number of Subjects Reporting

Adverse Reactions

28 (97)

17 (100)

45 (98)

Nausea

19 (66)

10 (59)

29 (63)

Vomiting

15 (52)

6 (35)

21 (46)

Paresthesia

4 (14)

5 (29)

9 (20)

Fatigue

6 (21)

2 (12)

8 (17)

Fracture

6 (21)

2 (12)

8 (17)

Hypercalcemia

6 (21)

2 (12)

8 (17)

Anorexia

6 (21)

1 (6)

7 (15)

Asthenia

5 (17)

2 (12)

7 (15)

Dehydration

7 (24)

0 (0)

7 (15)

Anemia

5 (17)

1 (6)

6 (13)

Arthralgia

5 (17)

1 (6)

6 (13)

Constipation

3 (10)

3 (18)

6 (13)

Depression

3 (10)

3 (18)

6 (13)

Headache

6 (21)

0 (0)

6 (13)

Infection Upper Respiratory

3 (10)

2 (12)

5 (11)

Pain Limb

3 (10)

2 (12)

5 (11)

n = Number of subjects receiving at least one dose of study drug.

pHPT = primary hyperparathyroidism.

In a randomized double-blind, placebo-controlled study of 67 patients with primary hyperparathyroidism

for whom parathyroidectomy would be indicated on the basis of serum calcium levels, but who are

unable to undergo surgery, the most common adverse reactions are listed in Table 4.

Table 4. Adverse Reactions Occurring in ≥ 10% of Subjects in a Double-Blind,

Placebo-Controlled Study in Patients with Primary Hyperparathyroidism

Adverse Reaction

Placebo

(n = 34)

n (%)

Cinacalcet

(n = 33)

n (%)

Nausea

6 (18)

10 (30)

Muscle spasms

0 (0)

6 (18)

Headache

2 (6)

4 (12)

Back pain

2 (6)

4 (12)

n = Number of subjects receiving at least one dose of study drug Coded using MedDRA version 16.0.

Hypocalcemia

In 26-week studies of patients with secondary HPT and CKD on dialysis 66% of patients receiving

Sensipar compared with 25% of patients receiving placebo developed at least one serum calcium value

less than 8.4 mg/dL, whereas, 29% of patients receiving Sensipar compared with 11% of patients

receiving placebo developed at least one serum calcium value less than 7.5 mg/dL. Less than 1% of

patients in each group permanently discontinued study drug due to hypocalcemia.

In a randomized, double-blind, placebo-controlled study in patients with secondary HPT and CKD

receiving dialysis in which patients were treated for up to 64 months (mean duration of treatment was 21

months in the cinacalcet group), 75% of patients receiving Sensipar compared with 29% of patients

receiving placebo developed at least one serum calcium value less than 8.4 mg/dL and 33% of

cinacalcet patients compared with 12% of patients receiving placebo had at least one serum calcium

value less than 7.5 mg/dL. Most of the cases of severe hypocalcemia less than 7.5 mg/dL (21/33 = 64%)

occurred during the first 6 months. In this trial, 1.1% of patients receiving Sensipar and 0.1% of patients

receiving placebo permanently discontinued study drug due to hypocalcemia.

During a placebo-controlled part of a 52-week study in patients with primary HPT who met criteria for

parathyroidectomy on the basis of corrected total serum calcium (> 11.3 mg/dL [2.82 mmol/L] and

≤ 12.5 mg/dL [3.12 mmol/L]), serum calcium less than 8.4 mg/dL was observed in 6.1% (2/33) of

Sensipar-treated patients and 0% (0/34) of placebo-treated patients.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post approval use of Sensipar. Because

these reactions are reported voluntarily from a population of uncertain size, it is not always possible to

reliably estimate their frequency or establish a causal relationship to drug exposure.

Rash and hypersensitivity reactions (including angioedema and urticaria), and myalgia

Isolated, idiosyncratic cases of hypotension, worsening heart failure, and/or arrhythmia have

been reported in patients with impaired cardiac function

Gastrointestinal bleeding

7 DRUG INTERACTIONS

7.1 Strong CYP3A4 Inhibitors

Cinacalcet is partially metabolized by CYP3A4. Dose adjustment of Sensipar may be required if a

patient initiates or discontinues therapy with a strong CYP3A4 inhibitor (e.g., ketoconazole,

itraconazole). The iPTH and serum calcium concentrations should be closely monitored in these

patients [see Clinical Pharmacology (12.3)].

7.2 CYP2D6 Substrates

Cinacalcet is a strong inhibitor of CYP2D6. Dose adjustments may be required for concomitant

medications that are predominantly metabolized by CYP2D6 (e.g., desipramine, metoprolol, and

carvedilol) and particularly those with a narrow therapeutic index (e.g., flecainide and most tricyclic

antidepressants) [see Clinical Pharmacology (12.3)].

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Limited case reports of Sensipar use in pregnant women are insufficient to inform a drug associated risk

of adverse developmental outcomes. In animal reproduction studies, when female rats were exposed to

cinacalcet during the period of organogenesis through to weaning at 2-3 times the systemic drug levels

(based on AUC) at the maximum recommended human dose (MRHD) of 180 mg/day, peripartum and

early postnatal pup loss and reduced pup body weight gain were observed in the presence of maternal

hypocalcemia [see Data].

The estimated background risk of major birth defects and miscarriage for the indicated populations is

unknown. In the U.S. general population, the estimated background risk of major birth defects and

miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data

Animal Data

In pregnant female rats given oral gavage doses of 2, 25, 50 mg/kg/day cinacalcet during gestation, no

teratogenicity was observed at doses up to 50 mg/kg/day (exposure 4 times those resulting with a human

oral dose of 180 mg/day based on AUC comparison). Decreased fetal body weights were observed at

all doses (less than 1 to 4 times a human oral dose of 180 mg/day based on AUC comparison) in

conjunction with maternal toxicity (decreased food consumption and body weight gain).

In pregnant female rabbits given oral gavage doses of 2, 12, 25 mg/kg/day cinacalcet during gestation,

no adverse fetal effects were observed (exposures less than with a human oral dose of 180 mg/day

based on AUC comparisons). Reductions in maternal food consumption and body weight gain were seen

at doses of 12 and 25 mg/kg/day. Cinacalcet has been shown to cross the placental barrier in rabbits.

In pregnant rats given oral gavage doses of 5, 15, 25 mg/kg/day cinacalcet during gestation through

lactation, no adverse fetal or pup (post-weaning) effects were observed at 5 mg/kg/day (exposures less

than with a human therapeutic dose of 180 mg/day based on AUC comparisons). Higher doses of 15 and

25 mg/kg/day cinacalcet (exposures 2 to 3 times a human oral dose of 180 mg/day based on AUC

comparisons) were accompanied by maternal signs of hypocalcemia (periparturient mortality and early

postnatal pup loss), and reductions in postnatal maternal and pup body weight gain.

8.2 Lactation

Risk Summary

There are no data regarding the presence of Sensipar in human milk or effects on the breastfed infant or

on milk production. Studies in rats showed that cinacalcet was excreted in the milk. The developmental

and health benefits of breastfeeding should be considered along with the mother’s clinical need for

Sensipar and any potential adverse effects on the breastfed infant from Sensipar or from the underlying

maternal condition.

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.

8.5 Geriatric Use

Of the total number of subjects (n = 1136) in clinical studies of Sensipar, 26 percent were 65 and over,

and 9 percent were 75 and over. No overall differences in the safety or effectiveness were observed

between these subjects and younger subjects, and other reported clinical experience has not identified

differences in responses between the elderly and younger subjects, but greater sensitivity of some

older individuals cannot be ruled out [see Clinical Studies (14) and Clinical Pharmacology (12.3)].

8.6 Renal Impairment

No dosage adjustment is necessary for renal impairment [see Clinical Pharmacology (12.3)].

8.7 Hepatic Impairment

Patients with moderate and severe hepatic impairment should have serum calcium, serum phosphorus,

and iPTH levels monitored closely throughout treatment with Sensipar because cinacalcet exposure

(AUC -

) is increased by 2.4 and 4.2 fold, respectively, in these patients [see Clinical

Pharmacology (12.3)].

10 OVERDOSAGE

Overdosage of Sensipar may lead to hypocalcemia. In the event of overdosage, patients should be

monitored for signs and symptoms of hypocalcemia and appropriate measures taken to correct serum

calcium levels [see Warnings and Precautions (5.1)].

Since Sensipar is highly protein bound, hemodialysis is not an effective treatment for overdosage of

Sensipar.

11 DESCRIPTION

Sensipar (cinacalcet) is a calcimimetic agent that increases the sensitivity of the calcium-sensing

receptor to activation by extracellular calcium. Sensipar tablets contain the hydrochloride salt of

cinacalcet. Its empirical formula is C

H F NHCl with a molecular weight of 393.9 g/mol

(hydrochloride salt) and 357.4 g/mol (free base). It has one chiral center having an R-absolute

configuration. The R-enantiomer is the more potent enantiomer and has been shown to be responsible

for pharmacodynamic activity.

The hydrochloride salt of cinacalcet is a white to off-white, crystalline solid that is soluble in methanol

or 95% ethanol and slightly soluble in water.

Sensipar tablets are formulated as light-green, film-coated, oval-shaped tablets for oral administration in

strengths of 30 mg, 60 mg, and 90 mg of cinacalcet as the free base equivalent (33 mg, 66 mg, and

99 mg as the hydrochloride salt, respectively).

The hydrochloride salt of cinacalcet is described chemically as N-[1-(R)-(-)-(1-naphthyl)ethyl]-3-[3-

(trifluoromethyl)phenyl]-1-aminopropane hydrochloride and has the following structural formula:

Inactive Ingredients

The following are the inactive ingredients in Sensipar tablets: pre-gelatinized starch, microcrystalline

cellulose, povidone, crospovidone, colloidal silicon dioxide and magnesium stearate. Tablets are

coated with color (Opadry

II green), clear film coat (Opadry

clear), and carnauba wax.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The calcium-sensing receptor on the surface of the chief cell of the parathyroid gland is the principal

regulator of PTH synthesis and secretion. Cinacalcet, the active ingredient in Sensipar, directly lowers

PTH levels by increasing the sensitivity of the calcium-sensing receptor to extracellular calcium. The

reduction in PTH is associated with a concomitant decrease in serum calcium levels.

12.2 Pharmacodynamics

Reduction in iPTH levels correlated with the plasma cinacalcet concentrations in patients with CKD.

The nadir in iPTH level occurs approximately 2 to 6 hours post dose, corresponding with the maximum

plasma concentration (C

) of cinacalcet. After steady-state cinacalcet concentrations are reached

(which occurs within 7 days of dose change), serum calcium concentrations remain constant over the

dosing interval in patients with CKD.

Reductions in PTH are associated with a decrease in bone turnover and bone fibrosis in patients with

CKD on dialysis and uncontrolled secondary HPT.

12.3 Pharmacokinetics

Absorption and Distribution

After oral administration of cinacalcet, C

is achieved in approximately 2 to 6 hours. Cinacalcet C

and AUC -

were increased by 82% and 68%, respectively, following administration with a high-

fat meal compared with fasting in healthy volunteers. The C

and AUC -

of cinacalcet were

increased by 65% and 50%, respectively, when cinacalcet was administered with a low-fat meal

compared with fasting.

After absorption, cinacalcet concentrations decline in a biphasic fashion with an initial half-life of

0 infinite

(0 infinite )

(0 infinite )

approximately 6 hours and terminal half-life of 30 to 40 hours. Steady-state drug levels are achieved

within 7 days, and the mean accumulation ratio is approximately 2 with once daily oral administration.

The median accumulation ratio is approximately 2 to 5 with twice daily oral administration. The AUC

and C

of cinacalcet increase proportionally over the dose range of 30 to 180 mg once daily. The

pharmacokinetic profile of cinacalcet does not change over time with once daily dosing of 30 to

180 mg. The volume of distribution is approximately 1000 L, indicating extensive distribution.

Cinacalcet is approximately 93% to 97% bound to plasma protein(s). The ratio of blood cinacalcet

concentration to plasma cinacalcet concentration is 0.80 at a blood cinacalcet concentration of

10 ng/mL.

Metabolism and Excretion

Cinacalcet is metabolized by multiple enzymes, primarily CYP3A4, CYP2D6, and CYP1A2. After

administration of a 75 mg radiolabeled dose to healthy volunteers, cinacalcet was metabolized via: 1)

oxidative N-dealkylation to hydrocinnamic acid and hydroxy-hydrocinnamic acid, which are further

metabolized via β-oxidation and glycine conjugation; the oxidative N-dealkylation process also

generates metabolites that contain the naphthalene ring; and 2) oxidation of the naphthalene ring on the

parent drug forming dihydrodiols, which are further conjugated with glucuronic acid. The plasma

concentrations of the major circulating metabolites, including the cinnamic acid derivatives and

glucuronidated dihydrodiols, markedly exceed the parent drug concentrations. The hydrocinnamic acid

metabolite and glucuronide conjugates have minimal or no calcimimetic activity. Renal excretion of

metabolites was the primary route of elimination of radioactivity. Approximately 80% of the dose was

recovered in the urine and 15% in the feces.

Specific Populations

Age: Geriatric Population

The pharmacokinetic profile of cinacalcet in geriatric patients (age ≥ 65 years, n = 12) is similar to that

for patients who are < 65 years of age (n = 268) [see Use in Specific Populations (8.5)].

Hepatic Impairment

The disposition of a 50 mg Sensipar single dose was compared between patients with hepatic

impairment and patients with normal hepatic function. Cinacalcet exposure (AUC -

) was

comparable between healthy volunteers and patients with mild hepatic impairment. However, in patients

with moderate and severe hepatic impairment (as indicated by the Child-Pugh method), cinacalcet

exposures (AUC -

) were 2.4 and 4.2 fold higher, respectively, than that in healthy volunteers.

The mean half-life of cinacalcet increased from 49 hours in healthy volunteers to 65 hours and 84

hours in patients with moderate and severe hepatic impairment, respectively. Protein binding of

cinacalcet is not affected by impaired hepatic function [see Use in Specific Populations (8.7)].

Renal Impairment

The pharmacokinetic profile of a 75 mg Sensipar single dose in patients with mild, moderate, and severe

renal impairment, and those on hemodialysis or peritoneal dialysis is comparable with that in healthy

volunteers [see Use in Specific Populations (8.6)].

Drug Interactions

In vitro studies indicate that cinacalcet is a strong inhibitor of CYP2D6, but not an inhibitor of CYP1A2,

CYP2C9, CYP2C19, and CYP3A4. In vitro induction studies indicate that cinacalcet is not an inducer of

CYP450 enzymes. Tables 5 and 6 list the findings from in vivo drug-drug interaction studies.

Table 5. Effect of co-administered drugs on cinacalcet

Co-administered drug and dosing

regimen

Cinacalcet

Dos e*

Mean change

in

AUC

Mean change in

C

200 mg ketoconazole twice daily for

7 days

90 mg on day 5

↑127%

↑116%

1500 mg calcium carbonate, single

dose

100 mg

↓6%

↓5%

80 mg pantoprazole daily for 3 days

90 mg on day 3

↑1%

↓3%

2400 mg sevelamer HCl three times a

day for 2 days

90 mg on day 1 with

first

dose of sevelamer

↓4%

↓7%

*Single dose.

Table 6. Effect of cinacalcet co-administration on other drugs

(0 infinite )

(0 infinite )

(0 -inf)

max

Cinacalcet dosing

regimen

Co-administered drug

Name and Dose

Mean change in

AUC

Mean change in C

30 mg twice daily for

8 days

25 mg warfarin*

tablet

↑1% for R-warfarin

↓1% for S-warfarin

↓10% for R-warfarin

↓12% for S-warfarin

90 mg daily for 7 days to

CYP2D6 extensive

metabolizers

50 mg desipramine

↑264%

↑75%

90 mg daily for 5 days

2 mg midazolam

↑5%

↓5%

25 or 100 mg single dose

to CYP2D6 extensive

metabolizers

50 mg amitriptyline

single dose

↑21-22% for

amitriptyline

↑17-23% for

nortriptyline

↑13-21% for

amitriptyline

↑11-15% for

nortriptyline

*No significant change in prothrombin time.

Single dose on day 5.

Nortriptyline is an active metabolite of amitriptyline.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity

Standard lifetime dietary carcinogenicity bioassays were conducted in mice and rats. Mice were given

cinacalcet at dietary doses of 15, 50, and 125 mg/kg/day in males and 30, 70, and 200 mg/kg/day in

females (exposures up to 2 times those resulting with a human oral dose of 180 mg/day based on AUC

comparison). Rats were given dietary doses of 5, 15, and 35 mg/kg/day in males and 5, 20, and

35 mg/kg/day in females (exposures up to 2 times those resulting with a human oral dose of 180 mg/day

based on AUC comparison). No increased incidence of tumors was observed following treatment with

cinacalcet.

Mutagenicity

Cinacalcet was not genotoxic in the Ames bacterial mutagenicity assay, nor in the Chinese Hamster

Ovary (CHO) cell HGPRT forward mutation assay and CHO cell chromosomal aberration assay, with

and without metabolic activation, nor in the in vivo mouse micronucleus assay.

Impairment of Fertility

Female rats were given oral gavage doses of 5, 25, and 75 mg/kg/day cinacalcet beginning 2 weeks

before mating and continuing through gestation day 7. Male rats were given oral doses 4 weeks prior to

mating, during mating (3 weeks) and 2 weeks postmating. No effects were observed in male or female

fertility at 5 and 25 mg/kg/day (exposures up to 3 times those resulting with a human oral dose of

180 mg/day based on AUC comparison). At 75 mg/kg/day, there were slight adverse effects (slight

decreases in body weight and food consumption) in males and females.

14 CLINICAL STUDIES

14.1 Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease on Dialysis

Three 6-month, multicenter, randomized, double-blind, placebo-controlled clinical studies of similar

design were conducted in patients with CKD on dialysis. A total of 665 patients were randomized to

Sensipar and 471 patients to placebo. The mean age of the patients was 54 years, 62% were male, and

52% were Caucasian. The average baseline iPTH level by the Nichols IRMA was 712 pg/mL, with

26% of the patients having a baseline iPTH level > 800 pg/mL. The mean baseline Ca x P product was

61 mg /dL . The average duration of dialysis prior to study enrollment was 67 months. Ninety-six

percent of patients were on hemodialysis and 4% on peritoneal dialysis. At study entry, 66% of the

patients were receiving vitamin D sterols and 93% were receiving phosphate binders. Sensipar (or

placebo) was initiated at a dose of 30 mg once daily and titrated every 3 or 4 weeks to a maximum dose

of 180 mg once daily to achieve an iPTH of ≤ 250 pg/mL. The dose was not increased if a patient had

any of the following: iPTH ≤ 200 pg/mL, serum calcium < 7.8 mg/dL, or any symptoms of

hypocalcemia. If a patient experienced symptoms of hypocalcemia or had a serum calcium < 8.4 mg/dL,

calcium supplements and/or calcium-based phosphate binders could be increased. If these measures

were insufficient, the vitamin D dose could be increased. Approximately 70% of patients in the Sensipar

arm and 80% of the patients in the placebo arm completed the 6-month studies. In the primary efficacy

analysis, 40% of the patients on Sensipar and 5% of placebo-treated patients achieved an iPTH

≤ 250 pg/mL (p < 0.001) (Table 7, Figure 1). These studies showed that Sensipar reduced iPTH while

lowering Ca x P, calcium, and phosphorus levels (Table 7, Figure 2). The median dose of Sensipar at

the completion of the studies was 90 mg. Patients with milder disease typically required lower doses.

(0 -inf)

max

Similar results were observed when either the iPTH or biointact PTH (biPTH) assay was used to

measure PTH levels in CKD patients on dialysis; treatment with cinacalcet did not alter the relationship

between iPTH and biPTH.

Table 7. Effects of Sensipar on iPTH, Ca x P, Serum Calcium, and Serum Phosphorus in

6-month Phase 3 Studies (Patients on Dialysis)

Study 1

Study 2

Study 3

Placebo

Sens ipar

Placebo Sens ipar Placebo

Sens ipar

(n = 205)

(n = 205)

(n = 165) (n = 166)

(n = 101)

(n = 294)

iPTH

Baseline (pg/mL): Median

Mean

(SD)

651 (398)

636 (341)

(317)

652 (372)

832 (486)

(685)

Evaluation Phase (pg/mL)

Median Percent Change

+3.8

-48.3

+8.4

-54.1

+2.3

-48.2

Patients Achieving Primary

Endpoint (iPTH

≤ 250 pg/mL) (%)

41%**

46%**

35%**

Patients Achieving ≥ 30%

Reduction in iPTH (%)

Patients Achieving iPTH

≤ 250 pg/mL and Ca x P

< 55 mg /dL (%)

Ca x P

Baseline (mg /dL )

Evaluation Phase (mg /dL )

Median Percent Change

-2.0

-14.9

-3.1

-19.7

-4.8

-15.7

Calcium

Baseline (mg/dL)

10.0

Evaluation Phase (mg/dL)

10.0

Median Percent Change

+0.5

-5.5

+0.1

-7.4

+0.3

-6.0

Phosphorus

Baseline (mg/dL)

Evaluation Phase (mg/dL)

Median Percent Change

-1.0

-9.0

-2.4

-12.4

-5.6

-8.6

** p < 0.001 compared with placebo; p-values presented for primary endpoint only.

iPTH value based on averaging over the evaluation phase (defined as weeks 13 to 26 in

studies 1 and 2 and weeks 17 to 26 in study 3).

Values shown are medians unless indicated otherwise.

Figure 1. Mean (SE) iPTH Values (Pooled Phase 3 Studies)

Data are presented for patients who completed the studies; Placebo (n = 342), Sensipar (n = 439).

Figure 2. Mean (SE) Ca x P Values (Pooled Phase 3 Studies)

Data are presented for patients who completed the studies; Placebo (n = 342), Sensipar (n = 439).

Reductions in iPTH and Ca x P were maintained for up to 12 months of treatment.

Sensipar decreased iPTH and Ca x P levels regardless of disease severity (i.e., baseline iPTH value),

duration of dialysis, and whether or not vitamin D sterols were administered. Approximately 60% of

patients with mild (iPTH ≥ 300 to ≤ 500 pg/mL), 41% with moderate (iPTH > 500 to 800 pg/mL), and

11% with severe (iPTH > 800 pg/mL) secondary HPT achieved a mean iPTH value of ≤ 250 pg/mL.

Plasma iPTH levels were measured using the Nichols IRMA.

14.2 Parathyroid Carcinoma

Twenty-nine patients with Parathyroid Carcinoma were enrolled in a single-arm, open-label study. The

study consisted of two phases, a dose-titration phase and a maintenance phase. Patients initially received

30 mg cinacalcet twice daily and then were titrated every 2 weeks to a maximum dose of 90 mg four

times daily. Dosage escalation during the variable-length (2 to 16 weeks) titration phase continued until

the serum calcium concentration was ≤ 10 mg/dL (2.5 mmol/L), the patient reached the highest possible

dosage, or adverse events precluded further dosage increases.

Twenty-nine patients entered the study. The median exposure to cinacalcet was 229 days (range: 1 to

1051). At baseline the mean (SE) serum calcium was 14.1 (0.4) mg/dL. At the end of the titration phase,

the mean (SE) serum calcium was 12.4 (0.5) mg/dL, which is a mean reduction of 1.7 (0.6) mg/dL from

baseline. Figure 3 illustrates mean serum calcium (mg/dL) over time for all patients still on study at each

time point from the beginning of titration to study visit week 80. Daily dose during the study ranged

from 30 mg twice daily to 90 mg four times daily.

Figure 3. Serum Calcium Values in Patients with Parathyroid Carcinoma Receiving Sensipar at

Baseline, Titration, and Maintenance Phase

n = Number of patients with non-missing values at the timepoint.

End of Titration (EOT) phase could occur at any visit from week 2 to 16. Patients at EOT are those

who completed titration.

14.3 Patients with Hypercalcemia Due to Primary Hyperparathyroidism

Seventeen patients with severe hypercalcemia due to primary HPT, who had failed or had

contraindications to parathyroidectomy, participated in an open-label, single-arm study. The study

consisted of two phases, a dose-titration phase and a maintenance phase. In this trial, severe

hypercalcemia was defined as a screening serum calcium level of > 12.5 mg/dL. Patients initially

received 30 mg cinacalcet twice daily and then were titrated every 2 weeks to a maximum dose of

90 mg 4 times daily. Dosage escalation during the variable-length (2 to 16 weeks) titration phase

continued until the serum calcium concentration was ≤ 10 mg/dL (2.5 mmol/L), the patient reached the

highest possible dosage, or adverse events precluded further dosage increases.

Seventeen patients entered the study. The median exposure to cinacalcet was 270 days (range: 32 to

1,105). At baseline the mean (SE) serum calcium was 12.7 (0.2) mg/dL. At the end of the titration phase

the mean (SE) serum calcium was 10.4 (0.3) mg/dL, which is a mean reduction of 2.3 (0.3) mg/dL from

baseline. Figure 4 illustrates mean serum calcium (mg/dL) over time for all patients still on study at each

time point from the beginning of titration to study visit week 80. Daily dose during the study ranged

from 30 mg twice a day to 90 mg four times a day.

Figure 4. Mean Serum Calcium (SE) at Baseline, End of Titration, and Scheduled Maintenance

Visits (Patients with Severe intractable primary HPT)

n = Number of patients with non-missing values at the timepoint.

End of Titration (EOT) phase could occur at any visit from week 2 to 16. Patients at EOT are those

who completed titration.

Sixty-seven patients with primary HPT who met criteria for parathyroidectomy on the basis of

corrected total serum calcium (> 11.3 mg/dL [2.82 mmol/L] and ≤ 12.5 mg/dL [3.12 mmol/L]), but who

were unable to undergo parathyroidectomy participated in a randomized, double-blind, placebo-

controlled study. A total of 33 patients were randomized to Sensipar and 34 patients randomized to

placebo. The mean age of the patients was 72 years, 52% were female, 61% were Caucasian, and 5%

were Blacks. The study started with a 12-week titration phase, followed by a 16-week efficacy-

assessment phase. Cinacalcet was initiated at a dose of 30 mg twice daily and titrated to maintain a

corrected total serum calcium concentration within the normal range. During the efficacy period a

significantly higher percentage of cinacalcet-treated patients compared with the placebo-treated patients

achieved mean corrected total serum calcium concentration (≤ 10.3 mg/dL [2.57 mmol/L], 75.8% vs 0%,

p < 0.001) and ≥ 1 mg/dL [0.25 mmol/L] decrease from baseline in mean corrected total serum calcium

concentration (84.8% vs 5.9%, p < 0.001). The median dose of Sensipar at the completion of the study

was 60 mg/day.

16 HOW SUPPLIED/STORAGE AND HANDLING

Product: 50090-4470

NDC: 50090-4470-0 30 TABLET, COATED in a BOTTLE, PLASTIC

17 PATIENT COUNSELING INFORMATION

Hypocalcemia: Advise patients to report symptoms of hypocalcemia, including paresthesias,

myalgias, muscle spasms, and seizures, to their healthcare provider [see Warnings and Precautions

(5.1)].

Upper Gastrointestinal Bleeding: Advise patients to report any symptoms of upper gastrointestinal

bleeding to their health care provider [see Warnings and Precautions (5.2)].

Heart Failure: Advise patients with heart failure that use of Sensipar may worsen their heart failure

and additional monitoring may be required [see Warnings and Precautions (5.3)].

Advise patients to report nausea and vomiting to their health care provider [see Adverse Reactions

(6.1)].

Advise patients to take Sensipar with food or shortly after a meal and to take the tablets whole and

not divide them [see Dosage and Administration (2.1)].

Inform patients of the importance of regular blood tests, in order to monitor the safety and efficacy

of Sensipar therapy.

Sensipar

(cinacalcet) Tablets

Manufactured by:

Amgen Inc.

One Amgen Center Drive

Thousand Oaks, California 91320-1799

Patent: http://pat.amgen.com/sensipar/

© 2004-2019 Amgen Inc. All rights reserved.

www.sensipar.com

1-800-77-AMGEN (1-800-772-6436)

1xxxxxx – v13

Storage

Store at 25°C (77°F); excursions permitted from 15°C to 30°C (59°F to 86°F). [See USP controlled

room temperature].

cinacalcet hydrochloride

SENSIPAR

cinacalcet hydrochloride tablet, coated

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:50 0 9 0 -4470 (NDC:55513-0 73)

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

CINACALCET HYDRO CHLO RIDE (UNII: 1K8 6 0 WSG25) (CINACALCET - UNII:UAZ6 V7728 S)

CINACALCET

30 mg

Inactive Ingredients

Ingredient Name

Stre ng th

CARNAUBA WAX (UNII: R12CBM0 EIZ)

MICRO CRYSTALLINE CELLULO SE (UNII: OP1R32D6 1U)

CRO SPO VIDO NE, UNSPECIFIED (UNII: 2S78 30 E56 1)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

PO VIDO NE, UNSPECIFIED (UNII: FZ9 8 9 GH9 4E)

STARCH, CO RN (UNII: O8 232NY3SJ)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

Product Characteristics

Color

GREEN (light green)

S core

no sco re

S hap e

OVAL

S iz e

10 mm

Flavor

Imprint Code

AMG;30

Contains

Packag ing

#

Item Code

Package Description

Marketing Start

Date

Marketing End

Date

1

NDC:50 0 9 0 -4470 -

30 in 1 BOTTLE, PLASTIC; Type 0 : No t a Co mbinatio n

Pro duc t

0 8 /19 /20 19

A-S Medication Solutions

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 216 8 8

0 4/0 4/20 0 4

Labeler -

A-S Medication Solutions (830016429)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

A-S Medicatio n So lutio ns

8 30 0 16 429

RELABEL(50 0 9 0 -4470 )

Revised: 8/2019

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