Cinacalcet Hydrochloride 90 mg Tablet, 250-count
Other active recalls for Cinacalcet (different manufacturers) — 6 · tap to view
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Calcium-sensing Receptor Agonist class.
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🏭 Manufacturer & labeler
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🩺 Clinical
- Cinacalcet helps control a hormone called PTH (parathyroid hormone) that your parathyroid glands produce. When PTH gets too high — which is common in kidney disease or certain para...
- Why did my doctor prescribe cinacalcet — what exactly does it do?
- Yes, timing and how you take it both matter. Always take cinacalcet with food or right after a meal — food helps your body absorb much more of the medication. Never chew, crush, or...
- Does it matter when I take cinacalcet, and can I split or crush the tablet?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Cinacalcet — tap one for details:
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Cinacalcet 90 mg 47335-0600-83 | Sun | 30 tablets | $0.918 | — | FDA listed | — |
| Cinacalcet 90 mg 16729-0442-10 | Accord | 30 tablets | $1.000 | AB | Availability likely | — |
| Cinacalcet 90 mg 31722-0105-30 | Camber | 30 tablets | $1.037 | — | Availability likely | — |
| Cinacalcet 90 mg 64380-0885-04 | Strides | 30 tablets | $1.037 | AB | Availability likely | — |
| Cinacalcet 90 mg 69097-0412-02 | Cipla | 30 tablets | $1.037 | AB | Availability likely | — |
| Cinacalcet 90 mg 76282-0676-30 | EXELAN | 30 tablets | $1.037 | AB | Availability likely | — |
| Sensipar 90 mg 55513-0075-30 | Amgen | 30 tablets | — | — | FDA listed | — |
| Cinacalcet 90 mg 63629-8765-01 | Bryant | 30 tablets | — | AB | Discontinued | — |
| Cinacalcet 90 mg 63629-9606-01 | Bryant | 30 tablets | — | AB | FDA listed | — |
| Cinacalcet Hydrochloride 90 mgthis 65162-0213-25 | Amneal | 250 tablets | — | — | FDA listed | — |
| Cinacalcet 90 mg 65862-0833-01 | Aurobindo | 100 tablets | — | AB | Discontinued | — |
| Cinacalcet 90 mg 67877-0505-01 | Ascend | 100 tablets | — | AB | FDA listed | — |
| Cinacalcet 90 mg 71335-2763-01 | Bryant | 30 tablets | — | AB | FDA listed | — |
| Cinacalcet 90 mg 72162-1845-03 | Bryant | 30 tablets | — | AB | FDA listed | — |
| Cinacalcet 90 mg 72162-2527-03 | Bryant | 30 tablets | — | AB | FDA listed | — |
| Cinacalcet 90 mg 72865-0152-30 | XLCare | 30 tablets | — | — | FDA listed | — |
| Cinacalcet 90 mg 84386-0113-01 | Aurobindo | 100 tablets | — | AB | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 65162-0213-03 | 30 TABLET in 1 BOTTLE (65162-213-03) | 2021-12-06 | Active |
| 65162-0213-10 | 100 TABLET in 1 BOTTLE (65162-213-10) | 2021-12-06 | Active |
| 65162-0213-25 You're viewing this | 250 TABLET in 1 BOTTLE (65162-213-25) | 2021-12-06 | Active |
You're viewing the largest of 3 pack sizes for this product.
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🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope. |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Cinacalcet tablets are 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) Limitations of Use: Cinacalcet tablets are 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)
1.1Secondary Hyperparathyroidism Cinacalcet tablets are 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: Cinacalcet tablets are 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) ] .
1.2Parathyroid Carcinoma Cinacalcet tablets are indicated for the treatment of hypercalcemia in adult patients with Parathyroid Carcinoma [see Clinical Studies (14.2) ] .
1.3Primary Hyperparathyroidism Cinacalcet tablets are 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) ] .
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Cinacalcet 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 mg, 60 mg, 90 mg, 120 mg, 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. (2.5)
2.1Administration Cinacalcet tablets should be taken with food or shortly after a meal. Cinacalcet tablets are administered orally and should always be taken whole and not chewed, crushed, or divided.
2.2Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease on Dialysis The recommended starting oral dose of cinacalcet tablets 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 cinacalcet tablets [see Dosage and Administration (2.3) ] . Cinacalcet tablets should be titrated no more frequently than every 2 to 4 weeks through sequential doses of 30 mg, 60 mg, 90 mg, 120 mg, 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 cinacalcet tablets. Cinacalcet tablets 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 cinacalcet tablets [see Dosage and Administration (2.3) and Warnings and Precautions (5.1) ] .
2.3Patients with Parathyroid Carcinoma and Primary Hyperparathyroidism The recommended starting oral dose of cinacalcet tablets is 30 mg twice daily. The dose of cinacalcet tablets 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 cinacalcet tablets [see Dosage and Administration (2.5) and Warnings and Precautions (5.1) ] .
2.4Switching from Parsabiv (etelcalcetide) to Cinacalcet Tablets Discontinue etelcalcetide for at least 4 weeks prior to starting cinacalcet tablets. Ensure corrected serum calcium is at or above the lower limit of normal prior to cinacalcet tablets initiation [see Warnings and Precautions (5.1)] . Initiate cinacalcet tablets treatment at a starting dose of 30 mg once daily.
2.5Monitoring 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 h…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS 30 mg tablets (green color, coated, oval-shaped tablets, debossed with “155” on one side and plain on the other side) 60 mg tablets (green color, coated, oval-shaped tablets, debossed with “157” on one side and plain on the other side) 90 mg tablets (green color, coated, oval-shaped tablets, debossed with “213” on one side and plain on the other side) Tablets: 30 mg, 60 mg, and 90 mg tablets (3)
⛔ Contraindications ▾
4 CONTRAINDICATIONS Cinacalcet HCl treatment initiation is contraindicated if serum calcium is less than the lower limit of the normal range [see Warnings and Precautions (5.1) ] . Cinacalcet hydrochloride treatment initiation is contraindicated if serum calcium is less than the lower limit of the normal range. (4, 5.1)
⚠️ Warnings and Cautions ▾
5 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.
(2.5 , 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)
5.1Hypocalcemia Cinacalcet HCl 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 cinacalcet HCl, including in pediatric patients.
The safety and effectiveness of cinacalcet HCl have not been established in pediatric patients [see Pediatric Use (8.4) ] . Cinacalcet HCl 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 cinacalcet HCl have not been established.
Clinical studies indicate that cinacalcet HCl-treated patients with CKD not on dialysis have an increased risk for hypocalcemia compared with cinacalcet HCl-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 cinacalcet HCl-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 cinacalcet HCl. 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 cinacalcet HCl.
Closely monitor corrected serum calcium and QT interval in patients at risk receiving cinacalcet HCl. Seizures In clinical studies, seizures (primarily generalized or tonic-clonic) were observed in 1.4% (43/3049) of cinacalcet HCl-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 cinacalcet HCl. Concurrent Administration with Other Calcium-Lowering Drug Products Concurrent administration of cinacalcet HCl with calcium-lowering drugs including other calcium-sensing receptor agonists could result in severe hypocalcemia. Closely monitor serum calcium in patients receiving cinacalcet HCl 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 ca…
🤒 Adverse Reactions ▾
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) ] The most common adverse reactions (i.e., ≥ 25%) associated with cinacalcet hydrochloride were nausea and vomiting. (6) To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical 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 cinacalcet HCl, 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 cinacalcet HCl-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 (n = 470) Cinacalcet HCl (n = 656) Event*: (%) (%) Nausea 19 31 Vomiting 15 27 Diarrhea 20 21 Myalgia 14 15 Dizziness 8 10 Hypertension 5 7 Asthenia 4 7 Anorexia 4 6 Pain Chest, Non-Cardiac 4 6 Dialysis Access Site Infection 4 5 *Included are events that were reported at a greater incidence in the cinacalcet HCl group than in the placebo group. In a randomized, double-blind placebo-controlled study of 3,883 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 HCl group), the most frequently reported adverse reactions (incidence of ≥ 5% in the Cinacalcet HCl 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 1 Placebo (N=1923) Cinacalcet HCl (N=1938) 3,699 subject-years 4,044 subject-years Percent of subjects reporting Adverse Reactions (%) 90.9
93.2Nausea 15.5
29.1Vomiting 13.7
25.6Diarrhea 18.7
20.5Dyspnea 11.5
13.4Cough 9.8
11.7Hypotension 10.5
11.6Headache 9.6
11.5Hypocalcaemia 1.4
11.2Muscle spasms 9.2
11.1Abdominal pain 9.6
10.9Abdominal pain upper 6.3
8.2Hyperkalemia 6.1
8.1Upper respiratory tract infection 6.3
7.6Dyspepsia 4.6
7.4Dizziness 4.7
7.3Decreased appetite 3.5
5.9Asthenia 3.8
5.4Constipation 3.8 5 1 Adverse reactions that occurred in ≥ 5% Frequency in the cinacalcet HCl 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 cinacalcet HCl 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 cinacalcet HCl in these patient populations is generally consistent with that seen in patients with CKD on dialysis. Forty six patients were treated with cinacalcet HCl 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…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Co-administration with a strong CYP3A4 inhibitor may increase serum levels of cinacalcet. Dose adjustment and monitoring of iPTH serum phosphorous 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)
7.1Strong CYP3A4 Inhibitors Cinacalcet is partially metabolized by CYP3A4. Dose adjustment of cinacalcet HCl 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) ] .
7.2CYP2D6 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) ] .
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pediatric Use: A fatal outcome was reported in a pediatric clinical trial patient with severe hypocalcemia. Cinacalcet hydrochloride is not indicated for use in pediatric patients. ( 8.4 ).
8.1Pregnancy Risk Summary Limited case reports of cinacalcet HCl 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 to 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% to 4% and 15% to 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.
8.2Lactation Risk Summary There are no data regarding the presence of cinacalcet HCl 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 cinacalcet HCl and any potential adverse effects on the breastfed infant from cinacalcet HCl or from the underlying maternal condition.
8.4Pediatric Use The safety and efficacy of cinacalcet HCl have not been established in pediatric patients. The use of cinacalcet HCl 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 cinacalcet HCl 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 cinacalcet HCl.
Dosing with cinacalcet HCl in Pediatric Study 1 was stopped because of a fatality in a cinacalcet HCl-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 cinacalcet HCl to the death could not be excluded [see Warnings and Precautions (5.1) ] .
Study 1 was terminated and changes to cinacalcet HCl dosing after…
🆘 Overdosage ▾
10 OVERDOSAGE Overdosage of Cinacalcet HCl 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 cinacalcet HCl is highly protein bound, hemodialysis is not an effective treatment for overdosage of cinacalcet HCl.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism 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 cinacalcet tablets, is a calcimimetic agent that directly lowers PTH levels by increasing the sensitivity of the calcium-sensing receptor to activation by extracellular calcium. The reduction in PTH is associated with a concomitant decrease in serum calcium levels.
12.2Pharmacodynamics 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 max ) 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.
12.3Pharmacokinetics Absorption and Distribution After oral administration of cinacalcet, C max is achieved in approximately 2 to 6 hours. Cinacalcet C max and AUC (0-infinite) were increased by 82% and 68%, respectively, following administration with a high-fat meal compared with fasting in healthy volunteers. The C max and AUC (0-infinite) 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 approximately 6 hours and a 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 max of cinacalcet increase proportionally over the dose range of 30 mg to 180 mg once daily. The pharmacokinetic profile of cinacalcet does not change over time with once daily dosing of 30 mg 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 cinacalcet HCl single dose was compared between patients with hepatic impairment and patients with normal hepatic function. Cinacalcet exposure (AUC (0-inf…
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Cinacalcet tablets, 30 mg are formulated as green color, film-coated, oval-shaped tablets debossed with “155” on one side and plain on the other side. They are available as follows: Bottles of 30: NDC 65162-155-03 Bottles of 100: NDC 65162-155-10 Bottles of 250: NDC 65162-155-25 Cinacalcet tablets, 60 mg are formulated as green color, film-coated, oval-shaped tablets debossed with “157” on one side and plain on the other side. They are available as follows: Bottles of 30: NDC 65162-157-03 Bottles of 100: NDC 65162-157-10 Bottles of 250: NDC 65162-157-25 Cinacalcet tablets, 90 mg are formulated as green color, film-coated, oval-shaped tablets debossed with “213” on one side and plain on the other side.
They are available as follows: Bottles of 30: NDC 65162-213-03 Bottles of 100: NDC 65162-213-10 Bottles of 250: NDC 65162-213-25 Storage Store at 20º to 25ºC (68º to 77ºF); excursions permitted between 15° to 30ºC (59° to 86ºF) [see USP Controlled Room Temperature].
📋 Description ▾
11 DESCRIPTION Cinacalcet tablets contain the hydrochloride salt of the active ingredient cinacalcet, a positive modulator of the calcium sensing receptor. The empirical formula for cinacalcet is C 22 H 22 F 3 N⋅HCl 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. 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: Cinacalcet tablets are formulated as green color, 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).
Inactive Ingredients The following are the inactive ingredients in cinacalcet tablets: colloidal silicon dioxide, crospovidone, D&C Yellow #10 aluminum lake, FD&C Blue #2/Indigo carmine aluminum lake, hypromellose, magnesium stearate, mannitol, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, pregelatinized starch (corn), talc, and titanium dioxide. a7c316fa-figure-01
💬 Information for Patients ▾
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 cinacalcet HCl 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 cinacalcet HCl 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 cinacalcet HCl therapy.
Distributed by: Amneal Pharmaceuticals LLC Bridgewater, NJ 08807 Rev. 08-2021-00