What is cinacalcet used for. Cinacalcet: A Comprehensive Guide to Its Uses, Mechanisms, and More

22.07.202303.07.2023 by alexxlab

What is cinacalcet used for? How does it work? What are the potential adverse effects? Get answers to these questions and more in this detailed overview.

Содержание

Indications for Cinacalcet

Cinacalcet is a medication primarily used to manage and treat the following conditions:

Secondary hyperparathyroidism in patients with end-stage kidney disease
Primary hyperparathyroidism in individuals who are not surgical candidates or for whom surgery would be high-risk
Calciphylaxis in patients with advanced kidney disease or on dialysis

In chronic kidney disease, patients often have high phosphorus levels, variable calcium levels, and increased parathyroid hormone (PTH) levels. Cinacalcet helps reduce the serum PTH level and restore calcium levels within the target ranges defined by the Kidney Disease Outcomes Quality Initiative (K-DOQI).

Mechanism of Action

Cinacalcet is classified as a “calcimimetic,” meaning it acts on the calcium-sensing receptors (CaSR) located on the chief cells of the parathyroid gland. CaSR detects minor changes in extracellular calcium levels and maintains the PTH level accordingly through PTH gene transcription and parathyroid cell growth.

When cinacalcet activates the CaSR, it leads to the inhibition of cAMP accumulation and the stimulation of the phosphoinositide-phospholipase C pathway. This results in increased intracellular calcium levels and the suppression of PTH secretion, effectively lowering the PTH level.

Adverse Effects of Cinacalcet

What are the possible adverse effects associated with cinacalcet? The most common side effects include:

Nausea and vomiting
Diarrhea
Decreased appetite
Muscle spasms
Hypocalcemia

Clinicians should closely monitor patients receiving cinacalcet for these potential adverse events and make appropriate adjustments to the dosage or treatment plan as needed.

Monitoring and Dosing Considerations

What should healthcare providers consider when monitoring patients on cinacalcet therapy? Key considerations include:

Regular monitoring of serum calcium, phosphorus, and PTH levels
Adjusting the cinacalcet dose as needed to maintain target laboratory values
Monitoring for signs and symptoms of hypocalcemia, which may require dose reduction or calcium supplementation
Considering the use of cinacalcet in combination with other therapies, such as oral phosphorus binders and vitamin D analogs, to optimize treatment

Cinacalcet in Pediatric Populations

Cinacalcet has also been used in the treatment of children and adolescents with chronic kidney disease and associated renal osteodystrophy, known as CKD-mineral and bone disorders (CKD-MBD). In these cases, cinacalcet helps lower the parathyroid hormone level and treat hypercalcemia, while other therapies address hyperphosphatemia.

Off-Label Uses of Cinacalcet

While cinacalcet’s primary indications are for the management of secondary and primary hyperparathyroidism, it has also been used in other scenarios, such as:

Treating hypercalcemia in patients with parathyroid carcinoma
Potentially as a therapeutic option in patients where surgical removal of a parathyroid mass is not feasible

However, it’s important to note that the use of cinacalcet in these off-label scenarios may not be as well-established or supported by robust clinical evidence.

Interprofessional Strategies for Optimal Care

To ensure the best possible outcomes for patients receiving cinacalcet, an interprofessional approach is recommended, involving:

Effective communication and coordination among healthcare team members, including physicians, pharmacists, nurses, and other relevant providers
Educating patients on the proper use of cinacalcet, potential side effects, and the importance of adhering to the prescribed regimen
Monitoring patients closely for adverse events and making timely adjustments to the treatment plan as needed
Collaboration among the healthcare team to address any challenges or concerns that may arise during the course of treatment

Cinacalcet – StatPearls – NCBI Bookshelf

Syeda Zeenat S. Junaid; Jayesh B. Patel.

Author Information and Affiliations

Last Update: August 12, 2022.

Continuing Education Activity

Cinacalcet is a medication used in the management and treatment of secondary hyperparathyroidism (on dialysis population), primary hyperparathyroidism for which the patient may not be a surgical candidate, and the treatment of calciphylaxis in patients with advanced kidney disease or on dialysis. It belongs to the calcimimetic class of medications. This activity reviews the indications, action, and contraindications for cinacalcet as a valuable agent in treating the conditions mentioned above. This activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) pertinent for members of the healthcare team in the care of patients with hyperparathyroidism and related conditions.

Objectives:

Identify the mechanism of action of cinacalcet.
Describe the possible adverse effects of cinacalcet
Review the appropriate monitoring for patients receiving therapy with cinacalcet
Outline some interprofessional team strategies for improving care coordination and communication to advance knowledge regarding the side effects of cinacalcet and improve outcomes.

Access free multiple choice questions on this topic.

Indications

Cinacalcet hydrochloride classifies as a “calcimimetic.” Its primary indication is to reduce the parathyroid hormone level in patients with secondary hyperparathyroidism associated with end-stage kidney disease. In chronic kidney disease, patients often have high phosphorus levels, variable calcium levels, and increased parathyroid hormone levels (>300 pg/mL).[1] The role of the cinacalcet in this condition is to reduce the serum parathyroid hormone level and prevent bone destruction. This intervention reinstates the calcium levels within the target ranges defined by the Kidney Disease Outcomes Quality Initiative (K-DOQI) for disease management.[2] It reduces the chances of requiring a parathyroidectomy for secondary hyperparathyroidism. Clinicians often use this medication in combination therapy with an oral phosphorous binder (calcium acetate, sevelamer) as well as vitamin D analogs (calcitriol, paricalcitol).[1][3]

Cinacalcet can be used for the treatment of primary hyperparathyroidism in the individual who is not a surgical candidate or in whom surgery would be high risk.[4] Because cinacalcet lowers PTH and reduces serum calcium levels, it can be used along with bisphosphonates to reduce calcium resorption from bone.

Cinacalcet is often a part of the treatment modality in individuals with calciphylaxis, which can present in the patient with end-stage kidney disease.[5] It is being used increasingly in pediatric populations with CKD and suffering from concomitant renal osteodystrophy, described as CKD–mineral and bone disorders (CKD–MBD). An important part of the management of this condition is lowering the parathyroid hormone level and treating hypercalcemia with cinacalcet, as well as treating hyperphosphatemia with a non-calcium-based phosphorus binder. Cinacalcet, when combined with other treatments for calciphylaxis, has shown improved efficacy in treating this condition.[5]

Clinicians can also use this medication has also been used to treat hypercalcemia in patients with parathyroid carcinoma. While the treatment of parathyroid carcinoma is primarily surgical, therapy with cinacalcet does help reduce the serum calcium level.[6] It may also be a therapeutic option in patients in whom surgical removal of the mass is deemed futile.[7]

Mechanism of Action

Cinacalcet is a “calcimimetic,” meaning that it acts on the calcium-sensing receptors (CaSR) located on the chief cells of the parathyroid gland.[8] CaSR detects a minor change in the extracellular calcium level and maintains the PTH level accordingly. [8] This process occurs through PTH gene transcription and parathyroid cell growth. The CaSR couples with a 7-transmembrane domain G-proteins. On the chief cells, the predominant forms are Gi and Gq. Once activated, cAMP accumulation becomes inhibited, and simultaneously the phosphoinositide-phospholipase C pathway gets stimulated. The ensuing increase in IP3 and DAG levels leads to intracellular calcium influx. The end result of this the Gq pathway is specifically dominant-negative, i.e., suppression of PTH secretion. Disruption of this cascade has also been present in various etiologies of hyperparathyroidism.[9]

“Calcimimetic” medications, as the name suggests, may not be the real calcium ligands, but they activate these receptors and utilize the Gq/Gi pathways to establish the negative feedback loop to raise calcium levels. This feedback occurs through the suppression of both the production of PTH and its secretion and ultimately leads to the mitigation of calcium and phosphorus products in the blood. [10]

Administration

This medication is to be taken once daily with food. Most therapies directed at the endocrine axis should preferably be taken at the same time every day. Food has a positive effect on cinacalcet’s absorption, increasing its levels in the plasma by more than three-fold compared to when taking it without food.[11] It has a long half-life of approximately 1.5 days. It is highly bound to plasma proteins, metabolized primarily in the liver, and is dependent on the kidney for excretion.[11]

The dosage schedules are adapted according to the PTH response individually in patients. The pediatric population may warrant reduced dosages because of their lower body surface area and the changed CYP profiles.[2]

Adverse Effects

The common side effects are nausea and vomiting.[7] It can occur in up to one-third of patients taking this medication. Dizziness, diarrhea, and decreased appetite are other side effects of this medication as well. Cinacalcet can cause hypocalcemia. The patients on this medication need to be closely followed for common symptoms associated with hypocalcemia include tingling, muscle twitching, cramps, changes in mood, or irritability. On the ECG, a prolonged QT interval may be present. Patients with a history of congenital long QT syndrome, family history of long QT syndrome, and other conditions that predispose patients to QT interval prolongation may be at increased risk.[11] Oversuppresion of PTH can cause adynamic bone disease.

Contraindications

Calcium level below 8.4 milligrams per deciliter is a contraindication to initiating this medication.[11]

Monitoring

Calcium levels need to be followed closely for any patient on this medication. Patients require assessment for signs and symptoms of hypocalcemia. Individuals on this medication need monitoring for side effects, including nausea and vomiting.[11] Cinacalcet may interact with other medications such as anticholinesterase inhibitors in dementia patients. Patients with hepatic impairment and hepatic impairment should have close monitoring.[3]

Toxicity

There is no “toxic” level of cinacalcet. Dose-limiting effects include nausea and vomiting, which would limit or preclude its use.[11] If hypocalcemia is present, the clinician should discontinue the medication, and hypocalcemia should have treated with intravenous calcium. Other electrolyte abnormalities, including magnesium and phosphorous, also need to be monitored.[11] To date, there is not much evidence to validate cinacalcet’s use or its toxicity in pregnant women.

Enhancing Healthcare Team Outcomes

With the rise in the burden of non-communicable diseases, i.e., cardiovascular and chronic kidney disease, healthcare providers must refine all their non-surgical options. Cinacalcet, a calcimimetic that counteracts the increase in PTH, is gaining center stage. When instituting a multi-modality approach for calciphylaxis, chronic kidney disease, and hyperparathyroidism, this medication is one of the ‘essentials’ in the medical armamentarium.

Cinacalcet therapy is best when provided through an interprofessional healthcare team, including clinicians, mid-level practitioners (NPs and PAs), specialists, nurses, and pharmacists, all working together and having access to all patient information so they can drive the best possible patient outcomes. [Level 5]

Nephrologists most commonly prescribe it for patients with secondary hyperparathyroidism on dialysis. Endocrinologists may prescribe it in patients with primary hyperparathyroidism in patients in whom surgical intervention is not an option or who would otherwise be too high risk for surgery. Patients need to be aware of side effects, including nausea and vomiting. They also should be educated about the symptoms of hypocalcemia. Calcium levels should be monitored closely in these patients. The interprofessional healthcare team should also engage the consult of a clinical pharmacist to optimize therapeutic results and minimize adverse events.

Review Questions

Access free multiple choice questions on this topic.
Comment on this article.

References

1.: Sekercioglu N, Busse JW, Sekercioglu MF, Agarwal A, Shaikh S, Lopes LC, Mustafa RA, Guyatt GH, Thabane L. Cinacalcet versus standard treatment for chronic kidney disease: a systematic review and meta-analysis. Ren Fail. 2016 Jul;38(6):857-74. [PubMed: 27137817]
2.: Sohn WY, Portale AA, Salusky IB, Zhang H, Yan LL, Ertik B, Shahinfar S, Lee E, Dehmel B, Warady BA. An open-label, single-dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cinacalcet in pediatric subjects aged 28 days to < 6 years with chronic kidney disease receiving dialysis. Pediatr Nephrol. 2019 Jan;34(1):145-154. [PMC free article: PMC6244811] [PubMed: 30141180]
3.: Junaid SZS, Patel JB. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Aug 12, 2022. Cinacalcet. [PubMed: 32491590]
4.: Cetani F, Saponaro F, Marcocci C. Non-surgical management of primary hyperparathyroidism. Best Pract Res Clin Endocrinol Metab. 2018 Dec;32(6):821-835. [PubMed: 30665549]
5.: Deen J, Schaider H. The use of cinacalcet for the treatment of calciphylaxis in patients with chronic kidney disease: A comprehensive review. Australas J Dermatol. 2019 Aug;60(3):e186-e194. [PubMed: 30666627]
6.: Takeuchi Y, Takahashi S, Miura D, Katagiri M, Nakashima N, Ohishi H, Shimazaki R, Tominaga Y. Cinacalcet hydrochloride relieves hypercalcemia in Japanese patients with parathyroid cancer and intractable primary hyperparathyroidism. J Bone Miner Metab. 2017 Nov;35(6):616-622. [PubMed: 27873072]
7.: Silverberg SJ, Rubin MR, Faiman C, Peacock M, Shoback DM, Smallridge RC, Schwanauer LE, Olson KA, Klassen P, Bilezikian JP. Cinacalcet hydrochloride reduces the serum calcium concentration in inoperable parathyroid carcinoma. J Clin Endocrinol Metab. 2007 Oct;92(10):3803-8. [PubMed: 17666472]
8.: Nagano N. Pharmacological and clinical properties of calcimimetics: calcium receptor activators that afford an innovative approach to controlling hyperparathyroidism. Pharmacol Ther. 2006 Mar;109(3):339-65. [PubMed: 16102839]
9.: Pi M, Chen L, Huang M, Luo Q, Quarles LD. Parathyroid-specific interaction of the calcium-sensing receptor and G alpha q. Kidney Int. 2008 Dec;74(12):1548-56. [PMC free article: PMC2760404] [PubMed: 18813283]
10.: Conigrave AD. The Calcium-Sensing Receptor and the Parathyroid: Past, Present, Future. Front Physiol. 2016;7:563. [PMC free article: PMC5156698] [PubMed: 28018229]
11.: Poon G. Cinacalcet hydrochloride (Sensipar). Proc (Bayl Univ Med Cent). 2005 Apr;18(2):181-4. [PMC free article: PMC1200722] [PubMed: 16200170]

: Disclosure: Syeda Zeenat Junaid declares no relevant financial relationships with ineligible companies.
: Disclosure: Jayesh Patel declares no relevant financial relationships with ineligible companies.

Cinacalcet Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

Uses

Cinacalcet is used to treat increased amounts of a certain hormone (parathyroid) in people with long-term kidney disease who are on dialysis. It is also used to treat increased amounts of calcium in people with an overactive parathyroid gland or in people with cancer of the parathyroid gland. Cinacalcet works by decreasing the amount of parathyroid hormone, calcium, and phosphorus in your body. Having the right amount of these substances in your body helps to prevent bone disease.

How to use Cinacalcet HCL

Take this medication by mouth with food or shortly after a meal, as directed by your doctor.

The manufacturer directs not to split, chew, or crush the tablet before taking it. However, many similar drugs (immediate-release tablets) can be split, chewed, or crushed. Follow your doctor’s directions on how to take this medication.

The dosage is based on your medical condition, response to treatment, and laboratory tests.

Take this medication regularly in order to get the most benefit from it. Remember to take it at the same time(s) each day.

Side Effects

Nausea, vomiting, or unusual tiredness may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.

Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Cinacalcet can cause low calcium blood levels. Your doctor will check your calcium blood levels while you are taking this medication. Tell your doctor right away if you have any of the following symptoms of low calcium levels: numb/tingling skin, severe muscle spasms, seizures, fast/irregular/pounding heartbeat.

Tell your doctor right away if you have any serious side effects, including: black/bloody stools, stomach/abdominal pain, vomit that contains blood or looks like coffee grounds.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US – Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Precautions

Before taking cinacalcet, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: low levels of calcium in the blood (hypocalcemia), seizures, stomach/intestinal problems (such as ulcers, gastritis, heartburn).

Very low levels of calcium can affect the heart rhythm (QT prolongation, ventricular arrhythmias). This risk may be increased if you have certain conditions or are taking drugs that can affect the heart rhythm. Before taking cinacalcet, tell your doctor of all the drugs you take and if you have heart rhythm problems or other heart problems (such as heart failure, low blood pressure).

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding.

Interactions

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.

A product that may interact with this drug is: thioridazine.

If your doctor tells you to switch from using this medication to etelcalcetide, this medication should be stopped at least 7 days before starting etelcalcetide. Using both medications together may increase the risk of side effects (especially low calcium levels).

Does Cinacalcet HCL interact with other drugs you are taking?

Enter your medication into the WebMD interaction checker

Overdose

If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe muscle spasms, seizures.

Do not share this medication with others.

Lab and/or medical tests (such as calcium, phosphorus, parathyroid hormone levels) should be done while you are taking this medication. Keep all medical and lab appointments. Consult your doctor for more details.

If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.