Cinacalcet

Last updated

Cinacalcet
Cinacalcet Structural Formulae.png
Cinacalcet ball-and-stick.png
Clinical data
Trade names Sensipar, Mimpara
AHFS/Drugs.com Monograph
MedlinePlus a605004
License data
Pregnancy
category
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only) [2]
  • UK: POM (Prescription only) [3]
  • US: ℞-only [4]
  • EU:Rx-only [5]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 20 to 25%
increases if taken with food
Protein binding 93 to 97%
Metabolism Hepatic (CYP3A4-, CYP2D6- and CYP1A2-mediated)
Elimination half-life 30 to 40 hours
Excretion Renal (80%) and fecal (15%)
Identifiers
  • (R)-N-[1-(1-naphthyl)ethyl]-3-
    [3-(trifluoromethyl)phenyl]propan-1-amine
CAS Number
PubChem CID
PubChemSID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.208.116 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C22H22F3N
Molar mass 357.420 g·mol−1
3D model (JSmol)
  • CC(C1=CC=CC2=CC=CC=C21)NCCCC3=CC(=CC=C3)C(F)(F)F
  • InChI=1S/C22H22F3N/c1-16(20-13-5-10-18-9-2-3-12-21(18)20)26-14-6-8-17-7-4-11-19(15-17)22(23,24)25/h2-5,7,9-13,15-16,26H,6,8,14H2,1H3/t16-/m1/s1 Yes check.svgY
  • Key:VDHAWDNDOKGFTD-MRXNPFEDSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Cinacalcet, sold under the brand name Sensipar among others, is a medication used to treat primary hyperparathyroidism, tertiary hyperparathyroidism and parathyroid carcinoma. [4] [6] [5] Cinacalcet acts as a calcimimetic (i.e., it mimics the action of calcium on tissues) by allosteric activation of the calcium-sensing receptor that is expressed in various human organ tissues.

Contents

The most common side effects include nausea and vomiting. [5]

Cinacalcet was approved in the United States in March 2004, [4] [7] [8] and in the European Union in October 2004. [5] [3] It was the first allosteric G protein-coupled receptor modulator to enter the pharmaceutical market. [9] In 2013, cinacalcet was the 76th most prescribed medicine in the United States. [10] [11]

Medical uses

In the United States, cinacalcet is indicated for the treatment of secondary hyperparathyroidism in people with chronic kidney disease on dialysis and hypercalcemia in people with parathyroid carcinoma. [4] [12] Cinacalcet can also be used to treat severe hypercalcemia in patients with primary hyperparathyroidism who are unable to undergo parathyroidectomy. [4] [13]

In the European Union cinacalcet is indicated for:

Pregnancy and lactation

Cinacalcet has pregnancy category C in the US, meaning that adequate and well-controlled studies involving cinacalcet in pregnant women have not been done. [4] [1]

Studies have not been done in lactating women; therefore, it is not known whether cinacalcet is excreted into human milk. [4] [1]

Contraindications

Hypocalcemia (decreased calcium levels) is a contraindication to the use of cinacalcet. Those who have serum calcium levels less than 7.5 mg/dL should not be started on cinacalcet. Hypocalcemia symptoms include paresthesias, myalgias, muscle cramping, tetany, and convulsions. Cinacalcet should not be administered until serum calcium levels are above 8.0 mg/dL and/or hypocalcemia symptoms are resolved. [4] Cinacalcet is not approved for pediatric use in the United States. [6] [4] [5]

Adverse effects

Common side effects of cinacalcet include upset stomach, vomiting, diarrhea, dizziness, nausea, weakness, and chest pain. [13]

Clinical trials conducted in the United States by Amgen to determine whether the drug is safe in children were halted by the U.S. Food and Drug Administration (FDA) in February 2013, following the death of a 14-year-old participant. [6] [14]

Overdose

Serious side effects, including overdose symptoms, of cinacalcet include: [13]

Interactions

Cinacalcet is a strong inhibitor of the liver enzyme CYP2D6 and is partially metabolized by CYP3A4 and CYP1A2. Dose adjustments may be necessary if people are treated with CYP3A4 and CYP1A2 inhibitors and medications that are metabolized by CYP2D6. [4] [3]

Pharmacology

Mechanism of action

Cinacalcet is a drug that acts as a calcimimetic [4] [5] (i.e. it mimics the action of calcium on tissues) by allosteric activation of the calcium-sensing receptor that is expressed in various human organ tissues. The calcium-sensing receptors on the surface of the chief cell of the parathyroid gland is the principal negative regulator of parathyroid hormone secretion. [15] Cinacalcet increases the sensitivity of calcium receptors on parathyroid cells to reduce parathyroid hormone (PTH) levels and thus decrease serum calcium levels. [12]

Related Research Articles

<span class="mw-page-title-main">Parathyroid hormone</span> Mammalian protein found in humans

Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine.

Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcemia. Those with a mild increase that has developed slowly typically have no symptoms. In those with greater levels or rapid onset, symptoms may include abdominal pain, bone pain, confusion, depression, weakness, kidney stones or an abnormal heart rhythm including cardiac arrest.

Disorders of calcium metabolism occur when the body has too little or too much calcium. The serum level of calcium is closely regulated within a fairly limited range in the human body. In a healthy physiology, extracellular calcium levels are maintained within a tight range through the actions of parathyroid hormone, vitamin D and the calcium sensing receptor. Disorders in calcium metabolism can lead to hypocalcemia, decreased plasma levels of calcium or hypercalcemia, elevated plasma calcium levels.

<span class="mw-page-title-main">Hyperparathyroidism</span> Increase in parathyroid hormone levels in the blood

Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands or as response to external stimuli. Symptoms of hyperparathyroidism are caused by inappropriately normal or elevated blood calcium excreted from the bones and flowing into the blood stream in response to increased production of parathyroid hormone. In healthy people, when blood calcium levels are high, parathyroid hormone levels should be low. With long-standing hyperparathyroidism, the most common symptom is kidney stones. Other symptoms may include bone pain, weakness, depression, confusion, and increased urination. Both primary and secondary may result in osteoporosis.

<span class="mw-page-title-main">Parathyroidectomy</span> Surgical removal of one or more of the parathyroid glands

Parathyroidectomy is the surgical removal of one or more of the (usually) four parathyroid glands. This procedure is used to remove an adenoma or hyperplasia of these glands when they are producing excessive parathyroid hormone (PTH): hyperparathyroidism. The glands are usually four in number and located adjacent to the posterior surface of the thyroid gland, but their exact location is variable. When an elevated PTH level is found, a sestamibi scan or an ultrasound may be performed in order to confirm the presence and location of abnormal parathyroid tissue.

Renal osteodystrophy is currently defined as an alteration of bone morphology in patients with chronic kidney disease (CKD). It is one measure of the skeletal component of the systemic disorder of chronic kidney disease-mineral and bone disorder (CKD-MBD). The term "renal osteodystrophy" was coined in 1943, 60 years after an association was identified between bone disease and kidney failure.

<span class="mw-page-title-main">Primary hyperparathyroidism</span> Medical condition

Primary hyperparathyroidism is a medical condition where the parathyroid gland produce excess amounts of parathyroid hormone (PTH). The symptoms of the condition relate to the resulting elevated serum calcium (hypercalcemia), which can cause digestive symptoms, kidney stones, psychiatric abnormalities, and bone disease.

<span class="mw-page-title-main">Osteitis fibrosa cystica</span> Medical condition

Osteitis fibrosa cystica is a skeletal disorder resulting in a loss of bone mass, a weakening of the bones as their calcified supporting structures are replaced with fibrous tissue, and the formation of cyst-like brown tumors in and around the bone. Osteitis fibrosis cystica (OFC), also known as osteitis fibrosa, osteodystrophia fibrosa, and von Recklinghausen's disease of bone, is caused by hyperparathyroidism, which is a surplus of parathyroid hormone from over-active parathyroid glands. This surplus stimulates the activity of osteoclasts, cells that break down bone, in a process known as osteoclastic bone resorption. The hyperparathyroidism can be triggered by a parathyroid adenoma, hereditary factors, parathyroid carcinoma, or renal osteodystrophy. Osteoclastic bone resorption releases minerals, including calcium, from the bone into the bloodstream, causing both elevated blood calcium levels, and the structural changes which weaken the bone. The symptoms of the disease are the consequences of both the general softening of the bones and the excess calcium in the blood, and include bone fractures, kidney stones, nausea, moth-eaten appearance in the bones, appetite loss, and weight loss.

<span class="mw-page-title-main">Secondary hyperparathyroidism</span> Medical condition

Secondary hyperparathyroidism is the medical condition of excessive secretion of parathyroid hormone (PTH) by the parathyroid glands in response to hypocalcemia, with resultant hyperplasia of these glands. This disorder is primarily seen in patients with chronic kidney failure. It is sometimes abbreviated "SHPT" in medical literature.

<span class="mw-page-title-main">Tertiary hyperparathyroidism</span> Medical condition

Tertiary hyperparathyroidism is a condition involving the overproduction of the hormone, parathyroid hormone, produced by the parathyroid glands. The parathyroid glands are involved in monitoring and regulating blood calcium levels and respond by either producing or ceasing to produce parathyroid hormone.

<span class="mw-page-title-main">Milk-alkali syndrome</span> Medical condition

Milk-alkali syndrome (MAS), also referred to as calcium-alkali syndrome, is the third most common cause of hypercalcemia. Milk-alkali syndrome is characterized by elevated blood calcium levels, metabolic alkalosis, and acute kidney injury.

<span class="mw-page-title-main">Calcium-sensing receptor</span> Mammalian protein found in humans

The calcium-sensing receptor (CaSR) is a Class C G-protein coupled receptor which senses extracellular levels of calcium ions. It is primarily expressed in the parathyroid gland, the renal tubules of the kidney and the brain. In the parathyroid gland, it controls calcium homeostasis by regulating the release of parathyroid hormone (PTH). In the kidney it has an inhibitory effect on the reabsorption of calcium, potassium, sodium, and water depending on which segment of the tubule is being activated.

<span class="mw-page-title-main">Parathyroid adenoma</span> Medical condition

A parathyroid adenoma is a benign tumor of the parathyroid gland. It generally causes hyperparathyroidism; there are very few reports of parathyroid adenomas that were not associated with hyperparathyroidism.

<span class="mw-page-title-main">Parathyroid carcinoma</span> Medical condition

Parathyroid carcinoma is a rare cancer resulting in parathyroid adenoma to carcinoma progression. It forms in tissues of one or more of the parathyroid glands.

<span class="mw-page-title-main">Parathyroid disease</span> Medical condition

Many conditions are associated with disorders of the function of the parathyroid gland. Some disorders may be purely anatomical resulting in an enlarged gland which will raise concern. Such benign disorders, such as parathyroid cyst, are not discussed here. Parathyroid diseases can be divided into those causing hyperparathyroidism, and those causing hypoparathyroidism.

Familial hypocalciuric hypercalcemia (FHH) is an inherited condition that can cause hypercalcemia, a serum calcium level typically above 10.2 mg/dL; although uncommon. It is also known as familial benign hypocalciuric hypercalcemia (FBHH) where there is usually a family history of hypercalcemia which is mild, a urine calcium to creatinine ratio <0.01, and urine calcium <200 mg/day.

A calcimimetic is a pharmaceutical drug that mimics the action of calcium on tissues, by allosteric activation of the calcium-sensing receptor that is expressed in various human organ tissues. Calcimimetics are used to treat secondary hyperparathyroidism (SHPT).

Recombinant human parathyroid hormone, sold under the brand name Preotact among others, is an artificially manufactured form of the parathyroid hormone used to treat hypoparathyroidism. Recombinant human parathyroid hormone is used in the treatment of osteoporosis in postmenopausal women at high risk of osteoporotic fractures. A significant reduction in the incidence of vertebral fractures has been demonstrated. It is used in combination with calcium and vitamin D supplements.

<span class="mw-page-title-main">Etelcalcetide</span> Chemical compound

Etelcalcetide, sold under the brand name Parsabiv, is a calcimimetic medication for the treatment of secondary hyperparathyroidism in people undergoing hemodialysis. It is administered intravenously at the end of each dialysis session. Etelcalcetide functions by binding to and activating the calcium-sensing receptor in the parathyroid gland. Parsabiv is currently owned by Amgen and Ono Pharmaceuticals in Japan.

<span class="mw-page-title-main">Upacicalcet</span> Chemical compound

Upacicalcet is a drug used to treat secondary hyperparathyroidism (SHPT) - a disease of the parathyroid gland - in dialysis patients. It was approved as Upasita in Japan in June 2021. The drug is given intravenously. The active ingredient is used in the form of its sodium salt.

References

  1. 1 2 3 "Cinacalcet (Sensipar) Use During Pregnancy". Drugs.com. 19 July 2019. Retrieved 24 December 2019.
  2. ↑ "Sensipar Tablets". NPS MedicineWise. 1 May 2018. Archived from the original on 7 December 2019. Retrieved 7 December 2019.
  3. 1 2 3 "Mimpara 30 mg Film-coated Tablets - Summary of Product Characteristics (SmPC)". electronic medicines compendium (emc). 8 July 2019. Archived from the original on 7 December 2019. Retrieved 7 December 2019.
  4. 1 2 3 4 5 6 7 8 9 10 11 "Sensipar- cinacalcet hydrochloride tablet, coated". DailyMed . 5 December 2019. Retrieved 24 December 2019.
  5. 1 2 3 4 5 6 7 8 9 10 11 12 "Mimpara EPAR". European Medicines Agency (EMA). 22 August 2019. Retrieved 23 December 2019. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  6. 1 2 3 "FDA Drug Safety Communication: Pediatric clinical studies of Sensipar (cinacalcet hydrochloride) suspended after report of death". U.S. Food and Drug Administration (FDA). 15 January 2016. Archived from the original on 24 December 2019. Retrieved 23 December 2019.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  7. ↑ "Drug Approval Package: Sensipar (Cinacalcet HCI) NDA #021688". U.S. Food and Drug Administration (FDA). 7 December 2019. Archived from the original on 7 December 2019. Retrieved 7 December 2019.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  8. ↑ "Sensipar". U.S. Food and Drug Administration (FDA). Archived from the original on 7 December 2019. Retrieved 7 December 2019.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  9. ↑ Bräuner-Osborne H, Wellendorph P, Jensen AA (2007). "Structure, pharmacology and therapeutic prospects of family C G-protein coupled receptors". Current Drug Targets. 8 (1): 169–84. doi:10.2174/138945007779315614. PMID   17266540.
  10. ↑ "U.S. Pharmaceutical Statistics". Drugs.com. February 2014. Retrieved 13 July 2020.
  11. ↑ "Sales Statistics for Sensipar Prescriptions". Drugs.com. 2 September 2020. Retrieved 8 September 2020.
  12. 1 2 2014 Nurses Drug Handbook (13th ed.). Burlington, MA: Jones & Bartlett Learning. 2014. pp.  245–6. ISBN   978-1-284-03115-7.
  13. 1 2 3 "Cinacalcet". U.S. National Library of Medicine. Retrieved 29 October 2014.
  14. ↑ Edney A (26 February 2013). "Amgen Pediatric Trials of Sensipar Halted by FDA After Death". Bloomberg Businessweek . Archived from the original on 2 March 2013. Retrieved 26 February 2013.
  15. ↑ "Cinacalcet".
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.