Cinacalcet, sold under the brand name Sensipar among others, is a medication used to treat tertiary hyperparathyroidism, parathyroid carcinoma, and primary hyperparathyroidism.
[ Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.]
The most common side effects include nausea (feeling sick) and vomiting.
Cinacalcet acts as a
calcimimetic 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 hyperparathyro ...
(i.e., it mimics the action of
calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...
on
tissues) by
allosteric
In biochemistry, allosteric regulation (or allosteric control) is the regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site.
The site to which the effector binds is termed the ''allosteric site ...
activation of the
calcium-sensing receptor that is expressed in various human organ tissues.
Cinacalcet was approved in the United States in March 2004,
[ ] and in the European Union in October 2004.
It was the first allosteric G protein-coupled receptor modulator to enter the pharmaceutical market.
In 2013, cinacalcet was the 76th top prescribed medicine in the United States.
Medical uses
In the United States, cinacalcet is indicated for the treatment of
secondary hyperparathyroidism
Secondary hyperparathyroidism is the medical condition of excessive secretion of parathyroid hormone (PTH) by the parathyroid glands in response to hypocalcemia (low blood calcium levels), with resultant hyperplasia of these glands. This disorde ...
in people with chronic kidney disease on dialysis and hypercalcemia in people with
parathyroid carcinoma
Parathyroid carcinoma is a rare cancer resulting in parathyroid adenoma to carcinoma progression.Hu MI, Vassilopoulou-Sellin R, Lustig R, Lamont JP"Thyroid and Parathyroid Cancers"in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (EdsCancer Managem ...
.
Cinacalcet can also be used to treat severe hypercalcemia in patients with
primary hyperparathyroidism
Primary hyperparathyroidism (or PHPT) is a medical condition where the parathyroid gland (or a benign tumor within it) produce excess amounts of parathyroid hormone (PTH). The symptoms of the condition relate to the resulting elevated serum calcium ...
who are unable to undergo
parathyroidectomy
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): hyperparathy ...
.
In the European Union cinacalcet is indicated for:
* the treatment of secondary hyperparathyroidism (HPT) in adults with end stage renal disease (ESRD) on maintenance dialysis therapy.
* the treatment of secondary hyperparathyroidism (HPT) in children aged three years and older with end stage renal disease (ESRD) on maintenance dialysis therapy in whom secondary HPT is not adequately controlled with standard of care therapy.
* part of a therapeutic regimen including phosphate binders and/or vitamin D sterols, as appropriate.
* the treatment of parathyroid carcinoma and primary hyperparathyroidism in adults.
* the reduction of hypercalcaemia in adults with:
** parathyroid carcinoma;
** primary HPT for whom parathyroidectomy would be indicated on the basis of serum calcium levels (as defined by relevant treatment guidelines), but in whom parathyroidectomy is not clinically appropriate or is contraindicated.
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.
Studies have not been done in lactating women; therefore it is not known whether cinacalcet is excreted into human milk.
Contraindications
Hypocalcemia (decreased calcium levels) is a contraindication of cinacalcet. Those who have serum calcium levels less than 7.5 mg/dL should not be started on cinacalcet. Hypocalcemia symptoms include parathesias, 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.
Cinacalcet is not approved for pediatric use in the United States.
[ ]
Adverse effects
Common side effects of cinacalcet include stomach upset, vomiting, diarrhea, dizziness, nausea, weakness, and chest pain.
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
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) in February 2013, following the death of a 14-year-old participant.
Overdose
Serious side effects, including overdose symptoms, of cinacalcet include:
* burning
* tingling
* unusual feelings of the lips, tongue, fingers, or feet
* muscle aches or cramps
* sudden tightening of muscles in hands, feet, face, or throat
* seizures
Interactions
Cinacalcet is a strong inhibitor of the liver enzyme
CYP2D6 and is partially metabolized by
CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...
and
CYP1A2. Dose adjustments may be necessary if people are treated with CYP3A4 and CYP1A2 inhibitors and medications that are metabolized by CYP2D6.
Pharmacology
Mechanism of action
Cinacalcet is a drug that acts as a
calcimimetic 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 hyperparathyro ...
(i.e. it mimics the action of calcium on tissues) by
allosteric activation
In biochemistry, allosteric regulation (or allosteric control) is the regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site.
The site to which the effector binds is termed the ''allosteric sit ...
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.
Cinacalcet increases the sensitivity of calcium receptors on parathyroid cells to reduce parathyroid hormone (PTH) levels and thus decrease serum calcium levels.
References
External links
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CYP2D6 inhibitors
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Trifluoromethyl compounds
1-Naphthyl compounds