Cinacalcet, sold under the brand name Sensipar among others, is a medication used to treat

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 calciu ...

tertiary hyperparathyroidism 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 ...

and

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 Mana ...

. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. 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 hyperparathy ...

(i.e., it mimics the action of

calcium Calcium is a chemical element; it has 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 it ...

on tissues) by

allosteric In the fields of biochemistry and pharmacology an allosteric regulator (or allosteric modulator) is a substance that binds to a site on an enzyme or receptor distinct from the active site, resulting in a conformational change that alters the p ...

activation of the

calcium-sensing receptor 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, pancreatic islets and the br ...

that is expressed in various human organ tissues. The most common side effects include

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

and

vomiting Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...

. 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 most 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 Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range for total calcium 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 def ...

in people with parathyroid carcinoma. Cinacalcet can also be used to treat severe hypercalcemia in patients with primary hyperparathyroidism 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): hyperpa ...

. 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 Hypocalcemia is a medical condition characterized by low calcium levels in the blood serum. The normal range of blood calcium is typically between 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), while levels less than 2.1 ...

(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

paresthesia Paresthesia is a sensation of the skin that may feel like numbness (''hypoesthesia''), tingling, pricking, chilling, or burning. It can be temporary or Chronic condition, chronic and has many possible underlying causes. Paresthesia is usually p ...

myalgia Myalgia or muscle pain is a painful sensation evolving from muscle tissue. It is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another likely cause is viral infection, espec ...

s, muscle cramping, tetany, and

convulsion A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is often used as a synony ...

s. 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 upset stomach, 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 respo ...

(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 The lips are a horizontal pair of soft appendages attached to the jaws and are the most visible part of the mouth of many animals, including humans. Mammal lips are soft, movable and serve to facilitate the ingestion of food (e.g. sucklin ...

tongue The tongue is a Muscle, muscular organ (anatomy), organ in the mouth of a typical tetrapod. It manipulates food for chewing and swallowing as part of the digestive system, digestive process, and is the primary organ of taste. The tongue's upper s ...

fingers A finger is a prominent digit on the forelimbs of most tetrapod vertebrate animals, especially those with prehensile extremities (i.e. hands) such as humans and other primates. Most tetrapods have five digits (pentadactyly), Chambers 1998 p. 60 ...

, or

feet The foot (: feet) is an anatomical structure found in many vertebrates. It is the terminal portion of a limb which bears weight and allows locomotion. In many animals with feet, the foot is an organ at the terminal part of the leg made up of ...

* muscle aches or

cramps A cramp is a sudden, involuntary, painful skeletal muscle contraction or overshortening associated with electrical activity. While generally temporary and non-damaging, they can cause significant pain and a paralysis-like immobility of the affe ...

* sudden tightening of muscles in

hands A hand is a prehensile, multi-fingered appendage located at the end of the forearm or forelimb of primates such as humans, chimpanzees, monkeys, and lemurs. A few other vertebrates such as the koala (which has two opposable thumbs on each "han ...

, feet,

face The face is the front of the head that features the eyes, nose and mouth, and through which animals express many of their emotions. The face is crucial for human identity, and damage such as scarring or developmental deformities may affect th ...

, or

throat In vertebrate anatomy, the throat is the front part of the neck, internally positioned in front of the vertebrae. It contains the Human pharynx, pharynx and larynx. An important section of it is the epiglottis, separating the esophagus from the t ...

seizures A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

Interactions

Cinacalcet is a strong inhibitor of the liver enzyme

CYP2D6 Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra. CYP2 ...

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, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

and

CYP1A2 Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the ''CYP1A2'' gene. Function ...

. 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

(i.e. it mimics the action of calcium on tissues) by allosteric activation of the

that is expressed in various human organ tissues. The calcium-sensing receptors on the surface of the chief cell of the

parathyroid gland Parathyroid glands are small endocrine glands in the neck of humans and other tetrapods. Humans usually have four parathyroid glands, located on the back of the thyroid gland in variable locations. The parathyroid gland produces and secretes par ...

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

{{Authority control CYP2D6 inhibitors Nephrology procedures Systemic hormonal preparations Trifluoromethyl compounds 1-Naphthyl compounds Pharmacology