Cinacalcet:Brand name, Uses, Pharmacokinetics and Precautions

Cinacalcet is a white to off-white, crystalline solid that is soluble in methanol or 95% ethanol and slightly soluble in water. Cinacalcet is a calcimimetic agent that increases the sensitivity of the calcium-sensing receptor to activation by extracellular calcium. It has one chiral center having an R-absolute configuration.

Brand name

Sensipar

Uses

Cinacalcet is a calcium-sensing receptor agonist indicated for:

• Secondary Hyperparathyroidism (HPT) in patients with chronic kidney disease (CKD) on dialysis.

• Hypercalcemia in patients with Parathyroid Carcinoma (PC).

• Severe hypercalcemia in patients with primary HPT who are unable to undergo parathyroidectomy.

Side effects

Allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue;

Depressed mood:

signs and symptoms of a dangerous change in heartbeat or heart rhythm like chest pain; dizziness; fast or irregular heartbeat; palpitations; feeling faint or lightheaded, falls; breathing problems signs and symptoms of bleeding such as bloody or black, tarry stools; spitting up blood or brown material that looks like coffee grounds signs and symptoms of low blood pressure like dizziness; feeling faint or lightheaded, falls; unusually weak or tired signs and symptoms of low calcium like fast heartbeat, muscle cramps or muscle pain; pain, tingling, numbness in the hands or feet; seizures;

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):

bone pain

diarrhea

joint pain

loss of appetite

nausea, vomiting

Pharmacokinetics

Absorption and Distribution: After oral administration of cinacalcet, maximum plasma concentration (Cmax) is achieved in approximately 2 to 6 hours. Cmax and AUC(0-inf) of cinacalcet were increased 65% and 50%, respectively, when cinacalcet was administered with a low-fat meal compared to fasting.

After absorption, cinacalcet concentrations decline in a biphasic fashion with a terminal half-life of 30 to 40 hours. Steady-state drug levels are achieved within 7 days.

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 rapidly and extensively 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 to form 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 parent drug concentrations.

Precautions

Hypocalcemia and/or seizures: May occur due to significant reductions in serum calcium.

•Isolated, idiosyncratic occurrences of hypotension, worsening heart failure, and/or arrhythmia: Have been reported in patients with impaired cardiac function during Sensipar treatment, which may be mediated by reductions in serum calcium.

•Adynamic bone disease: May develop if iPTH levels are suppressed.