Cinacalcet

Introduction to Cinacalcet Hydrochloride

Common name: Cinacalcet

Trade name: Mimpara

All names: Cinacalcet hydrochloride, Cinacalcet, Mimpara, Regpara, CTH-30

Indications:

This product is used to treat secondary hyperparathyroidism in patients with chronic kidney disease (CKD) undergoing dialysis, and is also used to treat hypercalcemia in patients with parathyroid cancer.

Usage and dosage:

For oral administration, the tablet should be swallowed whole and should not be broken. It should be taken with food or within a short time after a meal. The dosage should be individualized.

For secondary hyperparathyroidism in CKD patients on dialysis: the recommended starting dose is 30 mg once a day, with blood calcium and phosphorus levels measured within 1 week, and PTH levels measured within 1 to 4 weeks. The daily dose adjustment time to 60 mg, 90 mg, 120 mg, and 180 mg shall not be less than 2 to 4 weeks. The patient's PTH concentration should be controlled between 150 and 300pg/ml.

For the treatment of hypercalcemia in patients with parathyroid cancer: the recommended starting dose is 30 mg twice daily. The dose is adjusted once every 2 to 4 weeks. According to the blood calcium concentration, the dose can be adjusted to 60 mg each time, 2 times a day; 90 mg each time, 2 times a day; 90 mg each time, 3 to 4 times a day.

Adverse reactions:

The most common adverse reactions are nausea and vomiting

Other adverse reactions include: diarrhea, myalgia, dizziness, hypertension, weakness, loss of appetite, and chest pain.

Overdose of this product can cause hypocalcemia, manifested as paresthesia, myalgia, cramps, tetany and convulsions.

Contraindications:

Contraindicated for those allergic to this product and its ingredients.

It is not known whether this product is excreted in human milk. Due to the serious adverse reactions of this product, it is not recommended for lactating women. If used, breastfeeding should be stopped during the medication.

Notes:

The reproductive toxicity classification of this product is C. It can only be used in pregnant women when the benefit to the mother is higher than the risk to the fetus.

This product can cause epileptic seizures. Plasma calcium concentration should be closely monitored during medication, especially in patients with a history of epilepsy.

This product can cause hypocalcemia. Blood calcium levels should be monitored weekly at the beginning of treatment and once a month after the treatment dose is determined.

Patients with moderate to severe hepatic impairment should be monitored during treatment.

The safety of the drug in children has not been evaluated.

Excessive use of this product can cause hypocalcemia. Clinical symptoms of hypocalcemia should be closely observed and symptomatic treatment should be taken. Due to the high plasma protein binding rate of this product, dialysis treatment is ineffective.

Storage:

Stored at 15~30℃

Mechanism of action:

Secondary hyperparathyroidism in patients with chronic kidney disease (CKD) is a progressive disease caused by elevated levels of parathyroid hormone (PTH) causing calcium and phosphorus metabolism disorders. Elevated PTH stimulates osteoclast activity and causes bone resorption. The purpose of treatment for secondary hyperparathyroidism is to reduce PTH, blood calcium, and blood phosphorus, and prevent bone disease and systemic effects caused by imbalanced mineral metabolism. Calcium-sensitive receptors located on the main cells of the parathyroid gland are the main regulators of PTH secretion. This product can increase the sensitivity of calcium-sensitive receptors to extracellular calcium and reduce PTH levels, thereby reducing plasma calcium concentration.

Safety and efficacy:

Traditional treatments for secondary hyperparathyroidism (SHPT) include the use of phosphate binders and supplementation of active vitamin D, but the treatment compliance rate is low. Cinacalc, the first calcimimetic agent marketed in the United States, Canada and Europe et, can significantly enhance the sensitivity of calcium sensing receptors of parathyroid chief cells to extracellular calcium ions, reduce parathyroid hormone, blood calcium, phosphorus concentration and calcium-phosphorus product. Multiple large-scale randomized double-blind placebo-controlled studies have confirmed that this product is effective in SHPT patients undergoing dialysis due to chronic kidney disease, and has good safety and tolerability.

Researchers at the Department of Endocrinology at IRCCS Granda Hospital conducted a randomized, crossover, double-blind study to evaluate the efficacy of Cinacalcet in patients with MEN1 and sporadic PHPT (sPHPT). Differences in patient outcomes and the impact of the Arg990Gly calcium-sensing receptor polymorphism on treatment response. Cinacalcet was found to normalize serum calcium, increase phosphate, and reduce PTH levels. There was no significant difference in the dose of Cinacalcet required to normalize serum calcium in patients with MEN1 and sPHPT (45±21 vs 54±25mg/ sky). Only minor adverse effects were observed in both study groups and did not require discontinuation of treatment. No association between the Arg990Gly CASR polymorphism and the body's response to cinacalcet was found.