Cinacalcet

Cinacalcet is the first drug in a new class of compounds called calcimimetics, which activate calcium receptors in the parathyroid glands, thereby reducing the secretion of parathyroid hormone (PTH).

Chinese name: Cinacalcet

English name: Cinacalcet

Indications

(1) This product is used to treat secondary hyperparathyroidism in patients with chronic kidney disease (CKD) undergoing dialysis;

(2) It is used to treat hypercalcemia in patients with parathyroid cancer;

(3) Mainly used in patients with severe hypercalcemia. HPT Those who cannot undergo parathyroidectomy.

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 daily, 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 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.

Pharmacological effects

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.

Drug Interactions

1. This product is a strong CYP2D6 inhibitor and can increase the AUC of amitriptyline by 20%. 2. This product is mainly metabolized by CYP3A4. When combined with the CYP3A4 inhibitor ketoconazole, the AUC and Cmax of this product will increase by 2.3 times and 2.2 times respectively. When combined with the potent CYP3A4 inhibitors ketoconazole, itraconazole, and erythromycin ethylsuccinate, patients' PTH and serum calcium concentrations should be closely monitored.

Pharmacokinetics

The blood concentration of this product reaches the peak value (Cmax) 2 to 6 hours after oral administration. When taken with high-fat food, the Cmax and area under the drug-time curve (AUC) of this product increase by 82% and 68% respectively; when taken with low-fat food, the peak concentration Cmax and AUC of this product increase by 65% ​​and 50% respectively. After absorption, the blood concentration of this product is eliminated in a biphasic manner, with an elimination half-life of 30 to 40 hours. After 7 days of continuous administration, the plasma concentration reached a steady state, and Cmax and AUC increased proportionally with the increase in dosage. The apparent distribution volume is 1000L, indicating that this product is widely distributed. This product is 93% to 97% bound to plasma proteins. This product is metabolized by a variety of enzymes, mainly CYP3A4, CYP2D6, and CYPlA2. It is mainly excreted through the kidneys, accounting for 80% of the administered dose, and about 15% is excreted through the feces. In patients with moderate and severe hepatic impairment, the AUC increased by 2.4 times and 4.2 times, respectively, and the half-life was prolonged by 33% and 70%.

Adverse reactions

The most common adverse reactions of this product 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 by paresthesia, myalgia, cramps, tetany and convulsions.

Notes

1. This product has a reproductive toxicity classification of C and can be used in pregnant women only when the benefits to the mother outweigh the risks to the fetus.

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

3． 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.

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

5． Safety in children has not been evaluated.

6. Overdose of this product can cause hypocalcemia, and 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.

7. Store at 15~30℃.

Disabled, use with caution

1. It is prohibited for those who are allergic to this product and its ingredients.

2. 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.

Storage

Stored at 15～30℃.