cinacalcet hydrochloride

Action

Directly lowers parathyroid hormone (PTH) levels by increasing sensitivity of calcium-sensing receptors to extracellular calcium

Availability

Tablets: 30 mg, 60 mg, 90 mg

Indications and dosages

➣ Secondary hyperparathyroidism in patients with chronic renal disease who are on dialysis

Adults: Dosage individualized; recommended starting dosage is 30 mg P.O. daily. Measure serum calcium and phosphorus levels within 1 week and intact parathyroid hormone (iPTH) 1 to 4 weeks after initiation or dosage adjustment; titrate dosage no more often than every 2 to 4 weeks through sequential doses of 60 mg, 90 mg, 120 mg, and 180 mg P.O. once daily to recommended target iPTH for chronic renal disease patients on dialysis of 150 to 300 pg/ml.

➣ Hypercalcemia in patients with parathyroid carcinoma

Adults: Recommended starting dosage is 30 mg P.O. twice daily, titrated every 2 to 4 weeks through sequential doses of 60 mg and 90 mg twice daily, and 90 mg three or four times daily as needed to normalize serum calcium level.

Dosage adjustment

• Decreased calcium or iPTH level

• Concurrent use or discontinuation of strong CYP3A4 inhibitors (such as erythromycin, itraconazole, or ketoconazole)

Contraindications

• Hypersensitivity to drug or its components

Precautions

Use cautiously in:

• decreased serum calcium level, moderate or severe hepatic impairment

• pregnant or breastfeeding patients

• children (safety and efficacy not established).

Administration

• Don't initiate therapy if serum calcium level is less than lower limit of normal range (8.4 mg/dl).

• Administer tablets whole with food or shortly after a meal.

• If iPTH level decreases below recommended target range (150 to 300 pg/ml), reduce dosage of cinacalcet and vitamin D sterols or discontinue therapy.

• During titration, monitor serum calcium level frequently; if level drops below normal, take appropriate measures to increase it, such as providing supplemental calcium, initiating or increasing dosage of calcium-based phosphate binder or vitamin D sterols, or withholding cinacalcet temporarily.

• Adjust dosage and closely monitor iPTH and calcium levels if patient is receiving or discontinuing a strong CYP3A4 inhibitor.

Adverse reactions

CNS: dizziness, asthenia

CV: hypertension

GI: nausea, vomiting, diarrhea, anorexia

Musculoskeletal: myalgia

Other: chest pain (noncardiac)

Interactions

Drug-drug. Amitriptyline: increased amitriptyline and nortriptyline (active metabolite) exposure

Drugs metabolized by CYP4502D6 (such as flecainide, thioridazine, most tricyclic antidepressants, vinblastine): increased blood levels of either drug

Ketoconazole and other strong CYP3A4 inhibitors: increased cinacalcet exposure

Drug-diagnostic tests. Calcium: decreased

Patient monitoring

• Closely monitor iPTH and serum calcium levels throughout therapy in patients with moderate to severe hepatic impairment and in those who start or discontinue therapy with strong CYP3A4 inhibitor.

• Monitor iPTH level carefully to ensure that it doesn't fall below 100 pg/ml because adynamic bone disease may develop.

• Measure serum calcium and phosphorus levels within 1 week and iPTH level 1 to 4 weeks after initiation or dosage adjustment. Once maintenance dosage is established, measure serum calcium and phosphorus levels approximately monthly and iPTH level every 1 to 3 months.

• Monitor serum calcium level closely in patient with history of seizure disorders.

Patient teaching

• Instruct patient to take tablets whole with food or shortly after a meal.

• As appropriate, review all other significant adverse reactions and interactions, especially those related to the drugs and tests mentioned above.