cinacalcet

Absorption: Well absorbed following oral administration; absorption is enhanced by food and further enhanced by a high-fat meal.

Distribution: Extensively distributed to tissues.

Protein Binding: 93–97%.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A4, CYP2D6, and CYP1A2 isoenzymes; 80% excreted in urine as metabolites, 15% in feces.

Half-Life: 30–40 hr.

Time/Action Profile ⬆ ⬇

(effect on PTH levels)

ROUTE	ONSET	PEAK	DURATION
PO	rapid	2–6 hr	6–12 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Hypocalcemia.

Use Cautiously in:

History of seizure disorder (↑ risk of seizures with hypocalcemia);
Chronic kidney disease patients who are not being dialyzed (↑ risk of hypocalcemia);
Intact parathyroid hormone (iPTH) level <150 pg/mL (dose ↓ or discontinuation may be warranted);
Moderate or severe hepatic impairment;
Congenital long QT syndrome, QT interval prolongation, family history of long QT syndrome or sudden cardiac death, or concurrent use of QT-interval-prolonging medications;
OB: Safety not established in pregnancy;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: ARRHYTHMIA, HF exacerbation, hypotension, QT interval prolongation, TORSADES DE POINTES

F and E: HYPOCALCEMIA

GI: nausea, vomiting

Metab: adynamic bone disease

Neuro: SEIZURES

Interactions ⬆ ⬇

Drug-drug:

Concurrent use of QT interval prolonging medications may ↑ risk of QT interval prolongation and/or torsade de pointes, especially in patients with hypocalcemia.
May ↑ levels and risk of toxicity of CYP2D6 substrates, including flecainide, vinblastine, thioridazine, metoprolol, carvedilol, and most tricyclic antidepressants; dose adjustments may be necessary.
Strong CYP3A4 inhibitors, including ketoconazole, itraconazole, and erythromycin, may ↑ levels and risk of toxicity; monitoring and dose adjustment may be necessary.

Route/Dosage ⬆ ⬇

Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease on Dialysis

PO (Adults ): 30 mg once daily; may ↑ dose every 2–4 wk (dose range 30–180 mg once daily) based on iPTH levels. Switching from etecalcetide: Discontinue etecalcetide for ≥4 wk and ensure corrected serum calcium is at or above lower limit of normal prior to starting cinacalcet.

Parathyroid Carcinoma or Primary Hyperparathyroidism

PO (Adults ): 30 mg twice daily; may ↑ every 2–4 wk up to 90 mg 3–4 times daily based on serum calcium levels.

Availability ⬆ ⬇

(Generic available)

Tablets: 30 mg; 60 mg; 90 mg

Assessment ⬆ ⬇

Monitor for signs and symptoms of hypocalcemia (paresthesias, myalgias, cramping, tetany, convulsions) during therapy. If calcium levels decrease to below normal, serum calcium may be increased by adjusting dose (see Lab Test Considerations) and providing supplemental serum calcium, initiating or increasing dose of calcium-based phosphate binder or vitamin D.
Monitor ECG for prolonged QT interval periodically during therapy.

Lab Test Considerations:

Monitor serum calcium and phosphorus levels within 1 wk after initiation of therapy or dose adjustment and monthly for patients with hyperparathyroidism or every 2 mo for patients with parathyroid carcinoma once maintenance dose has been established, especially in patients with a history of seizure disorder. Therapy should not be initiated in patients with serum calcium less than the lower limit of normal (8.4 mg/dL).
- If serum calcium ↓ below 8.4 mg/dL but remains above 7.5 mg/dL, or if symptoms of hypocalcemia occur, use calcium-containing phosphate binders and/or vitamin D sterols to ↑ serum calcium. If serum calcium ↓ below 7.5 mg/dL, or if symptoms of hypocalcemia persist and the dose of vitamin D cannot be ↑, withhold administration of cinacalcet until serum calcium levels reach 8.0 mg/dL and/or symptoms of hypocalcemia resolve. Reinitiate therapy using next lowest dose of cinacalcet.
- Monitor serum iPTH levels 1 to 4 wk after initiation of therapy or dose adjustment, and every 1 to 3 mo after maintenance dose has been established. If iPTH levels ↓ below 150–300 pg/mL, reduce dose or discontinue cinacalcet. Assess iPTH levels no earlier than 12 hr after dose.
- Monitor liver function tests in patients with moderate to severe hepatic impairment during therapy.

Implementation ⬆ ⬇

Cinacalcet may be used alone or in combination with vitamin D and/or phosphate binders.
PO: Administer with food or shortly after a meal. Take tablets whole; DNC: do not crush, break, or chew.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take cinacalcet as directed.
Advise patient to report signs and symptoms of hypocalcemia, GI bleeding (black tarry stools, abdominal pain), nausea, and vomiting to health care professional promptly.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breastfeeding.
Emphasize the importance of follow-up lab tests to monitor safely and efficacy.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇