Cinacalcet Hydrochloride

Pronunciation

Pronunciation: SIN-a-KAL-set HYE-droe-KLOR-ide
Class: Calcimimetic

Trade Names

Sensipar
- Tablets, oral 30 mg
- Tablets, oral 60 mg
- Tablets, oral 90 mg

Pharmacology

Lowers parathyroid hormone (PTH) levels by increasing sensitivity of the calcium-sensing receptor to extracellular calcium.

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Pharmacokinetics

Absorption

T max is approximately 2 to 6 h. Steady state is achieved within 7 days. The C max and AUC (0-inf) were increased 82% and 68%, respectively, when cinacalcet was administered with a high-fat meal compared with fasting. The C max and AUC (0-inf) of cinacalcet were increased 65% and 50%, respectively, when cinacalcet was administered with a low-fat meal compared with fasting.

Distribution

Vd is approximately 1,000 L. Protein binding is 93% to 97%.

Metabolism

Metabolized by CYP3A4, CYP2D6, and CYP1A2.

Elimination

Terminal half-life is 30 to 40 h. Approximately 80% of a dose is recovered in the urine and 15% in the feces.

Special Populations

Renal Function Impairment

Pharmacokinetics in patients with mild, moderate, or severe renal impairment and those on hemodialysis or peritoneal dialysis are comparable with healthy volunteers.

Hepatic Function Impairment

In patients with moderate or severe hepatic impairment, the AUCs were 2.4 and 4.2 times higher, respectively, than in healthy subjects; the half-life is increased from 49 h in healthy subjects to 65 h and 84 h in patients with moderate and severe hepatic impairment, respectively.

Elderly

Pharmacokinetics are similar in patients 65 y and older compared with patients younger than 65 y.

Children

The pharmacokinetics have not been studied in patients younger than 18 y.

Indications and Usage

Treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis; hypercalcemia in patients with parathyroid carcinoma; for the treatment of severe hypercalcemia in patients with primary hyperparathyroidism who are unable to undergo parathyroidectomy.

Contraindications

Hypocalcemia.

Dosage and Administration

Hypercalcemia in Parathyroid Carcinoma and Primary Hyperparathyroidism
Adults

PO Start with 30 mg twice daily. Titrate every 2 to 4 wk through sequential doses of 30, 60, and 90 mg twice daily, and 90 mg 3 or 4 times daily as needed to normalize serum calcium levels.

Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease on Dialysis
Adults

PO Start with 30 mg daily. Titrate dose every 2 to 4 wk through sequential doses of 30, 60, 90, 120, and 180 mg daily based on target intact PTH levels of 150 to 300 pg/mL.

General Advice

  • Can be used alone or in combination with vitamin D and/or phosphate binders.
  • Administer with food or shortly after a meal. Swallow tablets whole and do not crush, chew, or divide.
  • Serum intact PTH levels should be assessed no earlier than 12 h after dosing.

Storage/Stability

Store between 59° and 86°F.

Drug Interactions

Drugs metabolized by CYP2D6 (eg, carvedilol, flecainide, metoprolol, thioridazine, most tricyclic antidepressants [eg, amitriptyline, desipramine])

Plasma concentrations of these agents may be elevated, increasing the pharmacologic effects and adverse reactions. Dosage adjustments may be needed, especially in agents with a narrow therapeutic index.

Strong inhibitors of CYP3A4 (eg, erythromycin, itraconazole, ketoconazole)

Cinacalcet concentrations may be elevated, increasing the pharmacologic effects and adverse reactions. Closely monitor patients and adjust the cinacalcet dose as needed.

Adverse Reactions

Cardiovascular

Hypertension (7%); arrhythmia, idiosyncratic hypotension, worsening heart failure (postmarketing).

CNS

Paresthesia (29%); fatigue, headache (21%); depression (18%); asthenia (17%); dizziness (10%).

GI

Nausea (66%); vomiting (52%); diarrhea (21%); constipation (18%).

Hypersensitivity

Hypersensitivity reactions, including angioedmea and urticaria (postmarketing).

Metabolic-Nutritional

Dehydration (24%); anorexia, hypercalcemia (21%).

Musculoskeletal

Fracture (21%); arthralgia (17%); myalgia (15%); limb pain (12%).

Miscellaneous

Anemia (17%); upper respiratory infection (12%); noncardiac chest pain (6%); access infection (5%); rash (postmarketing).

Precautions

Monitor

Carefully monitor patient for signs and symptoms of hypocalcemia (eg, convulsions, cramping, myalgia, paresthesias, tetany). Measure serum calcium and serum phosphorus within 1 wk and measure intact PTH 1 to 4 wk after initiating or adjusting the dose of cinacalcet. Once a maintenance dose is established, measure serum calcium and serum phosphorus monthly, and intact PTH every 1 to 3 mo; in parathyroid carcinoma patients, once the maintenance dose level has been established, measure serum calcium every 2 mo. Closely monitor intact PTH, serum phosphorus, and serum calcium concentrations throughout treatment in patients with moderate or severe hepatic impairment.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Hepatic Function

Use with caution in patients with moderate to severe hepatic impairment.

Adynamic bone disease

May occur if intact PTH levels are suppressed below 100 pg/mL. Ensure that the dose of cinacalcet and/or vitamin D is reduced if intact PTH levels decrease to less than 150 pg/mL.

Cardiovascular effects

During postmarketing experience, idiosyncratic cases of arrhythmia, hypotension, and/or worsening of heart failure have been reported in patients with impaired cardiac function.

Hypocalcemia

May occur; closely monitor. Do not initiate treatment if serum calcium is less than the lower limit of the normal range. If serum calcium falls 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 raise serum calcium. Ensure that cinacalcet is temporarily discontinued in patients whose serum calcium falls below 7.5 mg/dL or if symptoms of hypocalcemia persist and the dose of vitamin D cannot be increased. Therapy can be reinstituted using the next lowest dose when serum calcium level reaches 8 mg/dL and/or symptoms of hypocalcemia have resolved.

Seizures

Seizures may occur. Closely monitor serum calcium levels, particularly in patients with a history of seizures.

Overdosage

Symptoms

Hypocalcemia.

Patient Information

  • Advise patient to take prescribed dose with food or shortly after a meal. Caution patient to swallow tablets whole and not to chew, divide, or crush.
  • Caution patient not to change or stop taking the dose unless advised by health care provider.
  • Instruct patient to continue taking other medications (eg, vitamin D and/or phosphate binders) as prescribed by health care provider for controlling calcium levels.
  • Instruct patient to immediately inform health care provider if the following signs or symptoms of hypocalcemia develop: abnormal skin sensations, muscle aches, muscle cramping or spasm, seizure activity.

Copyright © 2009 Wolters Kluwer Health.

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