Sensipar

cinacalcet hydrochloride

Mimpara (UK), Sensipar

Pharmacologic class: Calcimimetic

Therapeutic class: Endocrine and metabolic agent

Pregnancy risk category C

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.

cinacalcet

(sin-a-kal-set) ,

Sensipar

(trade name)

Classification

Therapeutic: hypocalcemics
Pharmacologic: calcimimetic agents
Pregnancy Category: C

Indications

Secondary hyperparathyroidism in patients with chronic kidney disease (CKD) on dialysis.Hypercalcemia caused by parathyroid carcinoma.Severe hypercalcemia in patients with primary hyperparathyroidism in patients who are unable to undergo parathyroidectomy.

Action

Increases sensitivity of calcium-sensing receptors located on the surface of chief cells of parathyroid gland to levels of extracellular calcium. This decreases parathyroid hormone production with resultant decrease in serum calcium.

Therapeutic effects

Decreased bone turnover and fibrosis.
Decreased serum calcium.

Pharmacokinetics

Absorption: Well absorbed following oral administration, absorption is enhanced by food and further enhanced by a high fat meal.
Distribution: Unknown.
Protein Binding: 93–97%.
Metabolism and Excretion: Highly metabolized by CYP3A4, CYP2D6, and CYP1A2 enzyme systems; 80% excreted in urine as metabolites, 15% in feces.
Half-life: 30–40 hr.

Time/action profile (effect on PTH levels)

ROUTEONSETPEAKDURATION
POrapid2–6 hr6–12 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Hypocalcemia; Lactation: Discontinue drug or bottle-feed.
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 to severe hepatic impairment; Obstetric: Use only if benefits justify risks to fetus; Pediatric: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • seizures

Gastrointestinal

  • nausea (most frequent)
  • vomiting (most frequent)

Fluid and Electrolyte

  • hypocalcemia

Metabolic

  • adynamic bone disease

Interactions

Drug-Drug interaction

Inhibits CYP2D6 and may ↑ levels of flecainide, vinblastine, thioridazine, metoprolol, carvedilol, and most tricyclic antidepressants ; dose adjustments may be necessary.Blood levels are ↑ by strong CYP3A4 inhibitors including ketoconazole, itraconazole, and erythromycin ; monitoring and dose adjustment may be necessary.

Route/Dosage

Oral (Adults) Secondary hyperparathyroidism in CKD patients on dialysis—30 mg once daily; may ↑ dose every 2–4 wk (dose range 30–180 mg once daily) based on iPTH levels; Parathyroid carcinoma or primary hyperparathyroidism—30 mg twice daily; may titrate every 2–4 wk up to 90 mg 3–4 times daily based on serum calcium levels.

Availability

Tablets: 30 mg, 60 mg, 90 mg

Nursing implications

Nursing 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.
  • Lab Test Considerations: Monitor serum calcium and phosphorous 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. Re-initiate 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.
    • Monitor liver function tests in patients with moderate to severe hepatic impairment during therapy.

Potential Nursing Diagnoses

Deficient knowledge, related to medication regimen (Patient/Family Teaching)

Implementation

  • Cinacalcet may be used alone or in combination with vitamin D and/or phosphate binders.
  • Oral: Administer with food or shortly after a meal. Take tablets whole, 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 to health care professional promptly.
  • Emphasize the importance of follow-up lab tests to monitor safely and efficacy.

Evaluation/Desired Outcomes

  • Decreased serum calcium levels.

Sensipar

a trademark for cinacalcet.
References in periodicals archive ?
Soft but Reliable Growth: Growth of a number of established products, XGEVA (bone metastases), Prolia (osteoporosis), Nplate (thrombocytopenia), Vectibix (metastatic colorectal cancer), and Sensipar (secondary hyperparathyroidism), should help to offset some of the risk of anticipated branded and biosimilar competition against Neulasta and Epogen and existing competition against Neupogen.
He has been involved in many product launches including serving as the global lead for Amgen's launch of Sensipar.
examined four top-selling orphan drugs (Lidoderm, Provigil, Sensipar, and Gleevdc) and demonstrated that the rate of growth in usage of these drugs for non-orphan conditions was greater than the intended orphan usage.
The law ensures that Amgen, the world's largest biotechnology business, will have two years to sell its dialysis pill Sensipar without any limits on what Medicare has to pay for it, even though the fiscal cliff bill is supposed to save $4.
Nader added: "It is especially notable that our royalty-based portfolio continues to provide an important financial foundation for our business, including our Sensipar royalty agreement with Amgen that is now generating more than $64 million in annual cash flows that are expected to increase to more than $100 million after repayment of the Amgen royalty advance.
The bone card also pays whatever is left over on my Sensipar.
According to company shareholder reports, Amgen's other drugs, including the dialysis related drugs Sensipar and Aranesp, bring in another $11.
The oral medicines used by dialysis patients include Amgen's Sensipar and two products from Genzyme, Renagel and Renvela, which cut phosphate levels.
5 mg to prevent bone disease; Nephro-Vite one tablet daily; Normodyne 200 mg 2x/day; Sensipar 60 mg for hyperparathyroidism in dialysis patients; Venofer 50 mg IV 1x/week; and Zemplar 7 mcg IV to prevent secondary hyperparathyroidism.
Worldwide, sales of Sensipar more than doubled, to 119 percent, making $79 million.
NPS developed the drug Sensipar to treat thyroid and kidney problems, but Sensipar is marketed by Amgen, NPS is presently seeking FDA approval on Preos, an osteoporosis drug.