Sensipar Information
Sensipar () Indications And Usage
Sensipar () is indicated for the treatment of severe hypercalcemia in patients with primary HPT who are unable to undergo parathyroidectomy
Sensipar () Dosage And Administration
Sensipar () tablets should be taken whole and should not be divided. Sensipar () should be taken with food or shortly after a meal.
Dosage must be individualized.
Sensipar () Dosage Forms And Strengths
Sensipar () tablets are formulated as light-green, film-coated, oval-shaped tablets marked with “AMG” on one side and “30” or “60” or “90” on the opposite side of the 30 mg, 60 mg, or 90 mg strengths, respectively.
Sensipar () Contraindications
Hypocalcemia: Sensipar () treatment should not be initiated if serum calcium is less than the lower limit of the normal range .
Sensipar () Warnings And Precautions
Sensipar () lowers serum calcium and, therefore, patients should be carefully monitored for the occurrence of hypocalcemia. Potential manifestations of hypocalcemia include paresthesias, myalgias, muscle cramping, tetany, and convulsions.
Serum calcium should be measured within 1 week after initiation or dose adjustment of Sensipar () . Once the maintenance dose has been established, serum calcium should be measured approximately monthly.
If serum calcium falls below 8.4 mg/dL but remains above 7.5 mg/dL, or if symptoms of hypocalcemia occur, calcium-containing phosphate binders and/or vitamin D sterols can be used to raise serum calcium. If serum calcium falls below 7.5 mg/dL, or if symptoms of hypocalcemia persist and the dose of vitamin D cannot be increased, withhold administration of Sensipar () until serum calcium levels reach 8.0 mg/dL and/or symptoms of hypocalcemia have resolved. Treatment should be reinitiated using the next lowest dose of Sensipar () .
In 26-week studies of patients with CKD on dialysis, 66% of patients receiving Sensipar () compared with 25% of patients receiving placebo developed at least one serum calcium value
Sensipar () is not indicated for patients with CKD not on dialysis. In patients with secondary HPT and CKD not on dialysis, the long term safety and efficacy of Sensipar () have not been established. Clinical studies indicate that Sensipar () -treated patients with CKD not on dialysis have an increased risk for hypocalcemia compared with Sensipar () -treated patients with CKD on dialysis, which may be due to lower baseline calcium levels. In a phase 3 study of 32 weeks duration and including 404 patients with CKD not on dialysis (302 cinacalcet, 102 placebo), in which the median dose for cinacalcet was 60 mg per day at the completion of the study, 80% of Sensipar () -treated patients experienced at least one serum calcium value
In clinical studies, seizures (primarily generalized or tonic-clonic) were observed in 1.4% (43/3049) of Sensipar () -treated patients and 0.7% (5/687) of placebo-treated patients. While the basis for the reported difference in seizure rate is not clear, the threshold for seizures is lowered by significant reductions in serum calcium levels. Therefore, serum calcium levels should be closely monitored in patients receiving Sensipar () , particularly in patients with a history of a seizure disorder .
Sensipar () Adverse Reactions
The following adverse reactions have been identified during postapproval use of Sensipar () . Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Rash, hypersensitivity reactions (including angioedema and urticaria), diarrhea, and myalgia have been identified as adverse reactions during postapproval use of Sensipar () . Isolated, idiosyncratic cases of hypotension, worsening heart failure, and/or arrhythmia have been reported in Sensipar () -treated patients with impaired cardiac function in postmarketing safety surveillance.
Sensipar () Use In Specific Populations
In pregnant female rats given oral gavage doses of 2, 25, 50 mg/kg/day cinacalcet during gestation, no teratogenicity was observed at doses up to 50 mg/kg/day (exposure 4 times those resulting with a human oral dose of 180 mg/day based on Area Under the Curve [AUC] comparison). Decreased fetal body weights were observed at all doses (less than 1 to 4 times a human oral dose of 180 mg/day based on AUC comparison) in conjunction with maternal toxicity (decreased food consumption and body weight gain).
In pregnant female rabbits given oral gavage doses of 2, 12, 25 mg/kg/day cinacalcet during gestation, no adverse fetal effects were observed (exposures less than with a human oral dose of 180 mg/day based on AUC comparisons). Reductions in maternal food consumption and body weight gain were seen at doses of 12 and 25 mg/kg/day. Sensipar () has been shown to cross the placental barrier in rabbits.
In pregnant rats given oral gavage doses of 5, 15, 25 mg/kg/day cinacalcet during gestation through lactation, no adverse fetal or pup (post-weaning) effects were observed at 5 mg/kg/day (exposures less than with a human therapeutic dose of 180 mg/day based on AUC comparisons). Higher doses of 15 and 25 mg/kg/day cinacalcet (exposures 2 to 3 times a human oral dose of 180 mg/day based on AUC comparisons) were accompanied by maternal signs of hypocalcemia (periparturient mortality and early postnatal pup loss), and reductions in postnatal maternal and pup body-weight gain.
There are no adequate and well-controlled studies of Sensipar () in pregnant women. Sensipar () should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Women who become pregnant during Sensipar () treatment are encouraged to enroll in Amgen’s Pregnancy Surveillance Program. Patients or their physicians should call 1-800-77-AMGEN (1-800-772-6436) to enroll.
Sensipar () Overdosage
Doses titrated up to 300 mg once daily have been safely administered to patients on dialysis. Overdosage of Sensipar () may lead to hypocalcemia. In the event of overdosage, patients should be monitored for signs and symptoms of hypocalcemia and appropriate measures taken to correct serum calcium levels .
Since Sensipar () is highly protein bound, hemodialysis is not an effective treatment for overdosage of Sensipar () .
Sensipar () Description
Sensipar () (cinacalcet) is a calcimimetic agent that increases the sensitivity of the calcium-sensing receptor to activation by extracellular calcium. Sensipar () tablets contain the hydrochloride salt of cinacalcet. Its empirical formula is CHFN·HCl with a molecular weight of 393.9 g/mol (hydrochloride salt) and 357.4 g/mol (free base). It has one chiral center having an R-absolute configuration. The R-enantiomer is the more potent enantiomer and has been shown to be responsible for pharmacodynamic activity.
The hydrochloride salt of cinacalcet is a white to off-white, crystalline solid that is soluble in methanol or 95% ethanol and slightly soluble in water.
Sensipar () tablets are formulated as light-green, film-coated, oval-shaped tablets for oral administration in strengths of 30 mg, 60 mg, and 90 mg of cinacalcet as the free base equivalent (33 mg, 66 mg, and 99 mg as the hydrochloride salt, respectively).
The hydrochloride salt of cinacalcet is described chemically as N-[1-(R)-(-)-(1-naphthyl)ethyl]-3-[3-(trifluoromethyl)phenyl]-1-aminopropane hydrochloride and has the following structural formula:
The following are the inactive ingredients in Sensipar () tablets: pre-gelatinized starch, microcrystalline cellulose, povidone, crospovidone, colloidal silicon dioxide and magnesium stearate. Tablets are coated with color (OpadryII green), clear film coat (Opadryclear), and carnauba wax.
Sensipar () Clinical Pharmacology
Secondary HPT in patients with CKD is a progressive disease, associated with increases in PTH levels and derangements in calcium and phosphorus metabolism. Increased PTH stimulates osteoclastic activity resulting in cortical bone resorption and marrow fibrosis. The goals of treatment of secondary HPT are to lower the levels of PTH, calcium, and phosphorus in the blood in order to prevent progressive bone disease and the systemic consequences of disordered mineral metabolism. Reductions in PTH are associated with a decrease in bone turnover and bone fibrosis in patients with CKD on dialysis and uncontrolled secondary HPT.
The calcium-sensing receptor on the surface of the chief cell of the parathyroid gland is the principal regulator of PTH synthesis and secretion. Sensipar () directly lowers PTH levels by increasing the sensitivity of the calcium-sensing receptor to extracellular calcium. The reduction in PTH is associated with a concomitant decrease in serum calcium levels. Measurements of PTH during the Sensipar () studies were obtained using the Nichols IRMA.
Sensipar () Clinical Studies
Three 6-month, multicenter, randomized, double-blind, placebo-controlled clinical studies of similar design were conducted in patients with CKD on dialysis. A total of 665 patients were randomized to Sensipar () and 471 patients to placebo. The mean age of the patients was 54 years, 62% were male, and 52% were Caucasian. The average baseline iPTH level by the Nichols IRMA was 712 pg/mL, with 26% of the patients having a baseline iPTH level > 800 pg/mL. The mean baseline Ca x P ion product was 61 mg/dL. The average duration of dialysis prior to study enrollment was 67 months. Ninety-six percent of patients were on hemodialysis and 4% on peritoneal dialysis. At study entry, 66% of the patients were receiving vitamin D sterols and 93% were receiving phosphate binders. Sensipar () (or placebo) was initiated at a dose of 30 mg once daily and titrated every 3 or 4 weeks to a maximum dose of 180 mg once daily to achieve an iPTH of ≤ 250 pg/mL. The dose was not increased if a patient had any of the following: iPTH ≤ 200 pg/mL, serum calcium
Similar results were observed when either the iPTH or biointact PTH (biPTH) assay was used to measure PTH levels in CKD patients on dialysis; treatment with cinacalcet did not alter the relationship between iPTH and biPTH.
Reductions in iPTH and Ca x P were maintained for up to 12 months of treatment. Sensipar () decreased iPTH and Ca x P levels regardless of disease severity (i.e., baseline iPTH value), duration of dialysis, and whether or not vitamin D sterols were administered. Approximately 60% of patients with mild (iPTH ≥ 300 to ≤ 500 pg/mL), 41% with moderate (iPTH > 500 to 800 pg/mL), and 11% with severe (iPTH > 800 pg/mL) secondary HPT achieved a mean iPTH value of ≤ 250 pg/mL. Plasma iPTH levels were measured using the Nichols IRMA.
Twenty-nine patients with Parathyroid Carcinoma were enrolled in a single-arm, open-label study. The study consisted of two phases, a dose-titration phase and a maintenance phase. Patients initially received 30 mg cinacalcet twice daily and then were titrated every 2 weeks to a maximum dose of 90 mg four times daily. Dosage escalation during the variable-length (2 to 16 weeks) titration phase continued until the serum calcium concentration was ≤ 10 mg/dL (2.5 mmol/L), the patient reached the highest possible dosage, or adverse events precluded further dosage increases.
Twenty-nine patients entered the study. The median exposure to cinacalcet was 229 days (range: 1 to 1051). At baseline the mean (SE) serum calcium was 14.1 (0.4) mg/dL. At the end of the titration phase, the mean (SE) serum calcium was 12.4 (0.5) mg/dL, which is a mean reduction of 1.7 (0.6) mg/dL from baseline. Figure 3 illustrates mean serum calcium (mg/dL) over time for all patients still on study at each time point from the beginning of titration to study visit week 80. Daily dose during the study ranged from 30 mg twice daily to 90 mg four times daily.
Seventeen patients with severe hypercalcemia due to primary HPT, who had failed or had contraindications to parathyroidectomy, participated in an open-label study. The study consisted of two phases, a dose-titration phase and a maintenance phase. In this trial severe hypercalcemia was defined as a screening serum calcium level of > 12.5 mg/dL. Patients initially received 30 mg cinacalcet twice daily and then were titrated every 2 weeks to a maximum dose of 90 mg 4 times daily. Dosage escalation during the variable-length (2 to 16 weeks) titration phase continued until the serum calcium concentration was ≤ 10 mg/dL (2.5 mmol/L), the patient reached the highest possible dosage, or adverse events precluded further dosage increases.
Seventeen patients entered the study. The median exposure to cinacalcet was 270 days (range: 32 to 1,105). At baseline the mean (SE) serum calcium was 12.7 (0.2) mg/dL. At the end of the titration phase the mean (SE) serum calcium was 10.4 (0.3) mg/dL, which is a mean reduction of 2.3 (0.3) mg/dL from baseline. Figure 4 illustrates mean serum calcium (mg/dL) over time for all patients still on study at each time point from the beginning of titration to study visit week 80. Daily dose during the study ranged from 30 mg twice a day to 90 mg four times a day.
Sensipar () How Supplied/storage And Handling
Sensipar () 30 mg tablets are formulated as light-green, film-coated, oval-shaped tablets marked with “AMG” on one side and “30” on the opposite side, packaged in bottles of 30 tablets. (NDC 55513-073-30)
Sensipar () 60 mg tablets are formulated as light-green, film-coated, oval-shaped tablets marked with “AMG” on one side and “60” on the opposite side, packaged in bottles of 30 tablets. (NDC 55513-074-30)
Sensipar () 90 mg tablets are formulated as light-green, film-coated, oval-shaped tablets marked with “AMG” on one side and “90” on the opposite side, packaged in bottles of 30 tablets. (NDC 55513-075-30)
Store at 25ºC (77ºF); excursions permitted from 15°C to 30ºC (59°F to 86ºF). [See USP controlled room temperature].
Sensipar ()
Sensipar () Package Label - Principal Display Panel - Tablet, Mg
AMGEN
NDC 55513-073-30
Sensipar ()
(cinacalcet HCI) Tablets
30 mg
Rx Only
30 tablets
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).
See USP controlled room temperature.
Dispense in tight, light-resistant container per USP.
Dosage: See Package Insert.
2011 © Amgen Inc. This product, or its use, may be covered by US Patents including US Patent Nos. 6,313,146; 6,211,244; 6,031,003; 6,011,068 and 7,829,595 in addition to others, including patents pending.
Lot
Exp.
2000004019
Distributed by: Amgen, One Amgen Center Drive, Thousand Oaks, CA 91320-1799
Made in Japan
Sensipar () Package Label - Principal Display Panel - Tablet, Mg
AMGEN
NDC 55513-074-30
Sensipar ()
(cinacalcet HCI) Tablets
60 mg
Rx Only
30 tablets
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).
See USP controlled room temperature.
Dispense in tight, light-resistant container per USP.
Dosage: See Package Insert.
2011 © Amgen Inc. This product, or its use, may be covered by US Patents including US Patent Nos. 6,313,146; 6,211,244; 6,031,003; 6,011,068 and 7,829,595 in addition to others, including patents pending.
Lot
Exp.
2000004020
Distributed by: Amgen, One Amgen Center Drive, Thousand Oaks, CA 91320-1799
Made in Japan
Sensipar () Package Label - Principal Display Panel - Tablet, Mg
AMGEN
NDC 55513-075-30
Sensipar ()
(cinacalcet HCI) Tablets
90 mg
Rx Only
30 tablets
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).
See USP controlled room temperature.
Dispense in tight, light-resistant container per USP.
Dosage: See Package Insert.
2011 © Amgen Inc. This product, or its use, may be covered by US Patents including US Patent Nos. 6,313,146; 6,211,244; 6,031,003; 6,011,068 and 7,829,595 in addition to others, including patents pending.
Lot
Exp.
2000004021
Distributed by: Amgen, One Amgen Center Drive, Thousand Oaks, CA 91320-1799
Made in Japan
