Sensipar

Secondary Hyperparathyroidism

Sensipar is indicated for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on dialysis [see Clinical Studies].

Sensipar is not indicated for use in adult patients with CKD who are not on dialysis because of an increased risk of hypocalcemia [see WARNINGS AND PRECAUTIONS].

Parathyroid Carcinoma

Sensipar is indicated for the treatment of hypercalcemia in adult patients with Parathyroid Carcinoma [see Clinical Studies].

Primary Hyperparathyroidism

Sensipar is indicated for the treatment of hypercalcemia in adult patients with primary HPT for whom parathyroidectomy would be indicated on the basis of serum calcium levels, but who are unable to undergo parathyroidectomy [see Clinical Studies ].

Serious side effects have been reported. See the Drug Precautions section.

Common side effects include:

• nausea
• vomiting
• diarrhea
• numbness around the mouth, feet, or fingertips

This is not a complete list of side effects. Ask your doctor or pharmacist for more information.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

It is not known if Sensipar crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with the use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using Sensipar.

• If you have an allergy to cinacalcet or any other part of Sensipar (cinacalcet).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have low calcium levels.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Sensipar with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine lowers blood calcium levels. Life-threatening and fatal events linked to low blood calcium levels have happened in people taking Sensipar. Talk with your doctor.
• Worsening of heart failure can rarely occur.
• This medicine is not approved for use in children. A death has happened in a child with severe low blood calcium levels. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Feeling tired or weak.
• Headache.
• Hard stools (constipation).
• Loose stools (diarrhea).
• Not hungry.
• Dizziness.
• Belly pain.
• Cough.
• Signs of a common cold.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about Sensipar, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Sensipar. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Sensipar.

Review Date: October 4, 2017

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 C22H22F3N•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:

Inactive Ingredients

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 (Opadry® II green), clear film coat (Opadry® clear), and carnauba wax.

      Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease on Dialysis

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 product was 61 mg2/dL2. 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 < 7.8 mg/dL, or any symptoms of hypocalcemia. If a patient experienced symptoms of hypocalcemia or had a serum calcium < 8.4 mg/dL, calcium supplements and/or calcium-based phosphate binders could be increased. If these measures were insufficient, the vitamin D dose could be increased. Approximately 70% of patients in the Sensipar arm and 80% of the patients in the placebo arm completed the 6-month studies. In the primary efficacy analysis, 40% of the patients on Sensipar and 5% of placebo-treated patients achieved an iPTH ≤ 250 pg/mL (p < 0.001) (Table 7, Figure 1). These studies showed that Sensipar reduced iPTH while lowering Ca x P, calcium, and phosphorus levels (Table 7, Figure 2). The median dose of Sensipar at the completion of the studies was 90 mg. Patients with milder disease typically required lower doses.

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.

Figure 1. Mean (SE) iPTH Values (Pooled Phase 3 Studies)

Data are presented for patients who completed the studies; Placebo (n = 342), Sensipar (n = 439).

Figure 2. Mean (SE) Ca x P Values (Pooled Phase 3 Studies)

Data are presented for patients who completed the studies; Placebo (n = 342), Sensipar (n = 439).

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.

      Parathyroid Carcinoma

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.

Figure 3. Serum Calcium Values in Patients With Parathyroid Carcinoma Receiving Sensipar at Baseline, Titration, and Maintenance Phase

n = Number of patients with non-missing values at the timepoint.

End of Titration (EOT) phase could occur at any visit from week 2 to 16.  Patients at EOT are those who completed titration.

      Patients with Hypercalcemia Due to Primary Hyperparathyroidism

Seventeen patients with severe hypercalcemia due to primary HPT, who had failed or had contraindications to parathyroidectomy, participated in an open-label, single-arm 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.

Figure 4. Mean Serum Calcium (SE) at Baseline, End of Titration, and Scheduled Maintenance Visits (Patients with Severe intractable primary HPT)

n = Number of patients with non-missing values at the timepoint.

End of Titration (EOT) phase could occur at any visit from week 2 to 16.  Patients at EOT are those who completed titration.

Sixty-seven patients with primary HPT who met criteria for parathyroidectomy on the basis of corrected total serum calcium (> 11.3 mg/dL [2.82 mmol/L] and ≤ 12.5 mg/dL [3.12 mmol/L]), but who were unable to undergo parathyroidectomy participated in a randomized, double-blind, placebo-controlled study.  A total of 33 patients were randomized to Sensipar and 34 patients randomized to placebo.  The mean age of the patients was 72 years, 52% were female, 61% were Caucasian, and 5% were Blacks.  The study started with a 12-week titration phase, followed by a 16-week efficacy assessment phase.  Cinacalcet was initiated at a dose of 30 mg twice daily and titrated to maintain a corrected total serum calcium concentration within the normal range.  During the efficacy period a significantly higher percentage of cinacalcet treated patients compared with the placebo treated patients achieved mean corrected total serum calcium concentration (≤ 10.3 mg/dL [2.57 mmol/L], 75.8% vs 0%, p < 0.001) and ≥ 1 mg/dL [0.25 mmol/L] decrease from baseline in mean corrected total serum calcium concentration (84.8% vs 5.9%, p < 0.001).  The median dose of Sensipar at the completion of the study was 60 mg/day. 

You should not use Sensipar if you are allergic to cinacalcet, or if you have:

• low levels of calcium in your blood (hypocalcemia).

To make sure Sensipar is safe for you, tell your doctor if you have ever had:

• high or low blood pressure;

• heart disease, heart failure, heart rhythm disorder;

• personal or family history of long QT syndrome;

• a stomach ulcer or severe vomiting;

• liver disease;

• seizures; or

• if you have kidney disease and you are not on dialysis.

It is not known whether Sensipar will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether cinacalcet passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are taking this medicine.

Sensipar is not approved for use by anyone younger than 18 years old.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Many drugs can interact with cinacalcet. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide. Tell your doctor about all medicines you use, and those you start or stop using during your treatment with Sensipar. Give a list of all your medicines to any healthcare provider who treats you.

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Cinacalcet works best if you take it with food or shortly after eating a meal.

Do not crush or break a cinacalcet tablet. Swallow the pill whole.

To be sure your calcium and phosphorous levels do not get too low, your blood will need to be tested 1 week after you start taking cinacalcet or whenever your dose is changed. You may also need blood tests on a regular basis during treatment.

Store at room temperature away from moisture, light, and heat.

Many drugs can interact with cinacalcet. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide. Tell your doctor about all your current medicines and any medicine you start or stop using.