Risedronate Sodium (Page 7 of 9)

14.5 Treatment of Paget’s Disease

The efficacy of risedronate sodium was demonstrated in 2 clinical studies involving 120 men and 65 women. In a double-blind, active-controlled study of patients with moderate-to-severe Paget’s disease (serum alkaline phosphatase levels of at least 2 times the upper limit of normal), patients were treated with risedronate sodium 30 mg daily for 2 months or etidronate disodium 400 mg daily for 6 months. At Day 180, 77% (43/56) of risedronate sodium-treated patients achieved normalization of serum alkaline phosphatase levels, compared to 10.5% (6/57) of patients treated with etidronate disodium (p less than 0.001). At Day 540, 16 months after discontinuation of therapy, 53% (17/32) of risedronate sodium-treated patients and 14% (4/29) of etidronate disodium-treated patients with available data remained in biochemical remission.

During the first 180 days of the active-controlled study, 85% (51/60) of risedronate sodium-treated patients demonstrated a greater than or equal to 75% reduction from baseline in serum alkaline phosphatase excess (difference between measured level and midpoint of the normal range) with 2 months of treatment compared to 20% (12/60) in the etidronate disodium-treated group with 6 months of treatment (p less than 0.001). Changes in serum alkaline phosphatase excess over time (shown in Figure 6) were significant following only 30 days of treatment, with a 36% reduction in serum alkaline phosphatase excess at that time compared to only a 6% reduction seen with etidronate disodium treatment at the same time point (p less than 0.01).
Figure 6 Mean Percent Change from Baseline in Serum Alkaline Phosphatase Excess by Visit

Response to risedronate sodium therapy was similar in patients with mild to very severe Paget’s disease. Table 6 shows the mean percent reduction from baseline at Day 180 in excess serum alkaline phosphatase in patients with mild, moderate, or severe disease.

Table 6 Mean Percent Reduction from Baseline at Day 180 in Total Serum Alkaline Phosphatase Excess by Disease Severity

* Values shown are mean± SEM; ULN = upper limit of normal.
	Risedronate Sodium 30 mg			Etidronate Disodium 400 mg
Subgroup: Baseline Disease Severity (AP)	n	Baseline Serum AP (U/L)*	Mean % Reduction	n	Baseline Serum AP (U/L)*	Mean % Reduction
greater than 2, less than 3x ULN	32	271.6± 5.3	-88.1	22	277.9± 7.45	-44.6
greater than or equal to 3, less than 7x ULN	14	475.3± 28.8	-87.5	25	480.5± 26.44	-35.0
greater than or equal to 7x ULN	8	1336.5± 134.19	-81.8	6	1331.5± 167.58	-47.2

Response to risedronate sodium therapy was similar between patients who had previously received anti-pagetic therapy and those who had not. In the active-controlled study, 4 patients previously non-responsive to 1 or more courses of anti-pagetic therapy (calcitonin, etidronate disodium) responded to treatment with risedronate sodium 30 mg daily (defined by at least a 30% change from baseline). Each of these patients achieved at least 90% reduction from baseline in serum alkaline phosphatase excess, with 3 patients achieving normalization of serum alkaline phosphatase levels.

Histomorphometry of the bone was studied in 14 patients with bone biopsies: 9 patients had biopsies from pagetic bone lesions and 5 patients from non-pagetic bone. Bone biopsy results in non-pagetic bone did not reveal osteomalacia, impairment of bone remodeling, or induction of a significant decline in bone turnover in patients treated with risedronate sodium.

16 HOW SUPPLIED/STORAGE AND HANDLING

Risedronate sodium tablets, USP are available as follows:

5 mg film-coated, round, yellow tablets debossed ‘5’ on one side and ‘S’ on other side.

Bottles of 30 with Child-resistant Cap, DC 47335-666-83

Bottles of 100 with Child-resistant Cap, NDC 47335-666-88

Bottles of 100, NDC 47335-666-08

Bottles of 1000, NDC 47335-666-18

30 mg film-coated, round, white tablets debossed ‘667’ on one side and ‘S’ on other side.

Bottles of 30 with Child-resistant Cap, NDC 47335-667-83

Bottles of 100 with Child-resistant Cap, NDC 47335-667-88

Bottles of 100, NDC 47335-667-08

Bottles of 1000, NDC 47335-667-18

35 mg film-coated, round, brown tablets debossed ‘668’ on one side and ‘S’ on other side.

Unit-dose blister package of 4……………………..… NDC 47335-668-68

Unit-dose blister package of 12……………………… NDC 47335-668-62

75 mg film-coated, round, pink tablets debossed ‘727’ on one side and ‘S’ on other side.

Unit-dose blister package of 2…………………..…… NDC 47335-727-98

150 mg film-coated, round, blue tablets debossed ‘928’ on one side and ‘S’ on other side.

Unit-dose blister package of 1..……………………… NDC 47335-928-60

Unit-dose blister package of 3..……………………… NDC 47335-928-67

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F) [see USP Controlled Room Temperature].

Dispense in well-closed containers as defined in USP.

17 PATIENT COUNSELING INFORMATION

See FDA-approved patient labeling (Medication Guide)

Instruct patients to read the Medication Guide before starting therapy with risedronate sodium tablets and to re-read it each time the prescription is renewed.

Instruct patients that risedronate sodium delayed-release tablets and risedronate sodium tablets contain the same active ingredient and if they are taking risedronate sodium delayed-release tablets, they should not take risedronate sodium tablets [see Warnings and Precautions (5.1)].

Instruct patients to pay particular attention to the dosing instructions as clinical benefits may be compromised by failure to take the drug according to instructions. Specifically, risedronate sodium tablets should be taken at least 30 minutes before the first food or drink of the day other than water.

Instruct patients to take risedronate sodium tablets while in an upright position (sitting or standing) with a full glass of plain water (6 to 8 ounces) to facilitate delivery to the stomach, and thus reduce the potential for esophageal irritation.

Instruct patients not to lie down for 30 minutes after taking the medication [see Warnings and Precautions (5.1) ].

Instruct patients not to chew or suck on the tablet because of a potential for oropharyngeal irritation.

Instruct patients that if they develop symptoms of esophageal disease (such as difficulty or pain upon swallowing, retrosternal pain or severe persistent or worsening heartburn) they should consult their physician before continuing risedronate sodium tablets.

Instruct patients about missing risedronate sodium tablets doses as follows:

• If a dose of risedronate sodium tablet 35 mg once-a-week is missed, they should take 1 tablet on the morning after they remember and return to taking 1 tablet once-a-week, as originally scheduled on their chosen day. Patients should not take 2 tablets on the same day.
• If one or both tablets of risedronate sodium tablet 75 mg on two consecutive days per month are missed, and the next month’s scheduled doses are more than 7 days away, the patient should be instructed as follows:
  • If both tablets are missed, take one risedronate sodium tablet 75 mg in the morning after the day it is remembered and then the other tablet on the next consecutive morning.
  • If only one risedronate sodium tablet 75 mg is missed, take the missed tablet in the morning after the day it is remembered.
  • Patients should then return to taking their risedronate sodium tablets 75 mg on two consecutive days per month as originally scheduled. Patients should not take more than two 75 mg tablets within 7 days.
• If one or both tablets of risedronate sodium 75 mg on two consecutive days per month are missed, and the next month’s scheduled doses are within 7 days, patients should wait until their next month’s scheduled doses and then continue taking risedronate sodium tablet 75 mg on two consecutive days per month as originally scheduled.
• If the dose of risedronate sodium tablet 150 mg once-a-month is missed, and the next month’s scheduled dose is more than 7 days away, the patient should be instructed to take the missed tablet in the morning after the day it is remembered. Patients should then return to taking their risedronate sodium tablets 150 mg once-a-month as originally scheduled. Patients should not take more than one 150 mg tablet within 7 days.
• If the dose of risedronate sodium tablet 150 mg once-a-month is missed, and the next month’s scheduled dose is within 7 days, patients should wait until their next month’s scheduled dose and then continue taking risedronate sodium tablet 150 mg once-a-month as originally scheduled.

Instruct patients to take supplemental calcium and vitamin D if dietary intake is inadequate [see Warnings and Precautions (5.3) ]. Weight-bearing exercise should be considered along with the modification of certain behavioral factors, such as excessive cigarette smoking, and/or alcohol consumption, if these factors exist.

Instruct patients to take calcium supplements or calcium-, aluminum-, and magnesium-containing medications at a different time of the day than risedronate sodium tablets as these medications may interfere with the absorption of risedronate sodium tablets.

Remind patients to give all of their healthcare providers an accurate medication history. Instruct patients to tell all of their healthcare providers that they are taking risedronate sodium tablets. Patients should be instructed that any time they have a medical problem they think may be from risedronate sodium tablets, they should talk to their doctor.

Dispense with Medication Guide available at: https://www.sunpharma.com/usa/products