Prescription Drug Information: Alendronate Sodium (Page 6 of 8)

14.2 Prevention of Osteoporosis in Postmenopausal Women

Daily Dosing
Prevention of bone loss was demonstrated in two double-blind, placebo-controlled studies of postmenopausal women 40 to 60 years of age. One thousand six hundred nine patients (alendronate 5 mg/day; n=498) who were at least six months postmenopausal were entered into a two-year study without regard to their baseline BMD. In the other study, 447 patients (alendronate 5 mg/day; n=88), who were between six months and three years postmenopause, were treated for up to three years. In the placebo-treated patients BMD losses of approximately 1% per year were seen at the spine, hip (femoral neck and trochanter) and total body. In contrast, alendronate 5 mg/day prevented bone loss in the majority of patients and induced significant increases in mean bone mass at each of these sites (see Figure 4). In addition, alendronate 5 mg/day reduced the rate of bone loss at the forearm by approximately half relative to placebo. Alendronate 5 mg/day was similarly effective in this population regardless of age, time since menopause, race and baseline rate of bone turnover.
Figure 4:

Figure 4
(click image for full-size original)

Bone Histology

Bone histology was normal in the 28 patients biopsied at the end of three years who received alendronate at doses of up to 10 mg/day.
Weekly DosingThe therapeutic equivalence of once weekly alendronate 35 mg (n=362) and alendronate 5 mg daily (n=361) was demonstrated in a one-year, double-blind, multicenter study of postmenopausal women without osteoporosis. In the primary analysis of completers, the mean increases from baseline in lumbar spine BMD at one year were 2.9% (2.6, 3.2%; 95% CI) in the 35 mg once-weekly group (n=307) and 3.2% (2.9, 3.5%; 95% CI) in the 5 mg daily group (n=298). The two treatment groups were also similar with regard to BMD increases at other skeletal sites. The results of the intention-to-treat analysis were consistent with the primary analysis of completers.

14.3 Treatment to Increase Bone Mass in Men with Osteoporosis

The efficacy of alendronate sodium in men with hypogonadal or idiopathic osteoporosis was demonstrated in two clinical studies.
Daily Dosing
A two-year, double-blind, placebo-controlled, multicenter study of alendronate 10 mg once daily enrolled a total of 241 men between the ages of 31 and 87 (mean, 63). All patients in the trial had either a BMD T-score less than or equal to -2 at the femoral neck and less than or equal to -1 at the lumbar spine, or a baseline osteoporotic fracture and a BMD T-score less than or equal to -1 at the femoral neck. At two years, the mean increases relative to placebo in BMD in men receiving alendronate 10 mg/day were significant at the following sites: lumbar spine, 5.3%; femoral neck, 2.6%; trochanter, 3.1%; and total body, 1.6%. Treatment with alendronate sodium also reduced height loss (alendronate sodium, -0.6 mm vs. placebo, -2.4 mm).
Weekly Dosing
A one-year, double-blind, placebo-controlled, multicenter study of once weekly alendronate 70 mg enrolled a total of 167 men between the ages of 38 and 91 (mean, 66). Patients in the study had either a BMD T-score less than or equal to -2 at the femoral neck and less than or equal to -1 at the lumbar spine, or a BMD T-score less than or equal to -2 at the lumbar spine and less than or equal to -1 at the femoral neck, or a baseline osteoporotic fracture and a BMD T-score less than or equal to -1 at the femoral neck. At one year, the mean increases relative to placebo in BMD in men receiving alendronate 70 mg once weekly were significant at the following sites: lumbar spine, 2.8%; femoral neck, 1.9%; trochanter, 2%; and total body, 1.2%. These increases in BMD were similar to those seen at one year in the 10 mg once-daily study.
In both studies, BMD responses were similar regardless of age (greater than or equal to 65 years vs. less than 65 years), gonadal function (baseline testosterone less than 9 ng/dL vs. greater than or equal to 9 ng/dL), or baseline BMD (femoral neck and lumbar spine T-score less than or equal to -2.5 vs. greater than -2.5).

14.4 Treatment of Glucocorticoid-Induced Osteoporosis

The efficacy of alendronate 5 and 10 mg once daily in men and women receiving glucocorticoids (at least 7.5 mg/day of prednisone or equivalent) was demonstrated in two, one-year, double-blind, randomized, placebo-controlled, multicenter studies of virtually identical design, one performed in the United States and the other in 15 different countries (Multinational [which also included alendronate 2.5 mg/day]). These studies enrolled 232 and 328 patients, respectively, between the ages of 17 and 83 with a variety of glucocorticoid-requiring diseases. Patients received supplemental calcium and vitamin D. Figure 5 shows the mean increases relative to placebo in BMD of the lumbar spine, femoral neck, and trochanter in patients receiving alendronate 5 mg/day for each study.Figure 5:

Figure 5
(click image for full-size original)

After one year, significant increases relative to placebo in BMD were seen in the combined studies at each of these sites in patients who received alendronate 5 mg/day. In the placebo-treated patients, a significant decrease in BMD occurred at the femoral neck (-1.2%), and smaller decreases were seen at the lumbar spine and trochanter. Total body BMD was maintained with alendronate 5 mg/day. The increases in BMD with alendronate 10 mg/day were similar to those with alendronate 5 mg/day in all patients except for postmenopausal women not receiving estrogen therapy. In these women, the increases (relative to placebo) with alendronate 10 mg/day were greater than those with alendronate 5 mg/day at the lumbar spine (4.1% vs. 1.6%) and trochanter (2.8% vs. 1.7%), but not at other sites. Alendronate sodium was effective regardless of dose or duration of glucocorticoid use. In addition, alendronate sodium was similarly effective regardless of age (less than 65 vs. greater than or equal to 65 years), race (Caucasian vs. other races), gender, underlying disease, baseline BMD, baseline bone turnover, and use with a variety of common medications.
Bone histology was normal in the 49 patients biopsied at the end of one year who received alendronate at doses of up to 10 mg/day.
Of the original 560 patients in these studies, 208 patients who remained on at least 7.5 mg/day of prednisone or equivalent continued into a one-year double-blind extension. After two years of treatment, spine BMD increased by 3.7% and 5% relative to placebo with alendronate 5 and 10 mg/day, respectively. Significant increases in BMD (relative to placebo) were also observed at the femoral neck, trochanter, and total body.
After one year, 2.3% of patients treated with alendronate 5 or 10 mg/day (pooled) vs. 3.7% of those treated with placebo experienced a new vertebral fracture (not significant). However, in the population studied for two years, treatment with alendronate (pooled dosage groups: 5 or 10 mg for two years or 2.5 mg for one year followed by 10 mg for one year) significantly reduced the incidence of patients with a new vertebral fracture (alendronate 0.7% vs. placebo 6.8%).

14.5 Treatment of Paget’s Disease of Bone

The efficacy of alendronate 40 mg once daily for six months was demonstrated in two double-blind clinical studies of male and female patients with moderate to severe Paget’s disease (alkaline phosphatase at least twice the upper limit of normal): a placebo-controlled, multinational study and a U.S. comparative study with etidronate disodium 400 mg/day. Figure 6 shows the mean percent changes from baseline in serum alkaline phosphatase for up to six months of randomized treatment.Figure 6:

Figure 6
(click image for full-size original)

At six months the suppression in alkaline phosphatase in patients treated with alendronate sodium was significantly greater than that achieved with etidronate and contrasted with the complete lack of response in placebo-treated patients. Response (defined as either normalization of serum alkaline phosphatase or decrease from baseline greater than or equal to 60%) occurred in approximately 85% of patients treated with alendronate sodium in the combined studies vs. 30% in the etidronate group and 0% in the placebo group. Alendronate sodium was similarly effective regardless of age, gender, race, prior use of other bisphosphonates, or baseline alkaline phosphatase within the range studied (at least twice the upper limit of normal).
Bone histology was evaluated in 33 patients with Paget’s disease treated with alendronate 40 mg/day for 6 months. As in patients treated for osteoporosis [see Clinical Studies (14.1)], alendronate sodium did not impair mineralization, and the expected decrease in the rate of bone turnover was observed. Normal lamellar bone was produced during treatment with alendronate sodium, even where preexisting bone was woven and disorganized. Overall, bone histology data support the conclusion that bone formed during treatment with alendronate sodium is of normal quality.

16 HOW SUPPLIED/STORAGE AND HANDLING

How Supplied

Alendronate Sodium Tablets USP, 10 mg are white to off-white, circular, biconvex, uncoated tablets debossed with ‘F’ on one side and ‘18’ on the other side.
Bottles of 30 NDC 65862-327-30
Bottles of 100 NDC 65862-327-01
Bottles of 1,000 NDC 65862-327-99
10 x 10 Unit-dose Tablets NDC 65862-327-10

Alendronate Sodium Tablets USP, 35 mg are white to off-white, oval shaped, biconvex, uncoated tablets debossed with ‘F’ on one side and ‘19’ on the other side.
Unit-of-use blister package of 4 NDC 65862-328-04
Unit-of-use blister package of 12 NDC 65862-328-08
Unit-of-use blister package of 20 NDC 65862-328-20
10 x 10 Unit-dose Tablets NDC 65862-328-10

Alendronate Sodium Tablets USP, 70 mg are white to off-white, oval shaped, biconvex, uncoated tablets debossed with ‘F’ on one side and ‘21’ on the other side.

Bottles of 100 NDC 65862-329-01
Bottles of 500 NDC 65862-329-05
Unit-of-use blister package of 4 NDC 65862-329-04
Unit-of-use blister package of 12 NDC 65862-329-08
Unit-of-use blister package of 20 NDC 65862-329-20
10 x 10 Unit-dose Tablets NDC 65862-329-10

Storage

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Store in a well-closed container.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide). Instruct patients to read the Medication Guide before starting therapy with alendronate sodium and to reread it each time the prescription is renewed.

17.1 Osteoporosis Recommendations, Including Calcium and Vitamin D Supplementation

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

17.2 Dosing Instructions

Instruct patients that the expected benefits of alendronate sodium may only be obtained when it is taken with plain water the first thing upon arising for the day at least 30 minutes before the first food, beverage, or medication of the day. Even dosing with orange juice or coffee has been shown to markedly reduce the absorption of alendronate sodium [see Clinical Pharmacology (12.3)].
Instruct patients not to chew or suck on the tablet because of a potential for oropharyngeal ulceration.
Instruct patients to swallow each tablet of alendronate sodium with a full glass of 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 at least 30 minutes and until after their first food of the day.
Instruct patients not to take alendronate sodium at bedtime or before arising for the day. Patients should be informed that failure to follow these instructions may increase their risk of esophageal problems.
Instruct patients that if they develop symptoms of esophageal disease (such as difficulty or pain upon swallowing, retrosternal pain or new or worsening heartburn) they should stop taking alendronate sodium and consult their physician.
If patients miss a dose of once weekly alendronate sodium, instruct patients to take one dose on the morning after they remember. They should not take two doses on the same day but should return to taking one dose once a week, as originally scheduled on their chosen day.
Dispense with Medication Guide available at: www.aurobindousa.com/medication-guides

Distributed by:
Aurobindo Pharma USA, Inc.
279 Princeton-Hightstown Road
East Windsor, NJ 08520
Manufactured by:
Aurobindo Pharma Limited
Hyderabad–500 032, India
Revised: 01/2024

Dispense with Medication Guide available at: www.aurobindousa.com/medication-guides

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