Alendronate Sodium: Package Insert and Label Information (Page 4 of 5)

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 40-60 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

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 Dosing

The 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 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 also reduced height loss (alendronate, -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, 2.0%; 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:

Studies in Glucocorticoid – Treated Patients

Increase in BMD

Alendronate 5mg/day at One Year

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 was effective regardless of dose or duration of glucocorticoid use. In addition, alendronate 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 5.0% 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: Studies in Paget’s Disease of Bone

At six months the suppression in alkaline phosphatase in patients treated with alendronate 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 in the combined studies vs. 30% in the etidronate group and 0% in the placebo group. Alendronate 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 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, even where preexisting bone was woven and disorganized. Overall, bone histology data support the conclusion that bone formed during treatment with alendronate is of normal quality.

16 HOW SUPPLIED/STORAGE AND HANDLING

Alendronate Sodium Oral Solution, 70 mg/75 mL is supplied as a clear, colorless to pale pink solution with a raspberry flavor, free from visible particulate matter.

NDC 70954-264-10 unit-of-use cartons of 4 single-dose bottles containing 75 mL each.

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Do not freeze.

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 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 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 [see Clinical Pharmacology (12.3)].

Instruct patients to drink at least 2 ounces (a quarter of a cup) of water after taking alendronate oral solution, to facilitate gastric emptying.

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 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 and consult their physician.

If patients miss a dose of once weekly alendronate, 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.

Trademarks are the property of their respective owners.

Manufactured by:

Novitium Pharma LLC

70 Lake Drive, East Windsor

New Jersey 08520

Issued: 10/2022

LB4226-01

MEDICATION GUIDE

ONCE WEEKLY

Alendronate Sodium Oral Solution

(a len’ droe nate soe’ dee um)

Rx only

Read the Medication Guide that comes with Alendronate Sodium Oral Solution before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking with your doctor about your medical condition or treatment. Talk to your doctor if you have any questions about Alendronate Sodium Oral Solution.

What is the most important information I should know about Alendronate Sodium Oral Solution?

Alendronate Sodium Oral Solution can cause serious side effects including:

1. Esophagus problems
2. Low calcium levels in your blood (hypocalcemia)
3. Bone, joint, or muscle pain
4. Severe jaw bone problems (osteonecrosis)
5. Unusual thigh bone fractures

Esophagus problems.

Some people who take Alendronate Sodium Oral Solution may develop problems in the esophagus (the tube that connects the mouth and the stomach). These problems include irritation, inflammation, or ulcers of the esophagus which may sometimes bleed.

• It is important that you take Alendronate Sodium Oral Solution exactly as prescribed to help lower your chance of getting esophagus problems. (See the section “How should I take once weekly Alendronate Sodium Oral Solution sodium oral solution?”)
• Stop taking Alendronate Sodium Oral Solution and call your doctor right away if you get chest pain, new or worsening heartburn, or have trouble or pain when you swallow.

Low calcium levels in your blood (hypocalcemia).

Alendronate Sodium Oral Solution may lower the calcium levels in your blood. If you have low blood calcium before you start taking Alendronate Sodium Oral Solution, it may get worse during treatment. Your low blood calcium must be treated before you take Alendronate Sodium Oral Solution. Most people with low blood calcium levels do not have symptoms, but some people may have symptoms. Call your doctor right away if you have symptoms of low blood calcium such as:

• Spasms, twitches, or cramps in your muscles
• Numbness or tingling in your fingers, toes, or around your mouth

Your doctor may prescribe calcium and vitamin D to help prevent low calcium levels in your blood, while you take alendronate. Take calcium and vitamin D as your doctor tells you to.

Bone, joint, or muscle pain.

Some people who take Alendronate Sodium Oral Solution develop severe bone, joint, or muscle pain.

Severe jaw bone problems (osteonecrosis).

Severe jaw bone problems may happen when you take Alendronate Sodium Oral Solution. Your doctor should examine your mouth before you start Alendronate Sodium Oral Solution. Your doctor may tell you to see your dentist before you start Alendronate Sodium Oral Solution. It is important for you to practice good mouth care during treatment with Alendronate Sodium Oral Solution.

Unusual thigh bone fractures.

Some people have developed unusual fractures in their thigh bone. Symptoms of a fracture may include new or unusual pain in your hip, groin, or thigh.

Call your doctor right away if you have any of these side effects.

What is Alendronate Sodium Oral Solution?

Alendronate Sodium Oral Solution is a prescription medicine used to:

• Treat osteoporosis in women after menopause. It helps reduce the chance of having a hip or spinal fracture (break).
• Increase bone mass in men with osteoporosis.

It is not known how long alendronate works for the treatment and prevention of osteoporosis. You should see your doctor regularly to determine if Alendronate Sodium Oral Solution is still right for you.

Alendronate Sodium Oral Solution is not for use in children.

Who should not take Alendronate Sodium Oral Solution?

Do not take Alendronate Sodium Oral Solution if you:

• Have certain problems with your esophagus, the tube that connects your mouth with your stomach
• Cannot stand or sit upright for at least 30 minutes
• Have low levels of calcium in your blood
• Are allergic to Alendronate Sodium Oral Solution or any of its ingredients. A list of ingredients is at the end of this leaflet.

What should I tell my doctor before taking Alendronate Sodium Oral Solution?

Before you start Alendronate Sodium Oral Solution, be sure to talk to your doctor if you:

• Have problems with swallowing
• Have stomach or digestive problems
• Have low blood calcium
• Plan to have dental surgery or teeth removed
• Have kidney problems
• Have been told you have trouble absorbing minerals in your stomach or intestines (malabsorption syndrome)
• Are pregnant, trying to become pregnant or suspect that you are pregnant. If you become pregnant while taking Alendronate Sodium Oral Solution, stop taking it and contact your doctor. It is not known if Alendronate Sodium Oral Solution can harm your unborn baby.
• Are breast-feeding or plan to breast-feed. It is not known if Alendronate Sodium Oral Solution passes into your milk and may harm your baby.

Especially tell your doctor if you take:

• antacids
• aspirin
• Nonsteroidal Anti-Inflammatory (NSAID) medicines

Tell your doctor about all the medicines you take , including prescription and non-prescription medicines, vitamins, and herbal supplements. Certain medicines may affect how Alendronate Sodium Oral Solution works.

Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist each time you get a new medicine.

How should I take once weekly Alendronate Sodium Oral Solution?

• Take Alendronate Sodium Oral Solution exactly as your doctor tells you.
• Alendronate Sodium Oral Solution works only if taken on an empty stomach.
• Take Alendronate Sodium Oral Solution after you get up for the day and before taking your first food, drink, or other medicine.
• Take Alendronate Sodium Oral Solution while you are sitting or standing.
• Do not take Alendronate Sodium Oral Solution with mineral water, coffee, tea, soda, or juice.
• Choose the day of the week that best fits your schedule.
• Take 1 dose of Alendronate Sodium Oral Solution every week on your chosen day after you get up for the day and before taking your first food, drink, or other medicine.

Do not lie down for at least 30 minutes after you take Alendronate Sodium Oral Solution and after you eat your first food of the day.

If you miss a dose of Alendronate Sodium Oral Solution, do not take it later in the day. Take your missed dose on the next morning after you remember and then return to your normal schedule. Do not take 2 doses on the same day.

If you take too much Alendronate Sodium Oral Solution, call your doctor. Do not try to vomit. Do not lie down.

What are the possible side effects of Alendronate Sodium Oral Solution?

Alendronate Sodium Oral Solution may cause serious side effects.

• See “What is the most important information I should know about Alendronate Sodium Oral Solution?”

The most common side effects of Alendronate Sodium Oral Solution are:

• Stomach area (abdominal) pain
• Heartburn
• Constipation
• Diarrhea
• Upset stomach
• Pain in your bones, joints, or muscles
• Nausea

You may get allergic reactions, such as hives or swelling of your face, lips, tongue, or throat.

Worsening of asthma has been reported.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Alendronate Sodium Oral Solution. For more information, ask your doctor or pharmacist.

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

How do I store Alendronate Sodium Oral Solution?

• Store Alendronate Sodium Oral Solution at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Do not freeze.
• Keep Alendronate Sodium Oral Solution in a tightly closed container.

Keep Alendronate Sodium Oral Solution and all medicines out of the reach of children.

General information about the safe and effective use of Alendronate Sodium Oral Solution.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Alendronate Sodium Oral Solution for a condition for which it was not prescribed. Do not give Alendronate Sodium Oral Solution to other people, even if they have the same symptoms you have. It may harm them.

This Medication Guide summarizes the most important information about Alendronate Sodium Oral Solution. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Alendronate Sodium Oral Solution that is written for health professionals.

What are the ingredients in Alendronate Sodium Oral Solution?

Active ingredient: alendronate sodium

Inactive ingredients: citric acid (anhydrous), methylparaben, propylparaben, purified water, raspberry flavor, saccharin sodium and sodium citrate dihydrate.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Trademarks are the property of their respective owners.

Manufactured by:

Novitium Pharma LLC

70 Lake Drive, East Windsor

New Jersey 08520

Issued: 10/2022

LB4226-01