Risedronate Delayed Release

Drug Products With the Same Active Ingredient

Risedronate sodium delayed-release tablets contain the same active ingredient found in Actonel®. A patient being treated with Actonel should not receive risedronate sodium delayed-release tablets.

Upper Gastrointestinal Adverse Reactions

Risedronate sodium delayed-release tablets, like other bisphosphonates administered orally, may cause local irritation of the upper gastrointestinal mucosa. Because of these possible irritant effects and a potential for worsening of the underlying disease, caution should be used when risedronate sodium delayed-release tablets are given to patients with active upper gastrointestinal problems (such as known Barrett’s esophagus, dysphagia, other esophageal diseases, gastritis, duodenitis or ulcers) [see Contraindications (4), Adverse Reactions (6.1), Information for Patients (17)].

Esophageal adverse experiences, such as esophagitis, esophageal ulcers and esophageal erosions, occasionally with bleeding and rarely followed by esophageal stricture or perforation, have been reported in patients receiving treatment with oral bisphosphonates. In some cases, these have been severe and required hospitalization. Physicians should therefore be alert to any signs or symptoms signaling a possible esophageal reaction and patients should be instructed to discontinue risedronate sodium delayed-release tablets and seek medical attention if they develop dysphagia, odynophagia, retrosternal pain or new or worsening heartburn.

The risk of severe esophageal adverse experiences appears to be greater in patients who lie down after taking oral bisphosphonates and/or who fail to swallow it with the recommended 4 ounces of water, and/or who continue to take oral bisphosphonates after developing symptoms suggestive of esophageal irritation. Therefore, it is very important that the full dosing instructions are provided to, and understood by, the patient [see Dosage and Administration (2)]. In patients who cannot comply with dosing instructions due to mental disability, therapy with risedronate sodium delayed-release tablets should be used under appropriate supervision.

There have been postmarketing reports of gastric and duodenal ulcers with oral bisphosphonate use, some severe and with complications, although no increased risk was observed in controlled clinical trials.

Mineral Metabolism

Hypocalcemia has been reported in patients taking risedronate sodium delayed-release tablets. Treat hypocalcemia and other disturbances of bone and mineral metabolism should be effectively treated before starting risedronate sodium delayed-release tablets therapy. Instruct patients to take supplemental calcium and vitamin D if their dietary intake is inadequate. Adequate intake of calcium and vitamin D is important in all patients [see Contraindications (4), Adverse Reactions (6.1), Information for Patients (17)].

Jaw Osteonecrosis

Osteonecrosis of the jaw (ONJ), which can occur spontaneously, is generally associated with tooth extraction and/or local infection with delayed healing, and has been reported in patients taking bisphosphonates, including risedronate. Known risk factors for osteonecrosis of the jaw include invasive dental procedures (for example, tooth extraction, dental implants, boney surgery), diagnosis of cancer, concomitant therapies (for example, chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, and co-morbid disorders (for example, periodontal and/or other preexisting dental disease, anemia, coagulopathy, infection, ill-fitting dentures). The risk of ONJ may increase with duration of exposure to bisphosphonates.

For patients requiring invasive dental procedures, discontinuation of bisphosphonate treatment may reduce the risk for ONJ. Clinical judgment of the treating physician and/or oral surgeon should guide the management plan of each patient based on individual benefit/risk assessment.

Patients who develop ONJ while on bisphosphonate therapy should receive care by an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition. Discontinuation of bisphosphonate therapy should be considered based on individual benefit/risk assessment [see Adverse Reactions (6.2)].

Musculoskeletal Pain

In postmarketing experience, there have been reports of severe and occasionally incapacitating bone, joint, and/or muscle pain in patients taking bisphosphonates [see Adverse Reactions (6.2)]. The time to onset of symptoms varied from one day to several months after starting the drug. Most patients had relief of symptoms after stopping medication. A subset had recurrence of symptoms when rechallenged with the same drug or another bisphosphonate. Consider discontinuing use if severe symptoms develop.

Atypical Subtrochanteric and Diaphyseal Femoral Fractures

Atypical, low-energy, or low trauma fractures of the femoral shaft have been reported in bisphosphonate-treated patients. These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are traverse or short oblique in orientation without evidence of comminution. Causality has not been established as these fractures also occur in osteoporotic patients who have not been treated with bisphosphonates.

Atypical femur fractures most commonly occur with minimal or no trauma to the affected area. They may be bilateral and many patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs. A number of reports note that patients were also receiving treatment with glucocorticoids (for example, prednisone) at the time of fracture.

Any patient with a history of bisphosphonate exposure who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Patients presenting with an atypical fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of bisphosphonate therapy should be considered, pending a risk/benefit assessment, on an individual basis.

Renal Impairment

Risedronate sodium delayed-release tablets are not recommended for use in patients with severe renal impairment (creatinine clearance less than 30 mL/min) because of lack of clinical experience.

Laboratory Test Interactions

Bisphosphonates are known to interfere with the use of bone-imaging agents. Specific studies with risedronate sodium delayed-release tablets have not been performed.

Pregnancy

Teratogenic Effects

Pregnancy category C

There are no adequate and well-controlled studies of risedronate sodium delayed-release tablets in pregnant women. Risedronate sodium delayed-release tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus.

Bisphosphonates are incorporated into the bone matrix, from which they are gradually released over periods of weeks to years. The amount of bisphosphonate incorporation into adult bone, and hence, the amount available for release back into the systemic circulation, is directly related to the dose and duration of bisphosphonate use. There are no data on fetal risk in humans. However, there is a theoretical risk of fetal harm, predominantly skeletal, if a woman becomes pregnant after completing a course of bisphosphonate therapy. The impact of variables such as time between cessation of bisphosphonate therapy to conception, the particular bisphosphonate used, and the route of administration (intravenous versus oral) on this risk has not been studied.

In animal studies, pregnant rats received risedronate sodium during organogenesis at doses 1 to 26 times the human Paget’s disease dose of 30 mg/day. Survival of neonates was decreased in rats treated during gestation with oral doses approximately 5 times the human dose and body weight was decreased in neonates from dams treated with approximately 26 times the human dose. The number of fetuses exhibiting incomplete ossification of sternebrae or skull from dams treated with approximately 2.5 times the human dose was significantly increased compared to controls. Both incomplete ossification and unossified sternebrae were increased in rats treated with oral doses approximately 5 times the human dose. A low incidence of cleft palate was observed in fetuses from female rats treated with oral doses approximately equal to the human dose. The relevance of this finding to human use of risedronate sodium delayed-release tablets is unclear.

No significant fetal ossification effects were seen in rabbits treated with oral doses approximately 7 times the human dose (the highest dose tested). However, 1 of 14 litters were aborted and 1 of 14 litters were delivered prematurely.

Similar to other bisphosphonates, treatment during mating and gestation with doses of risedronate sodium approximately the same as the human Paget’s disease dose of 30 mg/day resulted in periparturient hypocalcemia and mortality in pregnant rats allowed to deliver.

Dosing multiples provided above are based on the recommended human Paget’s disease dose of 30 mg/day and normalized using body surface area (mg/m2). Actual animal doses were 3.2, 7.1 and 16 mg/kg/day in the rat and 10 mg/kg/day in the rabbit.

Nursing Mothers

Risedronate was detected in feeding pups exposed to lactating rats for a 24 hour period post-dosing, indicating a small degree of lacteal transfer. It is not known whether risedronate sodium is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from risedronate sodium delayed-release tablets, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Risedronate sodium delayed-release tablets are not indicated for use in pediatric patients.

The safety and effectiveness of risedronate sodium immediate-release was assessed in a one-year, randomized, double-blind, placebo-controlled study of 143 pediatric patients (94 received risedronate) with osteogenesis imperfecta (OI). The enrolled population was predominantly patients with mild OI (85% Type-I), aged 4 to less than 16 years, 50% male and 82% Caucasian, with a mean lumbar spine BMD Z-score of -2.08 (2.08 standard deviations below the mean for age-matched controls). Patients received either a 2.5 mg (less than or equal to 30 kg body weight) or 5 mg (greater than 30 kg body weight) daily oral dose. After one year, an increase in lumbar spine BMD in the risedronate sodium immediate-release group compared to the placebo group was observed. However, treatment with risedronate sodium immediate-release did not result in a reduction in the risk of fracture in pediatric patients with OI. In risedronate sodium immediate-release treated subjects, no mineralization defects were noted in paired bone biopsy specimens obtained at baseline and month 12.

The overall safety profile of risedronate in OI patients treated for up to 12 months was generally similar to that of adults with osteoporosis. However, there was an increased incidence of vomiting compared to placebo. In this study, vomiting was observed in 15% of children treated with risedronate sodium immediate-release and 6% of patients treated with placebo. Other adverse reactions reported in greater than or equal to 10% of patients treated with risedronate sodium immediate-release and with a higher frequency than placebo were: pain in the extremity (21% with risedronate sodium immediate-release versus 16% with placebo), headache (20% versus 8%), back pain (17% versus 10%), pain (15% versus 10%), upper abdominal pain (11% versus 8%), and bone pain (10% versus 4%).

Geriatric Use

Of the patients receiving risedronate sodium delayed-release tablets in postmenopausal osteoporosis studies, 59% were 65 and over, while 13% were 75 and over. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Renal Impairment

Risedronate sodium delayed-release tablets are not recommended for use in patients with severe renal impairment (creatinine clearance less than 30 mL/min) because of lack of clinical experience. No dosage adjustment is necessary in patients with a creatinine clearance greater than or equal to 30 mL/min.

Hepatic Impairment

No studies have been performed to assess risedronate sodium’s safety or efficacy in patients with hepatic impairment. Risedronate is not metabolized in human liver preparations. Dosage adjustment is unlikely to be needed in patients with hepatic impairment.

Decreases in serum calcium and phosphorus following substantial overdose may be expected in some patients. Signs and symptoms of hypocalcemia may also occur in some of these patients. While milk or antacids containing calcium may be given to bind risedronate sodium immediate-release and reduce absorption of the drug, the impact of this intervention for risedronate sodium delayed-release tablets has not been evaluated.

In cases of substantial overdose, gastric lavage may be considered to remove unabsorbed drug. Standard procedures that are effective for treating hypocalcemia, including the administration of calcium intravenously, would be expected to restore physiologic amounts of ionized calcium and to relieve signs and symptoms of hypocalcemia.

Lethality after single oral doses of risedronate was seen in female rats at 903 mg/kg and male rats at 1703 mg/kg. The minimum lethal dose in mice and rabbits was 4000 mg/kg and 1000 mg/kg, respectively. These values represent 320 to 620 times the human Paget’s disease dose of 30 mg/day based on surface area (mg/m2).

Risedronate sodium delayed-release tablets contain a pH-sensitive enteric coating and a chelating agent (EDTA).

Risedronate is a pyridinyl bisphosphonate that inhibits osteoclast-mediated bone resorption and modulates bone metabolism. Each risedronate sodium delayed-release tablet for oral administration contains the equivalent of 35 mg of anhydrous risedronate sodium in the form of the monohydrate. The chemical name of risedronate sodium is [1-hydroxy-2-(3-pyridinyl)ethylidene]bis[phosphonic acid] monosodium salt. The chemical structure of risedronate sodium monohydrate is the following:

C7H10NO7P2Na•H2O M.W. Monohydrate: 323.10 Anhydrous: 305.10

Risedronate sodium monohydrate is a white to off-white powder. It is soluble in water and in aqueous solutions, and essentially insoluble in common organic solvents.

Inactive Ingredients

Colloidal silicon dioxide, edetate disodium, magnesium stearate, methacrylic acid copolymer, microcrystalline cellulose, polysorbate 80, sodium starch glycolate, stearic acid, talc, and triethyl citrate.

Treatment of Osteoporosis in Postmenopausal Women

The efficacy of risedronate sodium delayed-release tablet, 35 mg once-a-week in the treatment of postmenopausal osteoporosis was demonstrated in a randomized, double-blind, active-control trial of approximately 900 subjects. All patients in this study received supplemental calcium (1000 mg/day) and vitamin D (800 to 1000 international units/day). The primary efficacy endpoint was percent change in lumbar spine bone mineral density at 1 year.

Risedronate sodium delayed-release tablet, 35 mg once-a-week administered after breakfast was shown to be non-inferior to risedronate sodium immediate-release 5 mg daily. Table 2 presents the primary efficacy analysis, percent change in lumbar spine BMD, in the intent-to-treat population with last observation carried forward (LOCF).

Table 2: Lumbar Spine BMD - Percent Change From Baseline at Endpoint*

* at 1 year LOCF † LS Mean Difference is 5 mg daily minus 35 mg weekly treatment. ‡ Indicates a statistically significant difference from baseline determined from 95% CI unadjusted for multiple comparisons.
	Risedronate sodium immediate-release 5 mg Daily N = 307	Risedronate sodium delayed-release Tablet, 35 mg Once-a-Week Following Breakfast N = 307
Primary Efficacy (LOCF) n LS Mean (95% CI) LS Mean Difference† (95% CI)	270 3.1‡ (2.7, 3.5)	261 3.3‡ (2.9, 3.7) -0.2 (-0.8, 0.3)
N = number of intent-to-treat patients within specified treatment; n = number of patients with values at the visit. LS = Least Squares

Fracture efficacy with risedronate sodium immediate-release 5 mg daily

The fracture efficacy of risedronate sodium immediate-release 5 mg daily in the treatment of postmenopausal osteoporosis was demonstrated in 2 large, randomized, placebo-controlled, double-blind studies that enrolled a total of almost 4000 postmenopausal women under similar protocols. The Multinational study (VERT MN) (risedronate sodium immediate-release 5 mg daily, N = 408) was conducted primarily in Europe and Australia; a second study was conducted in North America (VERT NA) (risedronate sodium immediate-release 5 mg daily, N = 821). Patients were selected on the basis of radiographic evidence of previous vertebral fracture, and therefore, had established disease. The average number of prevalent vertebral fractures per patient at study entry was 4 in VERT MN, and 2.5 in VERT NA, with a broad range of baseline BMD levels. All patients in these studies received supplemental calcium 1000 mg/day. Patients with low 25-hydroxyvitamin D3 levels (approximately 40 nmol/L or less) also received 500 international units/day supplemental vitamin D.

Effect on Vertebral Fractures

Fractures of previously undeformed vertebrae (new fractures) and worsening of preexisting vertebral fractures were diagnosed radiographically; some of these fractures were also associated with symptoms (that is, clinical fractures). Spinal radiographs were scheduled annually and prospectively planned analyses were based on the time to a patient’s first diagnosed fracture. The primary endpoint for these studies was the incidence of new and worsening vertebral fractures across the period of 0 to 3 years. Risedronate sodium immediate-release 5 mg daily significantly reduced the incidence of new and worsening vertebral fractures and of new vertebral fractures in both VERT NA and VERT MN at all time points (Table 3). The reduction in risk seen in the subgroup of patients who had 2 or more vertebral fractures at study entry was similar to that seen in the overall study population.

Table 3: The Effect of Risedronate Sodium 5 mg Immediate-Release Daily on the Risk of Vertebral Fractures

* Calculated by Kaplan-Meier methodology.
VERT NA	Proportion of Patients with Fracture (%)*
	Placebo N = 678	Risedronate sodium 5 mg N = 696	Absolute Risk Reduction (%)	Relative Risk Reduction (%)
New and Worsening 0 to 1 Year 0 to 2 Years 0 to 3 Years	7.2 12.8 18.5	3.9 8.0 13.9	3.3 4.8 4.6	49 42 33
New 0 to 1 Year 0 to 2 Years 0 to 3 Years	6.4 11.7 16.3	2.4 5.8 11.3	4.0 5.9 5.0	65 55 41
VERT MN	Placebo N = 346	Risedronate sodium 5 mg N = 344	Absolute Risk Reduction (%)	Relative Risk Reduction (%)
New and Worsening 0 to 1 Year 0 to 2 Years 0 to 3 Years	15.3 28.3 34.0	8.2 13.9 21.8	7.1 14.4 12.2	50 56 46
New 0 to 1 Year 0 to 2 Years 0 to 3 Years	13.3 24.7 29.0	5.6 11.6 18.1	7.7 13.1 10.9	61 59 49

Effect on Osteoporosis-Related Nonvertebral Fractures

In VERT MN and VERT NA, a prospectively planned efficacy endpoint was defined consisting of all radiographically confirmed fractures of skeletal sites accepted as associated with osteoporosis. Fractures at these sites were collectively referred to as osteoporosis-related nonvertebral fractures. Risedronate sodium immediate-release 5 mg daily significantly reduced the incidence of nonvertebral osteoporosis-related fractures over 3 years in VERT NA (8% versus 5%; relative risk reduction 39%) and reduced the fracture incidence in VERT MN from 16% to 11%. There was a significant reduction from 11% to 7% when the studies were combined, with a corresponding 36% reduction in relative risk. Figure 1 shows the overall results as well as the results at the individual skeletal sites for the combined studies.

Figure 1: Nonvertebral Osteoporosis-Related Fractures Cumulative Incidence Over 3 Years Combined VERT MN and VERT NA

Histology/Histomorphometry

Bone biopsies from 110 postmenopausal women were obtained at endpoint in the VERT NA study. Patients had received placebo or daily risedronate sodium immediate-release (2.5 mg or 5 mg) for 2 to 3 years. Histologic evaluation (N = 103) showed no osteomalacia, impaired bone mineralization, or other adverse effects on bone in risedronate sodium immediate-release treated women. These findings demonstrate that bone formed during risedronate sodium immediate-release administration is of normal quality. The histomorphometric parameter mineralizing surface, an index of bone turnover, was assessed based upon baseline and post-treatment biopsy samples from 21 treated with placebo and 23 patients treated with risedronate sodium immediate-release 5 mg daily. Mineralizing surface decreased moderately in risedronate sodium immediate-release treated patients (median percent change: placebo, -21%; risedronate sodium immediate-release 5 mg daily, -74%), consistent with the known effects of treatment on bone turnover.

Effect on Height

In the two 3 year osteoporosis treatment studies, standing height was measured yearly by stadiometer. Both risedronate sodium immediate-release 5 mg daily and placebo-treated groups lost height during the studies. Patients who received risedronate sodium immediate-release 5 mg daily had a statistically significantly smaller loss of height than those who received placebo. In VERT MN, the median annual height change was -2.4 mm/yr in the placebo group compared to -1.3 mm/yr in the risedronate sodium immediate-release 5 mg daily group. In VERT NA, the median annual height change was -1.1 mm/yr in the placebo group compared to -0.7 mm/yr in the risedronate sodium immediate-release 5 mg daily group.

Effect on Bone Mineral Density

The results of 4 randomized, placebo-controlled trials in women with postmenopausal osteoporosis (VERT MN, VERT NA, BMD MN, BMD NA) demonstrate that risedronate sodium immediate-release 5 mg daily increases BMD at the spine, hip, and wrist compared to the effects seen with placebo. Table 4 displays the significant increases in BMD seen at the lumbar spine, femoral neck, femoral trochanter, and midshaft radius in these trials compared to placebo. In both VERT studies (VERT MN and VERT NA), risedronate sodium immediate-release 5 mg daily produced increases in lumbar spine BMD that were progressive over the 3 years of treatment, and were statistically significant relative to baseline and to placebo at 6 months and at all later time points.

Table 4: Mean Percent Increase in BMD From Baseline in Patients Taking Risedronate Sodium Immediate-Release 5 mg or Placebo at Endpoint*

* The endpoint value is the value at the study's last time point for all patients who had BMD measured at that time; otherwise the last post-baseline BMD value prior to the study's last time point is used. † The duration of the studies was 3 years. ‡ The duration of the studies was 1.5 to 2 years. § BMD of the midshaft radius was measured in a subset of centers in VERT MN (placebo, N = 222; 5 mg, N = 214) and VERT NA (placebo, N = 310; 5 mg, N = 306).
	VERT MN†		VERT NA†		BMD MN‡		BMD NA‡
	Placebo N = 323	5 mg N = 323	Placebo N = 599	5 mg N = 606	Placebo N = 161	5 mg N = 148	Placebo N = 191	5 mg N = 193
Lumbar Spine Femoral Neck Femoral Trochanter Midshaft Radius	1.0 -1.4 -1.9 -1.5§	6.6 1.6 3.9 0.2§	0.8 -1.0 -0.5 -1.2§	5.0 1.4 3.0 0.1§	0.0 4.0 -1.1 1.3 -0.6 2.5 ND		0.2 4.8 0.1 2.4 1.3 4.0 ND
ND = analysis not done

Risedronate Sodium (rih-SED-roe-nate SOE-dee-um) Delayed-Release Tablets

Read this Medication Guide that comes with risedronate sodium delayed-release tablets before you start taking them 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 your treatment. Talk to your doctor if you have any questions about risedronate sodium delayed-release tablets, there may be new information about it.

What is the most important information I should know about risedronate sodium delayed-release tablets?

Risedronate sodium delayed-release tablets can cause serious side effects including:

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

1. Esophagus problems.

Some people who take risedronate sodium delayed-release tablets 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 risedronate sodium delayed-release tablets exactly as prescribed to help lower your chance of getting esophagus problems. (See the section “How should I take risedronate sodium delayed-release tablets?”) • Stop taking risedronate sodium delayed-release tablets and call your doctor right away if you get chest pain, new or worsening heartburn, or have trouble or pain when you swallow.

2. Low calcium levels in your blood (hypocalcemia).

Risedronate sodium delayed-release tablets may lower the calcium levels in your blood. If you have low blood calcium before you start taking risedronate sodium delayed-release tablets, it may get worse during treatment. Your low blood calcium must be treated before you take risedronate sodium delayed-release tablets. 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 are taking risedronate sodium delayed-release tablets. Take calcium and vitamin D as your doctor tells you to.

3. Severe jaw bone problems (osteonecrosis).

Severe jaw bone problems may happen when you take risedronate sodium delayed-release tablets. Your doctor should examine your mouth before you start risedronate sodium delayed-release tablets. Your doctor may tell you to see your dentist before you start risedronate sodium delayed-release tablets. It is important for you to practice good mouth care during treatment with risedronate sodium delayed-release tablets.

4. Bone, joint, or muscle pain.

Some people who take risedronate sodium delayed-release tablets develop severe bone, joint, or muscle pain.

5. 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 are risedronate sodium delayed-release tablets?

Risedronate sodium delayed-release tablets are a prescription medicine used to treat osteoporosis in women after menopause.

It is not known how long risedronate sodium delayed-release tablets work for the treatment and prevention of osteoporosis. You should see your doctor regularly to determine if risedronate sodium delayed-release tablets are still right for you.

Risedronate sodium delayed-release tablets are not for use in children.

Who should not take risedronate sodium delayed-release tablets?

Do not take risedronate sodium delayed-release tablets if you:

• Have certain problems with your esophagus, the tube that connects your mouth and stomach • Cannot sit or stand up for at least 30 minutes • Have low blood calcium (hypocalcemia) • Are allergic to any of the other ingredients in risedronate sodium delayed-release tablets. See the end of this leaflet for a complete list of ingredients in risedronate sodium delayed-release tablets.

What should I tell my healthcare provider before taking risedronate sodium delayed-release tablets?

Before you take risedronate sodium delayed-release tablets, tell your healthcare provider if you:

• Have problems 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 mineral in your stomach or intestines (malabsorption syndrome) • Are pregnant or plan to become pregnant. It is not known if risedronate sodium delayed-release tablets can harm your unborn baby. • Are breastfeeding or plan to breastfeed. It is not known if risedronate sodium passes into your breast milk and may harm your baby. You and your doctor should decide if you will take risedronate sodium delayed-release tablets or breastfeed. You should not do both.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. Certain medicines may affect how risedronate sodium delayed-release tablets work.

Especially tell your doctor if you take:

• Actonel® or other medicines to treat osteoporosis • calcium supplements • antacids • laxatives • iron supplements

Ask your doctor or pharmacist for a list of these medications, if you are not sure.

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

How should I take risedronate sodium delayed-release tablets?

• Take risedronate sodium delayed-release tablets exactly as your doctor tells you. • Take risedronate sodium delayed-release tablets 1 time a week right after breakfast. Choose a day of the week to take risedronate sodium delayed-release tablets that best fits your schedule. • Take risedronate sodium delayed-release tablets with at least 4 ounces (about 1 half cup) of plain water. • Swallow risedronate sodium delayed-release tablets whole. Do not chew, cut, or crush risedronate sodium delayed-release tablets before swallowing. If you cannot swallow risedronate sodium delayed-release tablets whole, tell your doctor. You may need a different medicine.

After swallowing risedronate sodium delayed-release tablets wait at least 30 minutes:

• Before you lie down. You may sit, stand or walk, and do normal activities like reading. • Before you take other medicines, including antacids, calcium, and other supplements and vitamins.

Do not lie down for at least 30 minutes after you take risedronate sodium delayed-release tablets.

If you miss your weekly risedronate sodium delayed-release tablet dose, take risedronate sodium delayed-release tablets the morning after you remember then return to your normal schedule. Do not take 2 doses at the same time.

You should take calcium and vitamin D as directed by your doctor.

If you take too many risedronate sodium delayed-release tablets, call your doctor. Do not try to vomit. Do not lie down.

What are the possible side effects of risedronate sodium delayed-release tablets?

Risedronate sodium delayed-release tablets may cause serious side effects:

• See “What is the most important information I should know about risedronate sodium delayed-release tablets”.

The most common side effects of risedronate sodium delayed-release tablets include:

• diarrhea • flu-like symptoms • muscle pain • back and joint pain • upset stomach • stomach area (abdominal) pain

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

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 risedronate sodium delayed-release tablets. 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 should I store risedronate sodium delayed-release tablets?

• Store risedronate sodium delayed-release tablets between 68°F to 77°F (20°C to 25°C).

Keep risedronate sodium delayed-release tablets and all medicines out of the reach of children.

General information about the safe and effective use of risedronate sodium delayed-release tablets

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. Do not use risedronate sodium delayed-release tablets for a condition for which they were not prescribed. Do not give risedronate sodium delayed-release tablets to other people, even if they have the same symptoms you have. They may harm them.

This Medication Guide summarizes the most important information about risedronate sodium delayed-release tablets. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about risedronate sodium delayed-release tablets that is written for health professionals.

For more information, call 1-888-838-2872.

What are the ingredients in risedronate sodium delayed-release tablets?

Active ingredient: risedronate sodium

Inactive ingredients: Colloidal silicon dioxide, edetate disodium, magnesium stearate, methacrylic acid copolymer, microcrystalline cellulose, polysorbate 80, sodium starch glycolate, stearic acid, talc, and triethyl citrate.

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

All brand names listed are the registered trademarks of their respective owners and are not trademarks of Teva Pharmaceuticals USA, Inc.

TEVA PHARMACEUTICALS USA, INC.

North Wales, PA 19454

Rev. A 12/2014