1.1 Postmenopausal Osteoporosis

Risedronate sodium tablets, USP are indicated for the treatment and prevention of osteoporosis in postmenopausal women. In postmenopausal women with osteoporosis, risedronate reduces the incidence of vertebral fractures and a composite endpoint of nonvertebral osteoporosis-related fractures [see Clinical Studies (14.1, 14.2)].

1.5 Important Limitations of Use

The optimal duration of use has not been determined. The safety and effectiveness of risedronate sodium tablets for the treatment of osteoporosis are based on clinical data of 3 years duration. All patients on bisphosphonate therapy should have the need for continued therapy re-eva luated on a periodic basis. Patients at low-risk for fracture should be considered for drug discontinuation after 3 to 5 years of use. Patients who discontinue therapy should have their risk for fracture re-eva luated periodically.

2.1 Treatment of Postmenopausal Osteoporosis

[See Indications and Usage (1.1).]

The recommended regimen is:

•

one 75 mg tablet orally, taken on two consecutive days for a total of two tablets each month or

•

one 150 mg tablet orally, taken once-a-month

2.2 Prevention of Postmenopausal Osteoporosis

[See Indications and Usage (1.1).]

The recommended regimen is:

•

one 75 mg tablet orally, taken on two consecutive days for a total of two tablets each month may be considered or

•

one 150 mg tablet orally, taken once-a-month may be considered

2.6 Important Administration Instructions

Instruct patients to do the following:

•

Take risedronate sodium tablets at least 30 minutes before the first food or drink of the day other than water, and before taking any oral medication or supplementation, including calcium, antacids, or vitamins to maximize absorption and clinical benefit, [ see Drug Interactions (7.1)]. Avoid the use of water with supplements, including mineral water, because they may have a higher concentration of calcium.

•

Swallow risedronate sodium tablets whole with a full glass of plain water (6 to 8 ounces). Avoid lying down for 30 minutes after taking the medication [ see Warnings and Precautions (5.1)]. Do not chew or suck the tablet because of a potential for oropharyngeal ulceration.

•

Do not eat or drink anything except plain water, or take other medications for at least 30 minutes after taking risedronate sodium tablets.

2.7 Recommendations for Calcium and Vitamin D Supplementation

Instruct patients to take supplemental calcium and vitamin D if their dietary intake is inadequate; and to take calcium supplements, antacids, magnesium-based supplements or laxatives, and iron preparations at a different time of the day as they interfere with the absorption of risedronate sodium tablets.

2.8 Administration Instructions for Missed Doses

Instruct patients about missing risedronate sodium tablet doses as follows:

•

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 more than 7 days away:

•

If both tablets are missed, take one risedronate sodium 75 mg tablet in the morning after the day it is remembered and then the other tablet on the next consecutive morning.

•

If only one risedronate sodium 75 mg tablet is missed, take the missed tablet in the morning after the day it is remembered.

•

Return to taking their risedronate sodium 75 mg tablets on two consecutive days per month as originally scheduled.

•

Do 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:

•

Wait until their next month’s scheduled doses and then continue taking risedronate sodium 75 mg tablets on two consecutive days per month as originally scheduled.

•

If the dose of risedronate sodium 150 mg once-a-month is missed, and the next month’s scheduled dose is more than 7 days away:

•

Take the missed tablet in the morning after the day it is remembered and then return to taking their risedronate sodium 150 mg tablet once-a-month as originally scheduled.

•

Do not take more than one 150 mg tablet within 7 days.

•

If the dose of risedronate sodium 150 mg once-a-month is missed, and the next month's scheduled dose is within 7 days:

•

Wait until their next month’s scheduled dose and then continue taking risedronate sodium 150 mg tablet once-a-month as originally scheduled.

5.1 Drug Products with the Same Active Ingredient

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

5.2 Upper Gastrointestinal Adverse Reactions

Risedronate, 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 is 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 (17.1)].

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 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 full glass (6 to 8 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 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.

5.3 Mineral Metabolism

Hypocalcemia has been reported in patients taking risedronate. Treat hypocalcemia and other disturbances of bone and mineral metabolism before starting risedronate 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, especially in patients with Paget’s disease in whom bone turnover is significantly elevated [see Contraindications (4), Adverse Reactions (6.1), Information for Patients (17.1)].

5.4 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 pre-existing 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 osteonecrosis of the jaw 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)].

5.5 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.

5.6 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 eva luated 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.

5.7 Renal Impairment

Risedronate is not recommended for use in patients with severe renal impairment (creatinine clearance less than 30 mL/min).

5.8 Glucocorticoid-Induced Osteoporosis

Before initiating risedronate treatment for the treatment and prevention of glucocorticoid-induced osteoporosis, the sex steroid hormonal status of both men and women should be ascertained and appropriate replacement considered.

5.9 Laboratory Test Interactions

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