Risedronate Sodium

• Treatment and prevention of postmenopausal osteoporosis (
  1.1 Postmenopausal Osteoporosis

  Risedronate sodium tablets are indicated for the treatment and prevention of osteoporosis in postmenopausal women. In postmenopausal women with osteoporosis, risedronate sodium tablets reduce the incidence of vertebral fractures and a composite endpoint of nonvertebral osteoporosis-related fractures [

  see Clinical Studies

  ].
  )
• Treatment to increase bone mass in men with osteoporosis (
  1.2 Osteoporosis in Men

  Risedronate sodium tablets are indicated for treatment to increase bone mass in men with osteoporosis.
  )
• Treatment and prevention of glucocorticoid-induced osteoporosis (
  1.3 Glucocorticoid-Induced Osteoporosis

  Risedronate sodium tablets are indicated for the treatment and prevention of glucocorticoid-induced osteoporosis in men and women who are either initiating or continuing systemic glucocorticoid treatment (daily dosage of greater than or equal to 7.5 mg of prednisone or equivalent) for chronic diseases. Patients treated with glucocorticoids should receive adequate amounts of calcium and vitamin D.
  )
• Treatment of Paget's disease (
  1.4 Paget's Disease

  Risedronate sodium tablets are indicated for treatment of Paget's disease of bone in men and women.
  )

Optimal duration of use has not been determined. For patients at low-risk for fracture, consider drug discontinuation after 3 to 5 years of use. (

Prevention of Postmenopausal Osteoporosis: 5 mg daily, 35 mg once-a-week (

Men with Osteoporosis: 35 mg once-a-week (

Glucocorticoid-Induced Osteoporosis: 5 mg daily (

Paget's Disease: 30 mg daily for 2 months (

Instruct patients to:

• Swallow tablet whole with 6 to 8 ounces of plain water, at least 30 minutes before the first food, beverage, or medication of the day
• Avoid lying down for 30 minutes (
  2 DOSAGE AND ADMINISTRATION

  Treatment of Postmenopausal Osteoporosis: 5 mg daily, 35 mg once-a-week, 75 mg two consecutive days each month, 150 mg once-a-month (

  2.1

  )

  Prevention of Postmenopausal Osteoporosis: 5 mg daily, 35 mg once-a-week

  Men with Osteoporosis: 35 mg once-a-week

  Glucocorticoid-Induced Osteoporosis: 5 mg daily

  Paget's Disease: 30 mg daily for 2 months

  
  
  Instruct patients to:

  • Swallow tablet whole with 6 to 8 ounces of plain water, at least 30 minutes before the first food, beverage, or medication of the day
  • Avoid lying down for 30 minutes
  • Take supplemental calcium and vitamin D if dietary intake is inadequate

  2.1 Treatment of Postmenopausal Osteoporosis

  [see Indications and Usage (1.1)]

  The recommended regimen is:

  • one 5 mg tablet orally, taken daily or
  • one 35 mg tablet orally, taken once-a-week or
  • 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 5 mg tablet orally, taken daily or
  • one 35 mg tablet orally, taken once-a-week or
  • alternatively, one 75 mg tablet orally, taken on two consecutive days for a total of two tablets each month may be considered or
  • alternatively, one 150 mg tablet orally, taken once-a-month may be considered

  2.3 Treatment to Increase Bone Mass in Men with Osteoporosis

  [see Indications and Usage (1.2)]

  The recommended regimen is:

  • one 35 mg tablet orally, taken once-a-week

  2.4 Treatment and Prevention of Glucocorticoid-Induced Osteoporosis

  [see Indications and Usage (1.3)]

  The recommended regimen is:

  • one 5 mg tablet orally, taken daily

  2.5 Treatment of Paget's Disease

  [see Indications and Usage (1.4)]

  The recommended treatment regimen is 30 mg orally once daily for 2 months. Retreatment may be considered (following post-treatment observation of at least 2 months) if relapse occurs, or if treatment fails to normalize serum alkaline phosphatase. For retreatment, the dose and duration of therapy are the same as for initial treatment. No data are available on more than 1 course of retreatment.

  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.

  2.8 Administration Instructions for Missed Doses

  Instruct patients about missing risedronate sodium tablets doses as follows:

  • If a dose of risedronate sodium tablets 35 mg once-a-week is missed:
    • 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.
    • Do not take 2 tablets on the same day.

  • 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 tablet 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 tablets 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:
    • Take the missed tablet in the morning after the day it is remembered and then return to taking their risedronate sodium tablet 150 mg once-a-month as originally scheduled.
    • Do 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:
    • Wait until their next month’s scheduled dose and then continue taking risedronate sodium tablet 150 mg once-a-month as originally scheduled.
  )
• Take supplemental calcium and vitamin D if dietary intake is inadequate (
  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.
  )

• 5 mg film-coated, round, yellow tablets debossed ‘5’ on one side and ‘S’ on other side.
• 30 mg film-coated, round, white tablets debossed ‘667’ on one side and ‘S’ on other side.
• 35 mg film-coated, round, brown tablets debossed ‘668’ on one side and ‘S’ on other side.
• 75 mg film-coated, round, pink tablets debossed ‘727’ on one side and ‘S’ on other side.
• 150 mg film-coated, round, blue tablets debossed ‘928’ on one side and ‘S’ on other side.

• Pregnancy: Discontinue when pregnancy is recognized (8.1) 
• Risedronate sodium is not recommended for use in patients with severe renal impairment (creatinine clearance less than 30 mL/min) (5.6, 8.6, 12.3)
• Risedronate sodium is not indicated for use in pediatric patients (8.4)

• Products Containing Same Active Ingredient:
  Patients receiving risedronate sodium delayed-release tablets should not be treated with risedronate sodium tablets(
  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.
  )
• Upper Gastrointestinal Adverse Reactions
  can occur. Instruct patients to follow dosing instructions. Discontinue use if new or worsening symptoms occur (
  5.2 Upper Gastrointestinal Adverse Reactions

  Risedronate sodium, 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 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 , Adverse Reactions , Information for Patients

  ].

  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 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

  ]. In patients who cannot comply with dosing instructions due to mental disability, therapy with risedronate sodium 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.
  )
• Hypocalcemia
  may worsen and must be corrected prior to use (
  5.3 Mineral Metabolism

  Hypocalcemia has been reported in patients taking risedronate sodium tablets. Treat hypocalcemia and other disturbances of bone and mineral metabolism before starting risedronate sodium tablet 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 , Adverse Reactions , Information for Patients

  ].
  )
• Osteonecrosis of the Jaw
  has been reported (
  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 sodium. 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 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)].
  )
• Severe Bone, Joint, Muscle Pain
  may occur. Discontinue use if severe symptoms develop (
  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

  ]. 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.
  ,
  6.2 Postmarketing Experience

  Because these adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

  Hypersensitivity Reactions

  Hypersensitivity and skin reactions have been reported, including angioedema, generalized rash, bullous skin reactions, Stevens-Johnson syndrome and toxic epidermal necrolysis.

  Gastrointestinal Adverse Events

  Events involving upper gastrointestinal irritation, such as esophagitis and esophageal or gastric ulcers, have been reported [

  see Warnings and Precautions (5.1)

  ].

  Musculoskeletal Pain

  Bone, joint, or muscle pain, described as severe or incapacitating, have been reported rarely [

  see Warnings and Precautions (5.4)

  ].

  Eye Inflammation

  Reactions of eye inflammation including iritis and uveitis have been reported rarely.

  Jaw Osteonecrosis

  Osteonecrosis of the jaw has been reported rarely [

  see Warnings and Precautions (5.3)

  ].

  Pulmonary

  Asthma exacerbations
  )
• Atypical Femur Fractures
  have been reported. Patients with new thigh or groin pain should be evaluated to rule out a femoral fracture (
  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 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.
  )