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    Oral Bisphosphonate Bone Calcium Regulators

    DEA CLASS

    Rx

    DESCRIPTION

    Pyridinyl bisphosphonate; used for Paget's disease and for treatment and prevention of osteoporosis; more potent antiresorptive activity and decreased incidence of GI effects compared to other bisphosphonates; multiple dosage regimens available.

    COMMON BRAND NAMES

    Actonel, Atelvia

    HOW SUPPLIED

    Actonel/Risedronate/Risedronate Sodium Oral Tab: 5mg, 30mg, 35mg, 150mg
    Atelvia/Risedronate/Risedronate Sodium Oral Tab DR: 35mg

    DOSAGE & INDICATIONS

    For the treatment of Paget's disease (osteitis deformans) to induce remission in patients who have serum alkaline phosphatase concentrations at least twice the upper limit of normal, or are symptomatic, or are at risk for future complications of their disease.
    Oral dosage (30 mg tablet)
    Adults

    30 mg PO once daily for 2 months. Following 2 months of observation after completing this initial therapy, retreatment with risedronate may be considered if relapse occurs or if treatment fails to normalize serum alkaline phosphatase levels. The dose and duration of the retreatment regimen are the same as the initial therapy. No data are available for more than one course of retreatment.

    For the treatment of osteoporosis.
    Once daily regimen in postmenopausal women.
    Oral dosage (5 mg film-coated tablet; e.g., Actonel)
    Adult postmenopausal females

    5 mg PO once daily before breakfast. Supplement calcium and vitamin D if dietary intake inadequate. The optimal treatment duration has not been determined; therefore, all recipients of bisphosphonate therapy should undergo re-evaluation on a periodic basis. For those patients determined to be at low risk for fracture, consider stopping treatment after 3 to 5 years. After discontinuation of therapy, continue to periodically re-evaluate the fracture risk. Bisphosphonates are considered to be first-line therapy for the treatment of osteoporosis in postmenopausal women. In patients with at least 2 vertebral fractures or at least 1 vertebral fracture combined with a lumbar spine T-score 2 or less at baseline, risedronate decreased the risk of new fractures 65% to 74% during the first year of therapy as compared to controls (VERT-NA study). Over 3 years, the risk of vertebral and nonvertebral fractures significantly decreased by 41% and 39%, respectively, over controls. Bone mineral density also increased in patients treated with risedronate. Similar results were seen in an European and Australian study whose patients had more severe osteoporosis at baseline (VERT-MN study).

    Once weekly regimen in postmenopausal women.
    Oral dosage (35 mg weekly film-coated tablet; e.g., Actonel)
    Adult postmenopausal females

    35 mg PO once weekly before breakfast. Supplement calcium and vitamin D if dietary intake inadequate. The optimal treatment duration has not been determined; therefore, all recipients of bisphosphonate therapy should undergo re-evaluation on a periodic basis. For those patients determined to be at low risk for fracture, consider stopping treatment after 3 to 5 years. After discontinuation of therapy, continue to periodically re-evaluate the fracture risk. Bisphosphonates are considered to be first-line therapy for the treatment of osteoporosis in postmenopausal women. The BMD results obtained with the 35 mg once-weekly dosage are similar to those of the 5 mg daily dosage at all skeletal sites.

    Oral dosage (35 mg delayed-release weekly tablet; e.g., Atelvia)
    Adult postmenopausal females

    35 mg PO once weekly, taken immediately following breakfast. Supplement calcium and vitamin D if dietary intake inadequate. The optimal treatment duration has not been determined; therefore, all recipients of bisphosphonate therapy should undergo re-evaluation on a periodic basis. For those patients determined to be at low risk for fracture, consider stopping treatment after 3 to 5 years. After discontinuation of therapy, continue to periodically re-evaluate the fracture risk. Bisphosphonates are considered to be first-line therapy for the treatment of osteoporosis in postmenopausal women. In a randomized, double-blind trial, the risedronate delayed-release 35 mg once-weekly dosage was found to be non-inferior to risedronate immediate-release 5 mg daily in the effect on percent change in lumbar spine bone mineral density at 1 year.

    Weekly regimen in adult men with osteoporosis to increase bone mass.
    Oral dosage (35 mg weekly film-coated tablet; e.g., Actonel)
    Adult males

    35 mg PO once weekly before breakfast. Supplement calcium and vitamin D if dietary intake inadequate. In men with 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 -1 at the femoral neck and less than or equal to -2.5 at the lumbar spine, 35 mg once weekly for 2 years significantly increased the mean BMD at the lumbar spine, femoral neck, trochanter, and total hip as compared with placebo. The treatment difference was 4.5% at the lumbar spine, 1.1% at the femoral neck, 2.2% at the trochanter, and 1.5% at the total proximal femur. Men received calcium 1,000 mg/day and vitamin D 400 to 500 International Units/day.

    Daily regimen for adult men and women who are either initiating or continuing chronic systemic glucocorticosteroids (i.e., oral prednisone 7.5 mg/day or more, or equivalent).
    Oral dosage (5 mg film-coated tablet; e.g., Actonel)
    Adults

    5 mg PO once daily before breakfast. Supplement calcium and vitamin D if dietary intake inadequate. Efficacy beyond 1 year has not been studied. In clinical trials, risedronate has been shown to increase bone mineral density from baseline and in comparison to control at the lumbar spine femoral neck and femoral trochanter.

    Once monthly regimen for postmenopausal women.
    Oral dosage (150 mg once-monthly film-coated tablets; e.g., Actonel)
    Adult postmenopausal females

    150 mg PO once per month taken before breakfast. Supplement with calcium and vitamin D if intake is inadequate. The optimal treatment duration has not been determined; therefore, all recipients of bisphosphonate therapy should undergo re-evaluation on a periodic basis. For those patients determined to be at low risk for fracture, consider stopping treatment after 3 to 5 years. After discontinuation of therapy, continue to periodically re-evaluate the fracture risk. Bisphosphonates are considered to be first-line therapy for the treatment of osteoporosis in postmenopausal women.

    Oral dosage (75 mg film-coated tablets; e.g., Actonel)
    Adult postmenopausal females

    An alternative once-monthly regimen is one 75 mg tablet PO, taken before breakfast on 2 consecutive days for a total of 2 tablets (150 mg) each month. Supplement with calcium and vitamin D if intake is inadequate. The optimal treatment duration has not been determined; therefore, all recipients of bisphosphonate therapy should undergo re-evaluation on a periodic basis. For those patients determined to be at low risk for fracture, consider stopping treatment after 3 to 5 years. After discontinuation of therapy, continue to periodically re-evaluate the fracture risk. Bisphosphonates are considered to be first-line therapy for the treatment of osteoporosis in postmenopausal women.

    For osteoporosis prophylaxis.
    Once daily regimen in postmenopausal women.
    Oral dosage (5 mg film-coated tablet; e.g., Actonel)
    Adult postmenopausal females

    5 mg PO once daily before breakfast. Supplement with calcium and vitamin D if intake is inadequate. During clinical trials to prevent osteoporosis, bone mineral density increased at all sites in patients treated with risedronate both when compared to controls and to baseline.

    Once weekly regimen in postmenopausal women.
    Oral dosage (35 mg film-coated tablets; e.g., Actonel; OR 35 mg delayed-release tablets; e.g., Atelvia)
    Adult postmenopausal females

    35 mg PO once weekly as directed. The immediate release film-coated weekly tablets are taken before breakfast; the delayed-release weekly tablets are to be taken immediately following breakfast. Supplement with calcium and vitamin D if intake is inadequate. Once-weekly 35 mg risedronate prevented bone loss in postmenopausal women without osteoporosis in a 1-year, double-blind, placebo-controlled trial (n = 278 patients); all patients also received 1,000 mg elemental calcium and 400 International Units vitamin D daily.

    Once monthly regimen in postmenopausal women.
    Oral dosage (once-monthly 150 mg film-coated tablet; e.g., Actonel)
    Adult postmenopausal females

    150 mg PO once per month taken before breakfast. Supplement with calcium and vitamin D if intake is inadequate.

    Oral dosage (75 mg film-coated tablets; e.g., Actonel)
    Adult postmenopausal females

    An alternative once-monthly regimen is one 75 mg tablet PO, taken before breakfast on 2 consecutive days for a total of 2 tablets (150 mg) each month. Supplement with calcium and vitamin D if intake is inadequate.

    In men or women who are either initiating or continuing chronic systemic glucocorticosteroids (i.e., oral prednisone 7.5 mg/day or more, or equivalent).
    Oral dosage (5 mg film-coated tablet; e.g., Actonel)
    Adults

    5 mg PO once daily before breakfast. Supplement with calcium and vitamin D if intake is inadequate. Efficacy beyond 1 year has not been studied. In clinical trials, risedronate has been shown to increase bone mineral density from baseline and in comparison to control at the lumbar spine femoral neck and femoral trochanter.

    For the treatment of osteolytic bone metastases† in patients with multiple myeloma.
    Oral dosage (30 mg tablet)
    Adults

    In a small initial study, 11 patients with multiple myeloma were treated with risedronate 30 mg/day PO for 6 months and monitored for an additional 6 months. In this study risedronate treatment resulted in normal calcium levels, decreased bone resorption markers (pyridinoline and deoxypyridoline), and increased spinal bone mineral density.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    30 mg/day PO for Paget's disease; 5 mg/day, 35 mg/week (either immediate-release or delayed-release tablets), or 150 mg/month PO for osteoporosis.

    Elderly

    30 mg/day PO for Paget's disease; 5 mg/day, 35 mg/week (either immediate-release or delayed-release tablets), or 150 mg/month PO for osteoporosis.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    CrCl >= 30 ml/min: No dosage adjustment is needed.
    CrCl < 30 ml/min: Use is not recommended.

    ADMINISTRATION

    Oral Administration

    Immediate-release tablets (i.e., Actonel):
    Administer at least 30 minutes before the first food or drink of the day, other than plain water. The tablets should not be sucked or chewed.
    Administer to patients who are in an upright position with 6—8 oz. of plain water, patients should avoid lying down for 30 minutes after administration to lessen GI effects.
    Instruct patients to not eat for at least 30 minutes after administration. Separate administration of antacids, calcium supplements, or iron supplements from risedronate by at least 2 hours.
    Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate.
    Once daily dosage forms: If a once daily dose is missed and the patient has not eaten, then administer as soon as possible. If the patient has already eaten, wait at least 4 hours after eating before administration.
    Once weekly dosage forms: Administer on the same day of every week. If a once weekly dose is missed, administer the morning after it is remembered. The patient should return to their originally scheduled day of once-weekly administration. Do not administer two doses on the same day.
    Twice monthly dosage forms: Do not administer more than two 75 mg tablets within a 7 day period. If one of the twice monthly doses is missed, and the next month's scheduled doses are more than 7 days away, administer the dose the morning after it was remembered. If both of the twice monthly doses are missed, and the next month's scheduled doses are more than 7 days away, administer the first dose the morning after it was remembered and the second dose on the next consecutive morning. The patient should return to their originally scheduled days of twice-monthly administration. If one or both of the twice monthly doses are missed, and the next months scheduled doses are 1 to 7 days away, the missed doses should be skipped and the regular twice-monthly schedule resumed.
    Once monthly dosage forms: Do not administer more than one 150 mg tablet within a 7 day period. If the dose is missed, and the next month's scheduled dose is more than 7 days away, administer the dose the morning after it is remembered. The patient should then return to taking their dose as originally scheduled. If the next month's scheduled dose is 1 to 7 days away, the missed dose should be skipped and the regular schedule resumed.
     
    Delayed-release tablets (i.e., Atelvia):
    Administer immediately after breakfast with at least 4 ounces of plain water. Swallow tablets whole; do not chew, cut, or crush.
    Instruct patients to take this medicine while sitting or standing and to avoid lying down for at 30 minutes after taking this medicine.
    Separate administration of antacids, calcium supplements, and iron supplements from risedronate by at least 2 hours.
    If a once weekly dose is missed, administer the morning after it is remembered. The patient should return to their originally scheduled day of once-weekly administration. Do not administer two doses on the same day.

    STORAGE

    Actonel:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Atelvia:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

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

    Asthma, phosphonate hypersensitivity

    Risedronate is contraindicated in patients with a known hypersensitivity to risedronate or any component of the product; avoid use in patients with bis-phosphonate hypersensitivity. Angioedema, generalized rash, bullous skin reactions, Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported. Treatment with bisphosphonates has been associated with acute bronchospasm in patients with aspirin-sensitive asthma or phosphonate hypersensitivity.

    Hyperparathyroidism, hypocalcemia, vitamin D deficiency

    Hypocalcemia and other abnormalities of bone and mineral metabolism contraindicates therapy with risedronate. Also use cautiously in patients with preexisting hyperparathyroidism or vitamin D deficiency. Bisphosphonates, including risedronate, may exacerbate these conditions. Asymptomatic, small decreases in both serum calcium and serum phosphorus have been reported in some patients receiving risedronate. Adequate intake of calcium and vitamin D is important in all patients, especially in those with Paget's disease in whom bone turnover is significantly elevated.

    Achalasia, dysphagia, esophageal stricture, esophagitis, gastritis, gastroesophageal reflux disease (GERD), GI disease, hiatal hernia, inability to stand or sit upright

    As oral bisphosphonates are known to cause local irritation to gastric mucosa with prolonged contact, use of risedronate is contraindicated in patients with an inability to stand or sit upright for at least 30 minutes after dose administration (see Administration) and in those with delayed esophageal emptying due to achalasia, esophageal stricture, or other cause. Risedronate should be used with caution in patients with other upper GI disease. Bisphosphonates may cause or worsen symptoms of dysphagia, esophagitis, gastroesophageal reflux disease (GERD), hiatal hernia, gastritis, and esophageal and gastric ulcers. Additionally, exercise caution when administering NSAIDs and aspirin with risedronate, due to the potential for additive GI toxicity. Prescribers and health care professionals should closely monitor patients for any signs or symptoms an esophageal reaction. Advise patients to discontinue risedronate and seek medical attention if they develop dysphagia, odynophagia, or retrosternal pain. The risk of esophageal reactions increases in patients who do not follow the administration instructions. It is very important that patients understand and follow these instructions; direct observation may be required in those who cannot independently follow dosing instructions due to mental disability. In 2011, the FDA announced an ongoing review of data from published studies to evaluate whether use of oral bisphosphonate drugs is associated with an increased risk of esophageal cancer. There have been conflicting findings from studies evaluating this risk. At the time of the announcement, FDA states that the benefits of oral bisphosphonate drugs in reducing the risk of serious fractures in people with osteoporosis continue to outweigh their potential risks.

    Children

    Safe and effective use of risedronate in children has not been established. Bisphosphonates have been used successfully in children for treatment of specific disease states (i.e., hypercalcemia of malignancy, idiopathic or glucocorticoid induced osteoporosis, osteogenesis imperfecta, Paget's disease). However, extreme caution must be used to ensure appropriate use in children; excessive doses of bisphosphonates may compromise skeletal quality during growth, despite concomitant increases in bone density. In a case report, inappropriate and excessive doses of pamidronate in a child resulted in osteopetrosis (abnormally dense and misshapen bone predisposed to fracture). It may be advisable to monitor biochemical markers of skeletal turnover when bisphosphonates are used in children to help assure clinicians that skeletal resorption is not excessively suppressed.

    Pregnancy

    Risedronate is classified as FDA pregnancy risk category C. After a bisphosphonate is incorporated into bone matrix it is gradually released from the bone, over a period of weeks to years. The extent of bisphosphonate incorporation into adult bone, and hence, the amount available for release back into systemic circulation, is directly related to the total dose and duration of bisphosphonate use. Although there are no data on fetal risk in humans, bisphosphonates do cause fetal harm in animals, suggesting the uptake of bisphosphonates into fetal bone is greater than into maternal bone, and animal reproductive studies indicate risedronate, in particular, may induce fetal skeletal changes and decreases in serum calcium, as well as possibly effect fetal viability. Therefore, there is a theoretical risk of fetal harm if a woman becomes pregnant during or 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 on this risk has not been established. Because of the potential for adverse effects of bisphosphonates in the developing fetus, risedronate should only be used in pregnancy if the potential benefit justifies any possible risk to the mother and fetus. If, during gestation, the fetus is exposed to risedronate, ultrasound of the fetal skeleton should be undertaken.

    Breast-feeding

    It is not known if risedronate is excreted into human breast milk, and data on the use of risedronate during breast-feeding are not available. If risedronate is excreted into human breast milk, the amount secreted is expected to be low due to risedronate's low oral bioavailability and short elimination half-life. Once the mother has discontinued risedronate, secretion into the breast milk is still possible due to the long elimination of risedronate from the bone; however, the amount secreted into the milk should be even lower than when the mother was actively taking risedronate. The effects of risedronate on the nursing infant are not known. Due to the potential effects of bisphosphonates to the infant, until more information is available, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the benefit of the drug to the mother.

    Renal failure, renal impairment

    It is recommended that patients with renal failure or severe renal impairment with a creatinine clearance < 30 ml/min not receive risedronate. Renal excretion is substantially decreased in patients with a creatinine clearance < 30 ml/min. Patients with a creatinine clearance >= 30 ml/min do not require dosage adjustments.

    Geriatric

    Dosage adjustments of risedronate are not necessary in geriatric patients based on age alone. Controlled clinical trials of postmenopausal osteoporosis included a good proportion of elderly patients 65 to 75 years of age, as well as patients over 75 years of age. No overall differences in efficacy or safety were observed between older patients and younger adults during these trials. In the male osteoporosis trial, 28% of patients receiving risedronate were aged 65 to 75 years and 9% were over 75 years of age. The lumbar spine bone mineral density change for risedronate compared to placebo was 5.6% for subjects less than 65 years of age and 2.9% for subjects 65 years and older. No overall differences in safety were observed between elderly and younger patients in this trial. Per the manufacturer, however, greater sensitivity of some older individuals cannot be ruled out. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of medications in residents of long-term care facilities. The OBRA guidelines state that bisphosphonates must be taken according to very specific directions, including time of day, position, and timing relative to other medications and food. Patients receiving these medications should be monitored closely for GI complications (e.g., esophageal or gastric erosion). Potential adverse effects of bisphosphonates include dysphagia, esophagitis, gastritis, or esophageal and gastric ulcers, particularly when used in combination with oral corticosteroids, aspirin, or other NSAIDs.

    Anemia, chemotherapy, coagulopathy, corticosteroid therapy, dental disease, dental work, infection

    Osteonecrosis of the jaw has been reported in patients with cancer receiving treatment regimens which included bisphosphonates (most commonly pamidronate and zoledronic acid), but also occasionally in patients receiving chronic oral bisphosphonate therapy for osteoporosis, including risedronate. The risk may increase with duration of exposure to the bisphosphonate. In patients with cancer receiving intravenous bisphosphonates, many patients were also receiving chemotherapy and corticosteroids. The majority of reported cases have been associated with dental procedures, such as tooth extraction, and many of these patients had signs of local infection including osteomyelitis; however, cases have appeared spontaneously. It would be prudent for all patients including those with concomitant risk factors (e.g. anemia, cancer, chemotherapy, coagulopathy, corticosteroid therapy, dental disease, infection, poor oral hygiene) initiating bisphosphonate therapy to receive a dental examination with appropriate preventive dentistry and correction of dental complications prior to beginning treatment. Preventive measures such as these as well as continued regular follow-up with a dentist during bisphosphonate therapy are recommended by the American Academy of Oral Medicine as the best way to minimize the risk of osteonecrosis. Invasive dental procedures should be avoided, if possible, during treatment, but if they are necessary, should be performed by an experienced dentist with close patient follow-up. If osteonecrosis of the jaw does develop during bisphosphonate therapy, it should be noted that dental surgery may exacerbate the condition. For patients requiring dental work, no data are available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. Discontinuing the bisphosphonate once osteonecrosis develops is controversial as the estimated half-life of bisphosphonates in the bone is years.

    ADVERSE REACTIONS

    Severe

    prostatic hypertrophy / Delayed / 5.0-5.0
    toxic epidermal necrolysis / Delayed / 0-1.0
    Stevens-Johnson syndrome / Delayed / 0-1.0
    uveitis / Delayed / 0-0.1
    arrhythmia exacerbation / Early / Incidence not known
    atrial fibrillation / Early / Incidence not known
    esophageal ulceration / Delayed / Incidence not known
    peptic ulcer / Delayed / Incidence not known
    GI perforation / Delayed / Incidence not known
    GI bleeding / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    osteonecrosis / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    bone fractures / Delayed / Incidence not known

    Moderate

    constipation / Delayed / 2.9-12.9
    hypertension / Early / 10.5-10.5
    bone pain / Delayed / 5.3-10.0
    peripheral edema / Delayed / 7.7-8.2
    depression / Delayed / 6.8-6.8
    chest pain (unspecified) / Early / 5.0-6.6
    cataracts / Delayed / 6.5-6.5
    hypocalcemia / Delayed / 0.2-4.5
    nephrolithiasis / Delayed / 3.0-3.0
    gastritis / Delayed / 1.0-2.7
    glossitis / Early / 0.1-1.0
    hypophosphatemia / Delayed / 0.6-0.6
    iritis / Delayed / 0-0.1
    dysphagia / Delayed / Incidence not known
    esophagitis / Delayed / Incidence not known
    oral ulceration / Delayed / Incidence not known
    ocular inflammation / Early / Incidence not known
    conjunctivitis / Delayed / Incidence not known
    bullous rash / Early / Incidence not known

    Mild

    arthralgia / Delayed / 6.8-32.8
    infection / Delayed / 2.6-31.1
    back pain / Delayed / 5.9-28.0
    headache / Early / 2.6-20.0
    diarrhea / Early / 4.7-19.7
    vomiting / Early / 1.6-15.0
    nausea / Early / 3.6-13.2
    abdominal pain / Early / 2.3-12.2
    rash (unspecified) / Early / 7.9-11.5
    dyspepsia / Early / 3.9-10.8
    sinusitis / Delayed / 8.7-8.7
    influenza / Delayed / 6.2-7.2
    dizziness / Early / 2.6-7.1
    myalgia / Early / 1.0-6.7
    rhinitis / Early / 6.2-6.2
    pharyngitis / Delayed / 6.0-6.0
    asthenia / Delayed / 5.4-5.4
    insomnia / Early / 5.0-5.0
    musculoskeletal pain / Early / 1.6-2.0
    gastroesophageal reflux / Delayed / 1.0-1.6
    pyrosis (heartburn) / Early / Incidence not known
    ocular pain / Early / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Aluminum Hydroxide: (Moderate) Separating times of administration of the oral bisphosphonate from aluminum-containing medications will maximize absorption and clinical benefit. Aluminum hydroxide will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any aluminum containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any aluminum containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any aluminum containing product.
    Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Separating times of administration of the oral bisphosphonate from aluminum-containing medications will maximize absorption and clinical benefit. Aluminum hydroxide will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any aluminum containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any aluminum containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any aluminum containing product.
    Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Magnesium hydroxide will interfere with the absorption of risedronate. Do not take magnesium hydroxide within 2 hours of taking risedronate. (Moderate) Separating times of administration of the oral bisphosphonate from aluminum-containing medications will maximize absorption and clinical benefit. Aluminum hydroxide will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any aluminum containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any aluminum containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any aluminum containing product.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Magnesium hydroxide will interfere with the absorption of risedronate. Do not take magnesium hydroxide within 2 hours of taking risedronate. (Moderate) Separating times of administration of the oral bisphosphonate from aluminum-containing medications will maximize absorption and clinical benefit. Aluminum hydroxide will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any aluminum containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any aluminum containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any aluminum containing product.
    Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Separating times of administration of the oral bisphosphonate from aluminum-containing medications will maximize absorption and clinical benefit. Aluminum hydroxide will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any aluminum containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any aluminum containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any aluminum containing product.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
    Aspirin, ASA: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Aspirin, ASA; Carisoprodol: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Aspirin, ASA; Dipyridamole: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Aspirin, ASA; Omeprazole: (Major) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively. (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Aspirin, ASA; Oxycodone: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Aspirin, ASA; Pravastatin: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Beta-Carotene: (Minor) Doses in excess of 1,500 to 2,000 mcg per day of Vitamin A may lead to bone loss and will counteract the effects of risedronate therapy.
    Calcium Carbonate: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Calcium Carbonate; Magnesium Hydroxide: (Moderate) Magnesium hydroxide will interfere with the absorption of risedronate. Do not take magnesium hydroxide within 2 hours of taking risedronate. (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Calcium Carbonate; Risedronate: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Calcium Salts: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Calcium: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Calcium; Vitamin D: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Celecoxib: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Chromium: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Cimetidine: (Major) Use of H2-blockers with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets.
    Cod Liver Oil: (Minor) Doses in excess of 1,500 to 2,000 mcg per day of Vitamin A may lead to bone loss and will counteract the effects of risedronate therapy.
    Collagenase: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Cyanocobalamin, Vitamin B12: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Deferasirox: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including risedronate.
    Dexlansoprazole: (Major) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
    Diclofenac: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Diclofenac; Misoprostol: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Diflunisal: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Diphenhydramine; Ibuprofen: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Diphenhydramine; Naproxen: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Esomeprazole: (Major) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
    Esomeprazole; Naproxen: (Major) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively. (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Moderate) Separating times of administration of the oral bisphosphonate from iron-containing supplements and medications will maximize absorption and clinical benefit. Iron will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any iron containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any iron containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Moderate) Separating times of administration of the oral bisphosphonate from iron-containing supplements and medications will maximize absorption and clinical benefit. Iron will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any iron containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any iron containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Etodolac: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Famotidine: (Major) Use of H2-blockers with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets.
    Famotidine; Ibuprofen: (Major) Use of H2-blockers with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Fenoprofen: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Flurbiprofen: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Food: (Major) Any food, including milk products, will decrease the bioavailability of risedronate, and may also increase the risk of esophageal irritation from the medication. Patients should be informed to take risedronate at least 30 minutes before their first food or drink of the day, other than plain water.
    H2-blockers: (Major) Use of H2-blockers with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets.
    Hetastarch; Dextrose; Electrolytes: (Moderate) Oral magnesium may significantly reduce the absorption of the oral bisphosphonates (e.g. risedronate). All medications should be administered at least 30 minutes after a risedronate dose to help prevent these absorption interactions. Some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after oral bisphosphonates or at a completely different time of day. (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Hydrocodone; Ibuprofen: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Ibuprofen: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Ibuprofen; Oxycodone: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Ibuprofen; Pseudoephedrine: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Indomethacin: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Iron Salts: (Moderate) Separating times of administration of the oral bisphosphonate from iron-containing supplements and medications will maximize absorption and clinical benefit. Iron will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any iron containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any iron containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Iron: (Moderate) Separating times of administration of the oral bisphosphonate from iron-containing supplements and medications will maximize absorption and clinical benefit. Iron will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any iron containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any iron containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Ketoprofen: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Ketorolac: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Lansoprazole: (Major) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
    Lansoprazole; Naproxen: (Major) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively. (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Lanthanum Carbonate: (Moderate) To limit absorption problems, the oral bisphosphonates should not be taken within 2 hours of dosing with lanthanum carbonate. Oral drugs known to interact with cationic antacids, like the oral bisphosphonates, may also be bound by lanthanum carbonate. Separating times of administration will maximize absorption and clinical benefit of the bisphosphonate. Separate the times of administration appropriately. Monitor the patient's clinical status and bone density as recommended to ensure the appropriate response to bisphosphonate therapy is obtained.
    Magnesium Citrate: (Moderate) Do not administer oral magnesium-containing products within 2 hours of oral bisphosphonates; oral magnesium may significantly reduce the absorption of the oral bisphosphonates (e.g., alendronate, etidronate, ibandronate, risedronate, or tiludronate). All medications should be administered at least 30 minutes after an alendronate or risedronate dose, and at least 1 hour after an ibandronate dose to help prevent absorption interactions. Some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after these drugs or at a different time of day.
    Magnesium Hydroxide: (Moderate) Magnesium hydroxide will interfere with the absorption of risedronate. Do not take magnesium hydroxide within 2 hours of taking risedronate.
    Magnesium Salts: (Moderate) Oral magnesium may significantly reduce the absorption of the oral bisphosphonates (e.g. risedronate). All medications should be administered at least 30 minutes after a risedronate dose to help prevent these absorption interactions. Some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after oral bisphosphonates or at a completely different time of day.
    Magnesium: (Moderate) Oral magnesium may significantly reduce the absorption of the oral bisphosphonates (e.g. risedronate). All medications should be administered at least 30 minutes after a risedronate dose to help prevent these absorption interactions. Some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after oral bisphosphonates or at a completely different time of day.
    Meclofenamate Sodium: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Mefenamic Acid: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Meloxicam: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Nabumetone: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Naproxen: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Naproxen; Pseudoephedrine: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Naproxen; Sumatriptan: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Nizatidine: (Major) Use of H2-blockers with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets.
    Nonsteroidal antiinflammatory drugs: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Omeprazole: (Major) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
    Omeprazole; Sodium Bicarbonate: (Major) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively. (Moderate) Sodium bicarbonate can reduce the absorption of the oral bisphosphonates. Wait at least 30 minutes after oral alendronate, 1 hour after ibandronate, and 2 hours after oral etidronate, risedronate, or tiludronate before taking a sodium bicarbonatecontaining product.
    Oxaprozin: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Pantoprazole: (Major) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
    Pantothenic Acid, Vitamin B5: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Piroxicam: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Polycarbophil: (Moderate) Coadministration of risedronate with calcium polycarbophil can interfere with the oral absorption of risedronate; do not administer calcium polycarbophil within 30 minutes of risedronate. Each 625 mg of calcium polycarbophil contains a substantial amount of calcium (approximately 125 mg).
    Polysaccharide-Iron Complex: (Moderate) Separating times of administration of the oral bisphosphonate from iron-containing supplements and medications will maximize absorption and clinical benefit. Iron will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any iron containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any iron containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Proton pump inhibitors: (Major) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
    Pyridoxine, Vitamin B6: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Rabeprazole: (Major) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
    Ranitidine: (Major) Use of H2-blockers with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets.
    Rofecoxib: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Sodium Bicarbonate: (Moderate) Sodium bicarbonate can reduce the absorption of the oral bisphosphonates. Wait at least 30 minutes after oral alendronate, 1 hour after ibandronate, and 2 hours after oral etidronate, risedronate, or tiludronate before taking a sodium bicarbonatecontaining product.
    Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Moderate) Separating times of administration of the oral bisphosphonate from iron-containing supplements and medications will maximize absorption and clinical benefit. Iron will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any iron containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any iron containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Sulindac: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Tolmetin: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Valdecoxib: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Vitamin A: (Minor) Doses in excess of 1,500 to 2,000 mcg per day of Vitamin A may lead to bone loss and will counteract the effects of risedronate therapy.
    Zinc Salts: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.

    PREGNANCY AND LACTATION

    Pregnancy

    Risedronate is classified as FDA pregnancy risk category C. After a bisphosphonate is incorporated into bone matrix it is gradually released from the bone, over a period of weeks to years. The extent of bisphosphonate incorporation into adult bone, and hence, the amount available for release back into systemic circulation, is directly related to the total dose and duration of bisphosphonate use. Although there are no data on fetal risk in humans, bisphosphonates do cause fetal harm in animals, suggesting the uptake of bisphosphonates into fetal bone is greater than into maternal bone, and animal reproductive studies indicate risedronate, in particular, may induce fetal skeletal changes and decreases in serum calcium, as well as possibly effect fetal viability. Therefore, there is a theoretical risk of fetal harm if a woman becomes pregnant during or 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 on this risk has not been established. Because of the potential for adverse effects of bisphosphonates in the developing fetus, risedronate should only be used in pregnancy if the potential benefit justifies any possible risk to the mother and fetus. If, during gestation, the fetus is exposed to risedronate, ultrasound of the fetal skeleton should be undertaken.

    It is not known if risedronate is excreted into human breast milk, and data on the use of risedronate during breast-feeding are not available. If risedronate is excreted into human breast milk, the amount secreted is expected to be low due to risedronate's low oral bioavailability and short elimination half-life. Once the mother has discontinued risedronate, secretion into the breast milk is still possible due to the long elimination of risedronate from the bone; however, the amount secreted into the milk should be even lower than when the mother was actively taking risedronate. The effects of risedronate on the nursing infant are not known. Due to the potential effects of bisphosphonates to the infant, until more information is available, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the benefit of the drug to the mother.

    MECHANISM OF ACTION

    Mechanism of Action: Risedronate is a potent antiresorptive agent that does not affect bone mineralization. The inclusion of an amino group within the heterocyclic ring makes risedronate one of the most potent antiresorptive bisphosphonates. As with other bisphosphonates, risedronate inhibits osteoclast formation and activity. Bisphosphonates are internalized by osteoclasts, disrupt the osteoclast cytoskeleton and cause loss of the ruffled border membrane, which is important in the secretion of hydrolytic enzymes and protons. Risedronate can also cause osteoclast apoptosis. The exact molecular mechanism of bisphosphonate bone resorption inhibition has not been determined. The most likely mechanism is that bisphosphonates inhibit intracellular proteins that bind to naturally occurring phosphate-containing or pyrophosphate-containing substrates important to the resorptive process.

    PHARMACOKINETICS

    Risedronate is administered orally. Approximately 60% of the absorbed dose is distributed to the bone with the remainder of the dose excreted in the urine. Unabsorbed drug is eliminated in the feces. Risedronate is not metabolized in the liver and does not induce or inhibit hepatic microsomal drug-metabolizing enzymes. Approximately 50% of the absorbed dose is excreted in the urine within 24 hours. Risedronate elimination is biphasic with an initial half-life of 1.5 hours and a terminal half-life of 220 hours. The extended terminal half-life is thought to be due to risedronate release from bone.

    Oral Route

    Risedronate is absorbed throughout the upper GI tract after oral administration. Differences in time to peak plasma concentration and bioavailability exist between the immediate-release and delayed-release dosage forms; both forms are significantly affected by administration with food. Immediate release tablets achieve Tmax approximately 1 hour after administration, while the Tmax of delayed-release tablets occurs approximately 3 hours after the dose. Bioavailability of 35 mg delayed-release tablets given after a high-fat breakfast and 35 mg immediate-release tablets given 4 hours prior to a meal are similar; however, the bioavailability of the delayed-release tablet is 2- to 4-fold higher than that of the immediate-release tablet administered as indicated (at least 30 minutes prior to breakfast). The average bioavailability of immediate-release risedronate taken 4 hours prior to a meal is 0.63%. Absorption of the immediate-release tablet is decreased by 55% if this dosage form is taken either 0.5 hours prior to breakfast or 2 hours after dinner as compared to absorption in the fasting state, while absorption is decreased by 30% when given 1 hour prior to breakfast as compared to the fasting state. The bioavailability of delayed-release risedronate is decreased by approximately 30% when administered 30 minutes after a high-fat breakfast as compared to when administered 4 hours prior to the morning meal; however, in clinical trials, administration of delayed-release risedronate prior to breakfast, resulted in a higher incidence of abdominal pain. Risedronate is considered effective when immediate-release tablets are given at least 30 minutes prior to breakfast and when delayed-release tablets are given after breakfast. Unabsorbed drug is eliminated in the feces.