(ris ED roe nate)
- Risedronate Sodium
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as sodium:
Actonel: 5 mg, 30 mg, 35 mg
Actonel: 150 mg [contains fd&c blue #2 aluminum lake]
Generic: 5 mg, 30 mg, 35 mg, 150 mg
Tablet Delayed Release, Oral, as sodium:
Atelvia: 35 mg [contains edetate disodium]
Generic: 35 mg
Brand Names: U.S.
- Bisphosphonate Derivative
A bisphosphonate which inhibits bone resorption via actions on osteoclasts or on osteoclast precursors; decreases the rate of bone resorption, leading to an indirect increase in bone mineral density. In Paget's disease, characterized by disordered resorption and formation of bone, inhibition of resorption leads to an indirect decrease in bone formation; but the newly-formed bone has a more normal architecture.
Vd: 13.8 L/kg
Urine (up to 85%); feces (as unabsorbed drug)
Onset of Action
May require weeks
Time to Peak
Serum: 1 to 3 hours
Initial: 1.5 hours; Terminal: 480 to 561 hours
Special Populations: Renal Function Impairment
Clearance decreased ~70% with CrCl 30 mL/minute. Not recommended for use in patients with severe renal impairment. Dosage adjustment is not necessary in patients with CrCl at least 30 mL/minute.
Use: Labeled Indications
Osteoporosis: Treatment and prevention of osteoporosis in postmenopausal women; treatment of osteoporosis in men; treatment and prevention of glucocorticoid-induced osteoporosis
Paget disease: Treatment of Paget disease of the bone
Atelvia, Actonel DR [Canadian product]:
Osteoporosis: Treatment of osteoporosis in postmenopausal women
Hypersensitivity to risedronate, bisphosphonates, or any component of the formulation; hypocalcemia; inability to stand or sit upright for at least 30 minutes; abnormalities of the esophagus (eg, stricture, achalasia) which delay esophageal emptying
Note: Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate. Consider discontinuing after 3 to 5 years of use for osteoporosis in patients at low-risk for fracture.
Paget disease of bone: Oral: Immediate release tablet: 30 mg once daily for 2 months
Note: Re-treatment may be considered (following post-treatment observation of at least 2 months) if relapse occurs, or if treatment fails to normalize serum alkaline phosphatase. For re-treatment, the dose and duration of therapy are the same as for initial treatment. No data are available on more than one course of retreatment. The Endocrine Society guidelines suggest re-treatment may be required between 1 and 5 years (Singer, 2014).
Osteoporosis (postmenopausal): Oral:
Immediate release tablet:
US labeling: Prevention and treatment: 5 mg once daily or 35 mg once weekly or 150 mg once a month
Prevention: 5 mg once daily or 35 mg once weekly
Treatment: 5 mg once daily or 35 mg once weekly or 75 mg once daily for 2 consecutive days per month (150 mg per month) or 150 mg once a month
Delayed release tablet: Treatment: 35 mg once weekly
Osteoporosis (males) treatment: Oral: Immediate release tablet: 35 mg once weekly
Osteoporosis (glucocorticoid-induced) prevention and treatment: Oral: Immediate release tablet: 5 mg once daily
Missed doses: Immediate release tablet:
Once-weekly: If a once-weekly dose is missed, it should be given the next morning after remembered; may then return to the original once-weekly schedule (original scheduled day of the week), however, do not give 2 doses on the same day.
Monthly (150 mg once monthly): If 150 mg once-monthly dose is missed, it should be given the next morning after remembered if the next month’s scheduled dose is >7 days away. If the next month’s scheduled dose is within 7 days, wait until the next month’s scheduled dose. For either scenario, may then return to the original monthly schedule (original scheduled day of the month). Do not give >150 mg within 7 days.
Monthly duet (75 mg once daily for 2 consecutive days): Canadian labeling: If one or both tablets are missed and it is within 7 days of the next scheduled dose, wait until the next month’s scheduled dose. If >7 days until next month’s scheduled doses and only one tablet (75 mg) is missed, take dose in the morning after the day it is remembered; if both of the 75 mg doses are missed, take 75 mg in the morning after the day it is remembered and on the next consecutive morning. May then return to the original monthly schedule. Do not take more than two 75 mg tablets within 7 days.
Refer to adult dosing.
Dosing: Renal Impairment
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: Use is not recommended
Dosing: Hepatic Impairment
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). However, dosage adjustment unlikely because risedronate is not metabolized by the liver.
Oral: Note: Avoid administration of oral calcium supplements, antacids, magnesium supplements/laxatives, and iron preparations within 30 minutes of risedronate administration.
Immediate release tablet: Risedronate immediate release tablets must be taken on an empty stomach with a full glass (6 to 8 oz) of plain water (not mineral water) at least 30 minutes before any food, drink, or other medications orally to avoid interference with absorption. Patient must remain sitting upright or standing for at least 30 minutes after taking (to reduce esophageal irritation). Tablet should be swallowed whole; do not crush or chew.
Delayed release tablet: Risedronate delayed release tablets must be taken with at least 4 oz of plain water (not mineral water) immediately after breakfast. Patient must remain sitting upright or standing for at least 30 minutes after taking (to reduce esophageal irritation). Tablet should be swallowed whole; do not cut, split, crush, or chew.
Ensure adequate calcium and vitamin D intake; if dietary intake is inadequate, dietary supplementation is recommended. Women and men should consume:
Calcium: 1,000 mg/day (men: 50 to 70 years) or 1,200 mg/day (women ≥51 years and men ≥71 years) (IOM 2011; NOF [Cosman 2014])
Vitamin D: 800 to 1,000 int. units daily (men and women ≥50 years) (NOF [Cosman 2014]). Recommended Dietary Allowance (RDA): 600 int. units daily (men and women ≤70 years) or 800 int. units daily (men and women ≥71 years) (IOM 2011).
Take immediate release tablet with at least 6 oz of plain water (not mineral water) ≥30 minutes before the first food or drink of the day other than water. Take delayed release tablet with at least 4 ounces of plain water immediately after breakfast.
Store at 20°C to 25°C (68°F to 77°F).
Aminoglycosides: May enhance the hypocalcemic effect of Bisphosphonate Derivatives. Monitor therapy
Antacids: May decrease the serum concentration of Bisphosphonate Derivatives. Management: Avoid administration of antacids containing polyvalent cations within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Exceptions: Magaldrate; Sodium Bicarbonate. Consider therapy modification
Calcium Salts: May decrease the serum concentration of Bisphosphonate Derivatives. Management: Avoid administration of oral calcium supplements within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Consider therapy modification
Deferasirox: Bisphosphonate Derivatives may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy
H2-Antagonists: May increase the serum concentration of Risedronate. This applies specifically to delayed-release risedronate. Avoid combination
Iron Salts: May decrease the serum concentration of Bisphosphonate Derivatives. Management: Avoid administration of oral iron supplements within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Exceptions: Ferric Carboxymaltose; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Consider therapy modification
Magnesium Salts: May decrease the serum concentration of Bisphosphonate Derivatives. Management: Avoid administration of oral magnesium salts within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Consider therapy modification
Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Bisphosphonate Derivatives. Specifically, polyvalent cation-containing multivitamins may decrease the absorption of orally-administered bisphosphonate derivatives. Management: Avoid administration of polyvalent cation-containing multivitamins within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Consider therapy modification
Multivitamins/Minerals (with AE, No Iron): May decrease the serum concentration of Bisphosphonate Derivatives. Specifically, polyvalent cation-containing multivitamins may decrease the absorption of orally-administered bisphosphonate derivatives. Management: Avoid administration of polyvalent cation-containing multivitamins within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern. Monitor therapy
Proton Pump Inhibitors: May diminish the therapeutic effect of Risedronate. Proton Pump Inhibitors may increase the serum concentration of Risedronate. This applies specifically to use of delayed-release risedronate. Avoid combination
Systemic Angiogenesis Inhibitors: May enhance the adverse/toxic effect of Bisphosphonate Derivatives. Specifically, the risk for osteonecrosis of the jaw may be increased. Monitor therapy
Bisphosphonates may interfere with diagnostic imaging agents such as technetium-99m-diphosphonate in bone scans.
Frequency may vary with product, dose, and indication.
Cardiovascular: Hypertension (11%)
Central nervous system: Headache (3% to 18%)
Dermatologic: Skin rash (8% to 12%)
Gastrointestinal: Gastrointestinal disease (perforations, ulcers, or bleeding; 51%), diarrhea (5% to 20%), nausea (4% to 13%), abdominal pain (2% to 12%)
Genitourinary: Urinary tract infection (11%)
Infection: Infection (31%)
Neuromuscular & skeletal: Arthralgia (7% to 33%), back pain (6% to 28%)
1% to 10%:
Cardiovascular: Peripheral edema (8%), chest pain (7%), cardiac arrhythmia (2%)
Central nervous system: Depression (7%), dizziness (3% to 7%)
Endocrine & metabolic: Increased parathyroid hormone (8% to 9%; >1.5 x ULN: ≤2%), hypocalcemia (≤5%), hypophosphatemia (<3% decrease from baseline)
Gastrointestinal: Dyspepsia (4% to 8%), constipation (3% to 7%), vomiting (2% to 5%), gastritis (1% to 3%), gastroesophageal reflux disease (1% to 2%), duodenitis (≤1%), glossitis (≤1%)
Genitourinary: Benign prostatic hyperplasia (5%), nephrolithiasis (3%)
Hypersensitivity: Acute phase reaction-like symptoms (≤8%; includes fever, influenza-like illness)
Infection: Influenza (6% to 7%)
Neuromuscular & skeletal: Arthropathy (7%), myalgia (1% to 7%), limb pain (2% to 4%), musculoskeletal pain (2%), muscle spasm (1% to 2%)
Ophthalmic: Cataract (7%)
Respiratory: Flu-like symptoms (10%), pharyngitis (6%), rhinitis (6%), bronchitis (4%), upper respiratory tract infection (3% to 4%)
<1% (Limited to important or life-threatening): Esophageal ulcer, esophagitis, exacerbation of asthma, gastric ulcer, hypersensitivity reaction, osteonecrosis (primarily of the jaw), Stevens-Johnson syndrome, toxic epidermal necrolysis
Concerns related to adverse effects:
• Bone fractures: Atypical femur fractures have been reported in patients receiving bisphosphonates for treatment/prevention of osteoporosis. The fractures include subtrochanteric femur (bone just below the hip joint) and diaphyseal femur (long segment of the thigh bone). Some patients experience prodromal pain weeks or months before the fracture occurs. It is unclear if bisphosphonate therapy is the cause for these fractures, although the majority of cases have been reported in patients taking bisphosphonates. Patients receiving long-term (>3 to 5 years) therapy may be at an increased risk. Discontinue bisphosphonate therapy in patients who develop a femoral shaft fracture.
• Bone/joint/muscle pain: Infrequently, severe (and occasionally debilitating) bone, joint, and/or muscle pain have been reported during bisphosphonate treatment. The onset of pain ranged from a single day to several months. Consider discontinuing therapy in patients who experience severe symptoms; symptoms usually resolve upon discontinuation. Some patients experienced recurrence when rechallenged with same drug or another bisphosphonate; avoid use in patients with a history of these symptoms in association with bisphosphonate therapy.
• Gastrointestinal mucosa irritation: May cause irritation to upper gastrointestinal mucosa. Dysphagia, esophagitis, esophageal or gastric ulcers, esophageal erosions, and esophageal stricture (rare) have been reported with oral bisphosphonates; risk increases in patients unable to comply with dosing instructions. Use with caution in patients with dysphagia, esophageal disease, gastritis, duodenitis, or ulcers (may worsen underlying condition). Discontinue if new or worsening symptoms occur.
• Osteonecrosis of the jaw: Osteonecrosis of the jaw (ONJ), also referred to as medication-related osteonecrosis of the jaw (MRONJ), has been reported in patients receiving bisphosphonates. Known risk factors for MRONJ include invasive dental procedures (eg, tooth extraction, dental implants, boney surgery), cancer diagnosis, concomitant therapy (eg, chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, ill-fitting dentures, and comorbid disorders (anemia, coagulopathy, infection, preexisting dental or periodontal disease). Risk may increase with increased duration of bisphosphonate use. According to a position paper by the American Association of Maxillofacial Surgeons (AAOMS), MRONJ has been associated with bisphosphonate and other antiresorptive agents (denosumab), and antiangiogenic agents (eg, bevacizumab, sunitinib) used for the treatment of osteoporosis or malignancy; risk of MRONJ is significantly higher in cancer patients receiving antiresorptive therapy compared to patients receiving osteoporosis treatment (regardless of medication used or dosing schedule). MRONJ risk is also increased with IV antiresorptive use compared to the minimal risk associated with oral bisphosphonate use, although risk appears to increase with oral bisphosphonates when duration of therapy exceeds 4 years (AAOMS [Ruggiero 2014]). The manufacturer’s labeling states that in patients requiring invasive dental procedures, discontinuing bisphosphonates may reduce the risk of ONJ and clinical judgment should guide the decision. However, the AAOMS suggests there is currently no evidence that interrupting oral bisphosphonate therapy alters the risk of ONJ following tooth extraction, and that in patients receiving oral bisphosphonates for <4 years who have no clinical risk factors, no alternations or delay in any procedure common to oral/maxillofacial surgeons, periodontists, and other dental providers is necessary (special considerations apply to patients receiving dental implants). Conversely, in patients receiving oral bisphosphonates for >4 years or in patients receiving oral bisphosphonates for <4 years who have also taken corticosteroids or antiangiogenic medications concomitantly, the AAOMS recommends considering a 2-month drug free period prior to invasive dental procedures (recommendation based on a theoretical benefit) Patients developing ONJ during therapy should receive care by an oral surgeon (AAOMS [Ruggiero 2014]). According to the manufacturer, discontinuation of the bisphosphonate therapy should be considered (based on risk/benefit evaluation) in patients who develop ONJ.
• Glucocorticoid-induced osteoporosis: Evaluate sex steroid hormonal status prior to treatment initiation; consider appropriate hormone replacement if necessary.
• Hypocalcemia: Before initiation of therapy hypocalcemia must be corrected; ensure adequate calcium and vitamin D intake, especially for patients with Paget disease in whom the pretreatment rate of bone turnover may be greatly elevated.
• Renal impairment: Use with caution in patients with renal impairment (not recommended in patients with a CrCl <30 mL/minute).
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Pediatric: Not approved for use in pediatric patients with osteogenesis imperfecta due to lack of efficacy in reducing the risk of fracture.
• Duration of therapy: In the management of osteoporosis, re-evaluate the need for continued therapy periodically; the optimal duration of treatment has not yet been determined. Consider discontinuing after 3 to 5 years of use in patients at low-risk for fracture; following discontinuation, re-evaluate fracture risk periodically.
Osteoporosis: Bone mineral density (BMD) should be evaluated 1 to 2 years after initiating therapy and every 2 years thereafter (NOF [Cosman 2014] in patients with combined risedronate and glucocorticoid treatment, BMD should be made at initiation and repeated after 6 to 12 months; annual measurements of height and weight, assessment of chronic back pain; serum calcium and 25(OH)D; consider measuring biochemical markers of bone turnover
Paget disease: Alkaline phosphatase at 6 to 12 weeks for initial response to treatment (when bone turnover will have shown a substantial decline) and potentially at 6 months (maximal suppression of high bone turnover); following treatment completion, monitor at ~6- to 12-month intervals (Singer, 2014); monitoring more specific biochemical markers of bone turnover (eg, serum P1NP, NTX, serum beta-CTx) is generally only warranted in patients with Paget disease who have abnormal liver or biliary tract function or when early assessment of response to treatment is needed (eg, spinal compression, very active disease) (Singer, 2014); serum calcium and 25(OH)D; pain
Pregnancy Risk Factor
Adverse events were observed in some animal reproduction studies. It is not known if bisphosphonates cross the placenta, but fetal exposure is expected (Djokanovic, 2008; Stathopoulos, 2011). Bisphosphonates are incorporated into the bone matrix and gradually released over time. The amount available in the systemic circulation varies by dose and duration of therapy. Theoretically, there may be a risk of fetal harm when pregnancy follows the completion of therapy; however, available data have not shown that exposure to bisphosphonates during pregnancy significantly increases the risk of adverse fetal events (Djokanovic, 2008; Levy, 2009; Stathopoulos, 2011). Until additional data is available, most sources recommend discontinuing bisphosphonate therapy in women of reproductive potential as early as possible prior to a planned pregnancy; use in premenopausal women should be reserved for special circumstances when rapid bone loss is occurring (Bhalla, 2010; Pereira, 2012; Stathopoulos, 2011). Because hypocalcemia has been described following in utero bisphosphonate exposure, exposed infants should be monitored for hypocalcemia after birth (Djokanovic, 2008; Stathopoulos, 2011).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience constipation, diarrhea, back pain, or flu-like symptoms. Have patient report immediately to prescriber signs of low calcium (muscle cramps or spasms, numbness and tingling, or seizures); black, tarry, or bloody stools; angina; coughing up blood; severe nausea; severe vomiting; vomiting blood; severe abdominal pain; heartburn; dysphagia; painful swallowing; pharyngitis; severe bone pain; severe joint pain; severe muscle pain; groin, hip, or thigh pain; severe headache; severe dizziness; vision changes; difficult urination; painful urination; eye pain; eye irritation; jaw pain or edema, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.