Class: Bone Resorption Inhibitors
VA Class: HS900
Chemical Name: [1-hydroxy-2-(3-pyridinyl)ethylidene]bis-phosphonic acid monosodium salt
Molecular Formula: C7H10NNaO7P2
CAS Number: 115436-72-1
Brands: Actonel
Special Alerts:
[Posted 07/21/2011] ISSUE: FDA notified healthcare professionals and patients about its ongoing review of data from published studies to evaluate whether use of oral bisphosphonate drugs is associated with an increased risk of cancer of the esophagus. FDA has not concluded that taking an oral bisphosphonate drug increases the risk of esophageal cancer. There are insufficient data to recommend endoscopic screening of asymptomatic patients. FDA will continue to evaluate all available data supporting the safety and effectiveness of bisphosphonate drugs and will update the public when more information becomes available.
BACKGROUND: Oral bisphosphonates are commonly used for the prevention and treatment of osteoporosis as well as to treat other bone diseases such as Paget’s disease. There have been conflicting findings from studies evaluating the risk of esophageal cancer. Esophagitis and other esophageal events have been reported, particularly in patients who do not follow the specific directions for use of oral bisphosphonates. See the Data Summary in the Drug Safety Communication for additional details at: .
RECOMMENDATION: Patients should talk with their healthcare professional about the benefits and risks of taking oral bisphosphonates and how long they should expect to take them. Patients should talk with their healthcare professional if they develop swallowing difficulties, chest pain, new or worsening heartburn, or have trouble or pain when swallowing. Patients should be instructed to carefully follow the directions for use of the oral bisphosphonate drug they are prescribed. For more information visit the FDA website at: and .
[Posted 10/13/2010] ISSUE: FDA is updating the public regarding information previously communicated describing the risk of atypical fractures of the thigh, known as subtrochanteric and diaphyseal femur fractures, in patients who take bisphosphonates for osteoporosis. This information will be added to the Warnings and Precautions section of the labels approved to treat osteoporosis, including alendronate (Fosamax), alendronate with cholecalciferol (Fosamax Plus D), risedronate (Actonel and Atelvia), risedronate with calcium carbonate (Actonel with Calcium), ibandronate (Boniva), tiludronate (Skelid), and zoledronic acid (Reclast) and their generic products. A Medication Guide will also be required to be given to patients when they pick up their bisphosphonate prescription.
BACKGROUND: Atypical subtrochanteric femur fractures are fractures in the bone just below the hip joint. Diaphyseal femur fractures occur in the long part of the thigh bone. These fractures are very uncommon and appear to account for less than 1% of all hip and femur fractures overall. Although it is not clear if bisphosphonates are the cause, these unusual femur fractures have been predominantly reported in patients taking bisphosphonates.
RECOMMENDATIONS: Patients should continue to take their medication unless told to stop by their healthcare professional. FDA recommends that healthcare professionals should discontinue potent antiresorptive medications (including bisphosphonates) in patients who have evidence of a femoral shaft fracture. For more information visit the FDA website at: and .
[Posted 03/11/2010] FDA notified healthcare professionals and patients that at this point, the data that FDA has reviewed have not shown a clear connection between bisphosphonate use and a risk of atypical subtrochanteric femur fractures. FDA is working with outside experts, including members of the recently convened American Society of Bone and Mineral Research Subtrochanteric Femoral Fracture Task Force, to gather more information and evaluate the issue further.
FDA recommends that healthcare professionals follow the recommendations in the drug label when prescribing oral bisphosphonates.
Patients should continue taking oral bisphosphonates unless told by their healthcare professional to stop. Patients should talk to their healthcare professional if they develop new hip or thigh pain or have any concerns with their medications. For more information visit the FDA website at: and .
[Posted 11/12/2008] FDA issued an update to the Agency’s review of safety data regarding the potential increased risk of atrial fibrillation in patients treated with a bisphosphonate drug. Bisphosphonates are a class of drugs used primarily to increase bone mass and reduce the risk for fracture in patients with osteoporosis, slow bone turnover in patients with Paget’s disease of the bone, and to treat bone metastases and lower elevated levels of blood calcium in patients with cancer. FDA reviewed data on 19,687 bisphosphonate-treated patients and 18,358 placebo-treated patients who were followed for 6 months to 3 years. The occurrence of atrial fibrillation was rare within each study, with most studies containing 2 or fewer events. Across all studies, no clear association between overall bisphosphonate exposure and the rate of serious or non-serious atrial fibrillation was observed. Additionally, increasing dose or duration of bisphosphonate therapy was not associated with an increase rate of atrial fibrillation. Healthcare professionals should not alter their prescribing patterns for bisphosphonates and patients should not stop taking their bisphosphonate medication. For more information visit the FDA website at: , and .
[Posted 01/07/2008] FDA informed healthcare professionals and patients of the possibility of severe and sometimes incapacitating bone, joint, and/or muscle (musculoskeletal) pain in patients taking bisphosphonates. Although severe musculoskeletal pain is included in the prescribing information for all bisphosphonates, the association between bisphosphonates and severe musculoskeletal pain may be overlooked by healthcare professionals, delaying diagnosis, prolonging pain and/or impairment, and necessitating the use of analgesics. The severe musculoskeletal pain may occur within days, months, or years after starting a bisphosphonates. Some patients have reported complete relief of symptoms after discontinuing the bisphosphonate, whereas others have reported slow or incomplete resolution. The risk factors for and incidence of severe musculoskeletal pain associated with bisphosphonates are unknown.
Healthcare professionals should consider whether bisphosphonate use might be responsible for severe musculoskeletal pain in patients who present with these symptoms and consider temporary or permanent discontinuation of the drug. For more information visit the FDA website at: and .
[Posted 10/01/2007] FDA issued an early communication about the ongoing review of new safety data regarding the association of atrial fibrillation with the use of bisphosphonates. Bisphosphonates are a class of drugs used primarily to increase bone mass and reduce the risk for fracture in patients with osteoporosis, slow bone turnover in patients with Paget’s disease of the bone, treat bone metastases, and lower elevated levels of blood calcium in patients with cancer.
FDA reviewed spontaneous postmarketing reports of atrial fibrillation reported in association with oral and intravenous bisphosphonates and did not identify a population of bisphosphonate users at increased risk of atrial fibrillation. In addition, as part of the data review for the recent approval of once-yearly Reclast for the treatment of postmenopausal osteoporosis, FDA evaluated the possible association between atrial fibrillation and the use of Reclast (zoledronic acid). Most cases of atrial fibrillation occurred more than a month after drug infusion. Also, in a subset of patients monitored by electrocardiogram up to the 11th day following infusion, there was no significant difference in the prevalence of atrial fibrillation between patients who received Reclast and patients who received placebo.
Upon initial review, it is unclear how these data on serious atrial fibrillation should be interpreted. Therefore, FDA does not believe that healthcare providers or patients should change either their prescribing practices or their use of bisphosphonates at this time. For more information visit the FDA website at: and .
REMS:
FDA approved a REMS for risedronate to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().
Introduction
Synthetic bisphosphonate; bone resorption inhibitor.1 2 4 5 6 8 9 12 13 14
Uses for Risedronate Sodium
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Osteoporosis
Prevention of osteoporosis in postmenopausal women with risk factors for development of osteoporosis.1 3 17 Risk factors include premature ovarian failure; family history of osteoporosis; a small, slim body frame; cigarette smoking; excessive alcohol use; low dietary calcium intake; sedentary lifestyle; or Caucasian or Asian race.1 3 17
Treatment of osteoporosis in postmenopausal women.1 5 6 7
May be used concomitantly with hormone replacement therapy.1
Corticosteroid-induced Osteoporosis
Prevention of corticosteroid-induced osteoporosis in patients initiating therapy with corticosteroids (daily dosage ≥7.5 mg of prednisone).1 8 10
Treatment of corticosteroid-induced osteoporosis in patients receiving corticosteroids (daily dosage ≥7.5 mg of prednisone).1 4 9 10 11
American College of Rheumatology considers patients receiving ≥5 mg of prednisone daily for ≥3 months at risk for bone loss.21 Recommends bisphosphonate therapy for all long-term corticosteroid-treated men, premenopausal women (with caution), and postmenopausal women with or without hormone replacement therapy (combined estrogen and progestin therapy).21
Paget’s Disease of Bone
Treatment of Paget’s disease of bone (osteitis deformans)1 2 13 in patients with serum alkaline phosphatase concentrations at least twice ULN or who are symptomatic or at risk for future complications.1
Risedronate Sodium Dosage and Administration
General
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Use adjunctively with other measures (e.g., weight-bearing exercise, reduction in smoking and alcohol use) to retard further bone loss.1 4
Supplemental calcium and vitamin D recommended if daily dietary intake is inadequate, particularly in patients with Paget’s disease of bone or receiving corticosteroids.a
Administration
Administer orally1 3 5 6 7 8 9 10 with a full glass (180–240 mL) of plain water at least 30 minutes before the first food or beverage of the day.1 3
Administer in an upright position (sitting or standing).1 3 Avoid lying down for at least 30 minutes following administration.1 3 (See GI Effects under Cautions.)
Do not suck or chew tablets; potential for oropharyngeal irritation.1 3 (See GI Effects under Cautions.)
Do not administer at the same time as other beverages, foods, or mineral supplements containing calcium, aluminum, or magnesium.5 a b (See Antacids or Mineral Supplements Containing Divalent Cations under Interactions.)
If a weekly dose is missed, administer the missed dose the morning after it is remembered, followed by resumption of the regular weekly schedule.1 3 Do not take 2 risedronate sodium 35-mg tablets on the same day.1 3
Dosage
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Available as risedronate sodium; dosage expressed in terms of the salt.18
Adults
Osteoporosis
Prevention of Postmenopausal Osteoporosis
Oral
5 mg once daily or 35 mg once weekly.1
Treatment of Postmenopausal Osteoporosis
Oral
5 mg once daily or 35mg once weekly.1
Corticosteroid-induced Osteoporosis
Prevention of Corticosteroid-induced Osteoporosis
Oral
5 mg once daily.1
Continue risedronate as long as patient continues to receive corticosteroid therapy.21
Treatment of Corticosteroid-induced Osteoporosis
Oral
5 mg once daily.1
Continue risedronate as long as patient continues to receive corticosteroid therapy.21
Paget’s Disease of Bone
Oral
30 mg once daily for 2 months.1 2
Consider retreatment (same dosage and duration) after a 2-month posttreatment evaluation period if relapse occurs or if initial treatment failed to normalize serum alkaline phosphatase concentrations.1
Prescribing Limits
Adults
Paget’s Disease of Bone
Oral
Safety and efficacy not established for >1 course of retreatment.1
Special Populations
Hepatic Impairment
Dosage adjustments are not necessary.1
Renal Impairment
Dosage adjustments are not necessary in patients with mild to moderate impairment (Clcr ≥30 mL/minute).1 Use is not recommended in patients with severe impairment (Clcr <30 mL/minute).1
Cautions for Risedronate Sodium
Contraindications
Warnings/Precautions
Warnings
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
GI Effects
Possible dysphagia, esophagitis, or esophageal or gastric ulcer.1 12 15 16 (See Administration under Dosage and Administration.)
General Precautions
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Metabolic Effects
Possible asymptomatic decreases in serum calcium and phosphorus concentrations.1
Correct hypocalcemia and other disturbances of bone and mineral metabolism before initiating therapy.1 If daily dietary intake is inadequate, administer supplemental calcium and vitamin D.1
Endocrine Effects
Before initiating therapy in patients receiving long-term corticosteroid therapy, measure sex hormones and consider replacement therapy, if appropriate.1 4 11
Specific Populations
Pregnancy
Category C.1
Lactation
Distributed into milk in rats.1 Discontinue nursing or the drug.1
Pediatric Use
Safety and efficacy not established.1
Geriatric Use
No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1
Men
Safety and efficacy not established for treatment of osteoporosis unrelated to corticosteroid use.1
Hepatic Impairment
Safety and efficacy not established.1
Renal Impairment
Decreased clearance; use not recommended in patients with severe renal impairment (Clcr <30 mL/minute).1 (See Renal Impairment under Dosage and Administration.)
Common Adverse Effects
Pain (e.g., back,1 8 10 chest,1 unspecified1 ), hypertension,1 flu-like syndrome,1 diarrhea,1 arthralgia,1 8 10 infection (unspecified).1
Interactions for Risedronate Sodium
Does not induce or inhibit CYP isoenzymes and is not metabolized.a
Antacids or Mineral Supplements Containing Divalent Cations
Potential decreased risedronate absorption when administered with divalent cations (e.g., aluminum, calcium, magnesium).1
Drugs Affecting Hepatic Microsomal Enzymes
Pharmacokinetic interaction unlikely.1
Specific Drugs
Drug
|
Interaction
|
Comments
|
|---|
Histamine H2-receptor antagonists
|
No evidence of increased adverse upper GI effects1
|
|
Hormone replacement therapy
|
Potential additive effects on bone mineral density1 18 20 a
|
|
NSAIAs
|
No evidence of increased adverse upper GI effects1
|
|
Proton pump inhibitors
|
No evidence of increased adverse upper GI effects1
|
|
Risedronate Sodium Pharmacokinetics
Absorption
Bioavailability
The mean absolute oral bioavailability is 0.63%.1
Onset
Reduction of bone turnover evident within 14 days of beginning therapy; maximal effects observed in about 6 months.a
Food
When administered 30 minutes or 1 hour prior to breakfast, the extent of absorption is reduced by 55 or 30%, respectively, compared to the fasting state.1 However, drug is effective when administered at least 30 minutes before breakfast.a
Distribution
Extent
Mean steady-state volume of distribution is 6.3 L/kg.1 In animal studies, 60% of a dose distributed into bone.1
Animal data indicate that the drug crosses placenta and is distributed into fetal bones.a
Distributed into milk in animals.1 Not known whether the drug is distributed into human milk.1
Plasma Protein Binding
About 24%.1
Elimination
Metabolism
There is no evidence of systemic metabolism.a
Elimination Route
Eliminated mainly in urine; only unabsorbed drug is excreted in feces.1
Half-life
Initial half-life is about 1.5 hours and terminal exponential half-life is 480 hours.1 The terminal half-life is thought to represent the dissociation of the drug from the surface of bone.1
Special Populations
Renal clearance is decreased by 70% in patients with severe renal impairment (i.e., Clcr <30 mL/minute).a
Stability
Storage
Oral
Tablets
20–25 °C.a
Actions and Spectrum
Advice to Patients
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Importance of providing a copy of the manufacturer’s patient information.1 3
Importance of proper administration (e.g., avoiding foods and beverages other than plain water, not lying down for 30 minutes following administration).1 3
Importance of swallowing tablets whole, without crushing, chewing, or sucking.1
Importance of discontinuing and informing clinician if symptoms of esophageal disease (e.g., difficulty or pain on swallowing; retrosternal, abdominal, or esophageal pain; severe or persistent heartburn) develop.1 3
Importance of adhering to recommended life-style modifications (e.g., weight-bearing exercise, calcium and vitamin D consumption, avoidance of excessive cigarette smoking and/or alcohol consumption).1 3
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 3
Importance of informing clinicians of severe kidney disease.3
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1
Importance of advising patients of other important precautionary information.1 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Risedronate Sodium
Routes
|
Dosage Forms
|
Strengths
|
Brand Names
|
Manufacturer
|
|---|
Oral
|
Tablets, film-coated
|
5 mg
|
Actonel
|
Procter & Gamble
|
|
|
30 mg
|
Actonel
|
Procter & Gamble
|
|
|
35 mg
|
Actonel
|
Procter & Gamble
|
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Actonel 150MG Tablets (WARNER CHILCOTT PHARMA): 1/$144.55 or 3/$409.44
Actonel 30MG Tablets (WARNER CHILCOTT PHARMA): 10/$297.83 or 30/$867.40
Actonel 5MG Tablets (WARNER CHILCOTT PHARMA): 30/$140.99 or 90/$395.99
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
References
1. Procter & Gamble Pharmaceuticals. Actonel (risedronate sodium) tablets prescribing information. Cincinnati, OH; 2000 Apr.
2. Miller PD, Brown JP, Siris ES et al. A randomized, double-blind comparison of risedronate and etidronate in the treatment of Paget’s disease of bone. Am J Med. 1999; 106:513-20. [IDIS 428270] [PubMed 10335722]
3. Procter & Gamble Pharmaceuticals. Actonel (risedronate sodium) tablets patient information. Cincinnati, OH; 2000 Apr.
4. American College of Rheumatology Task Force on Osteoporosis Guidelines. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheum. 1996; 39:1791-801. [IDIS 375200] [PubMed 8912500]
5. Fogelman I, Ribot C, Smith R et al. Risedronate reverses bone loss in postmenopausal women with low bone mass: results from a multinational, double-blind, placebo-controlled trial. J Clin Endocrinol Metab. 2000; 85:1895-900. [IDIS 446998] [PubMed 10843171]
6. Harris ST, Watts NB, Genant HK et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. JAMA. 1999; 282:1344-52. [IDIS 433492] [PubMed 10527181]
7. Reginster J, Minne HW, Sorensen OH et al. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral efficacy with risedronate therapy (VERT) study group. Osteoporos Int. 2000; 11:83-91. [PubMed 10663363]
8. Cohen S, Levy RM, Keller M et al. Risedronate therapy prevents corticosteroid-induced bone loss: a twelve-month, randomized, double-blind, placebo-controlled, parallel group study. Arthritis Rheum. 1999; 42:2309-18. [IDIS 438381] [PubMed 10555025]
9. Reid DM, Hughes RA, Laan RF et al. Efficacy and safety of daily risedronate in the treatment of corticosteroid-induced osteoporosis in men and women: a randomized trial. European Corticosteroid-induced osteoporosis treatment study. J Bone Miner Res. 2000; 15:1006-13. [PubMed 10841169]
10. Wallach S, Cohen S, Reid DM et al. Effects of risedronate treatment on bone density and vertebral fracture in patients on corticosteroid therapy. Calcif Tissue Int. 2000; 67:277-85. [PubMed 11000340]
11. Eastell R, Reid DM, Compston J et al. A UK Consensus Group on management of glucocorticoid-induced osteoporosis: an update. J Int Med. 1998; 244:271-92.
12. Lourwood DL. The pharmacology and therapeutic utility of bisphosphonates. Pharmacotherapy. 1998; 18:779-89. [IDIS 415603] [PubMed 9692651]
13. Anon. Risedronate for Paget’s disease of bone. Med Lett Drugs Ther. 1998; 40:87-8. [PubMed 9731243]
14. Goa KL, Balfour JA. Risedronate. Drugs Aging. 1998; 13:83-91. [PubMed 9679211]
15. Patel S. Risedronate: a viewpoint. Drugs Aging. 1998; 13:92.
16. Johnston CC. Risedronate: a viewpoint. Drugs Aging. 1998; 13:92.
17. National Osteoporosis Foundation. Physician’s guide to prevention and treatment of osteoporosis. Washington, DC; 2000. From National Osteoporosis Foundation web site ().
18. Procter & Gamble Pharmaceuticals, Cincinnati, OH: Personal communication.
19. Hooper M, Ebeling P, Roberts A et al. Risedronate prevents bone loss in early postmenopausal women. Calcif Tissue Int. 1999; 64(Suppl 1):S69.
20. Harris ST, Wasnich R, Ettinger M et al. The effects of risedronate plus estrogen compared with estrogen alone in postmenopausal women. J Bone Miner Res. 1999; 14(Suppl 1):S410.
21. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-induced Osteoporosis. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update. Arthritis Rheum. 2001; 44:1496-503. [IDIS 466759] [PubMed 11465699]
22. Sambrook PN. Corticosteroid osteoporosis: practical implications of recent trials. J Bone Miner Res. 2000; 15:1645-9. [PubMed 10976984]
23. Plotkin LI, Weinstein RS, Parfitt AM et al. Prevention of osteocyte and osteoblast apoptosis by biphosphonates and calcitonin. J Clin Invest. 1999; 104:1363-74. [PubMed 10562298]
24. Adachi JD, Bensen WG, Brown J et al. Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis. N Engl J Med. 1997; 337:382-7. [IDIS 389180] [PubMed 9241127]
25. Roux C, Oriente P, Laan R et al. Randomized trial of effect of cyclical etidronate in the prevention of corticosteroid-induced bone loss. J Clin Endocrinol Metab. 1998; 83:1128-33. [IDIS 404610] [PubMed 9543129]
26. Adachi JD, Saag KG, Delmas PD et al. Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double-blind, placebo-controlled extension trial. Arthritis Rheum. 2001; 44:202-11. [PubMed 11212161]
27. Brown JP, Kendler DL, McClung MR et al. The efficacy and tolerability of risedronate once a week for the treatment of postmenopausal osteoporosis. Calcif Tissue Int. 2002; 71:103-11. [PubMed 12085156]
a. Procter & Gamble Pharmaceuticals. Actonel (risedronate sodium) tablets prescribing information. Cincinnati, OH; 2003 Mar.
b. Procter & Gamble Pharmaceuticals. Actonel (risedronate sodium) tablets patient information. Cincinnati, OH; 2002 Mar. Available at . Accessed 2003 Sep 23.
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- Risedronate Sodium Drug Interactions
- Risedronate Sodium Support Group
- 5 Reviews for Risedronate Sodium - Add your own review/rating
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