Class: Bone Resorption Inhibitors
VA Class: HS900
Chemical Name: [1-Hydroxy-3-(methylpentylamino)propylidene]diphosphonate trihydrogen sodium monohydrate
Molecular Formula: C9H22NNaO7
CAS Number: 138926-19-9
Uses for Ibandronate Sodium
Prevention of osteoporosis in postmenopausal women.1 Risk factors include premature ovarian failure, family history of osteoporosis, endocrine disorders (e.g., thyrotoxicosis, hyperparathyroidism, Cushing’s syndrome, hyperprolactinemia, insulin-dependent diabetes mellitus), early menopause, previous fracture, high bone turnover, reduced bone mineral density (≥1 standard deviation below premenopausal mean), thin body frame, low body weight, white or Asian race, excessive alcohol intake, treatment with certain drugs (e.g., corticosteroids), low dietary calcium or vitamin D intake, sedentary lifestyle, and cigarette smoking.5 6 8 18 42 43
Ibandronate Sodium Dosage and Administration
Administer orally with a full glass (180–240 mL) of plain water ≥60 minutes prior to the first food, beverage (other than plain water), or other orally administered drug or supplement (including vitamins, antacids, and calcium) of the day.1 4 5 16 (See Food under Pharmacokinetics.)
When administered monthly, take tablets in the morning on the same day each month.1 5 If a monthly dose is missed and the next scheduled dose is more than 7 days away, take the missed dose the next morning after it is remembered and resume the regular schedule.1 5 If the next scheduled dose is 1–7 days away, maintain the regular schedule;1 do not take more than one 150-mg tablet within the same week.1 5
Administer by IV injection once every 3 months by a health-care professional.7
If a dose is missed, reschedule administration with a health-care professional as soon as possible.7 8 Schedule subsequent injections at 3-month intervals; should not be administered more often than once every 3 months.7 8
Take care to avoid intra-arterial or paravenous injection as such administration could result in tissue damage.7
Rate of Administration
Prevention in Postmenopausal WomenOral
Treatment in Postmenopausal WomenOral
2.5 mg once daily or 150 mg once monthly.1
Optimal duration of treatment not established.1 28 Safety and efficacy based on data supporting fracture reduction over 3 years of treatment.1 28 Reevaluate need for continued therapy periodically in all patients receiving bisphosphonates.1 28
3 mg once every 3 months.7
Optimal duration of treatment not established.7 28 Safety and efficacy of IV ibandronate based on data supporting fracture reduction over 1 year of treatment.7 Reevaluate need for continued therapy periodically in all patients receiving bisphosphonates.7 28
Cautions for Ibandronate Sodium
Upper GI Effects
Possible severe adverse esophageal effects (e.g., esophagitis, esophageal ulcers, erosions, strictures, perforation).1 2 (See Oral Administration under Dosage and Administration.) Monitor for any manifestations and discontinue if dysphagia, odynophagia, new or worsening heartburn, or retrosternal pain occurs.1
Use with caution in patients with history of upper GI disease (e.g., Barrett’s esophagus, dysphagia, other esophageal diseases, gastritis, duodenitis, ulcers).1 Gastric and duodenal ulcers (some severe and with complications) reported during postmarketing experience.1
Route of Administration
Injection must be administered IV by a health-care professional; do not administer by non-IV (e.g., intra-arterial) routes.7 (See Administration Risks under Dosage and Administration.)
Like other bisphosphonates, may cause transient decrease in serum calcium concentrations when given IV.7
Osteonecrosis and osteomyelitis of the jaw reported in patients receiving bisphosphonates, usually when given IV.1 7 13 Associated mostly with dental procedures (e.g., tooth extraction) in cancer patients, but some cases occurred in patients with postmenopausal osteoporosis or other diagnoses.1 7 13 Known risk factors include cancer, chemotherapy, radiation therapy, corticosteroids, poor oral hygiene, preexisting dental disease, anemia, coagulopathy, and infection.1 7
In patients requiring dental procedures, no data are available to suggest whether discontinuance of therapy prior to procedure reduces the risk of osteonecrosis of the jaw.1 7 Base management of patients requiring dental treatment on an individual assessment of risks and benefits.1 7
Severe and occasionally incapacitating bone, joint, and/or muscle pain reported infrequently with bisphosphonate therapy.1 5 7 8 18 Time to onset varied from 1 day to years (mean onset about 3 months) after treatment initiation.1 7 8 20 If severe symptoms occur, consider discontinuing drug.1 Such pain generally improves following discontinuance, but may recur upon subsequent rechallenge with the same drug or another bisphosphonate.1 5 7 8 18
Atypical (subtrochanteric or diaphyseal) femur fractures reported rarely with long-term use (>3 years) of bisphosphonates, mostly in patients receiving these drugs for osteoporosis.28 29 30 31 Often occurs with minimal or no trauma, and may be bilateral.26 27 28 30 33 Causality not established; atypical fractures also occur in osteoporotic patients not receiving bisphosphonates.28 29 30 31 Risk may be increased with concomitant use of glucocorticoid, estrogen, and proton-pump inhibitor therapy.30 32 33 35
Evaluate patients who present with new thigh or groin pain for possibility of an atypical femoral fracture; include assessment of the contralateral limb.26 27 28 30 Consider interruption of bisphosphonate therapy in patients with manifestations of possible femoral fracture; weigh risks versus benefits of continued treatment.26 27 30 Discontinue if a femoral shaft fracture is confirmed.28 29 30
Although data are conflicting, possible increased risk of atrial fibrillation with use of bisphosphonates.21 22 23 24 FDA analysis of data from long-term (6 months to 3 years) controlled trials identified a higher rate of atrial fibrillation in patients receiving bisphosphonates (alendronate, ibandronate, risedronate, or zoledronic acid) versus placebo; however, only a few events reported in each study.23 FDA is continuing to monitor this safety concern.23
Potential Risk of Esophageal Cancer
Some evidence (from postmarketing experience and observational studies) suggests a possible association between use of oral bisphosphonates and an increased risk of esophageal cancer.25 36 37 However, because of conflicting data,37 38 39 additional study needed to confirm such findings.36
FDA states that benefits of oral bisphosphonates continue to outweigh their potential risks in patients with osteoporosis; it is important to consider that esophageal cancer is rare, especially in women.36 37
Avoidance of oral bisphosphonates in patients with Barrett’s esophagus, a known precursor to esophageal adenocarcinoma, has been recommended.25
Possible renal toxicity (e.g., deterioration of renal function and, rarely, renal failure) with bisphosphonates.7 12 Risk may be greater in patients with coexisting conditions associated with renal impairment, concomitant therapy with other nephrotoxic drugs, preexisting renal disease, dehydration, dosage, infusion volume and rate, and multiple cycles of treatment.4 7 8 9 10 11
Common Adverse Effects
Oral: Upper respiratory infection,1 back pain,1 dyspepsia,1 2 5 bronchitis,1 pain in the extremities,1 5 abdominal pain,1 diarrhea,1 5 headache,1 hypertension,1 pneumonia,1 myalgia,1 arthralgia,1 urinary tract infection,1 nausea.1
Interactions for Ibandronate Sodium
Antacids or Mineral Supplements Containing Divalent Cations
Pharmacokinetic interaction (decreased absorption of ibandronate) when tablets are used concomitantly with antacids or mineral supplements containing divalent cations (e.g., aluminum, calcium, magnesium, iron).1 5 44 Administer tablets ≥60 minutes prior to such drugs or supplements.1 5
Drugs Affecting Hepatic Microsomal Enzymes
Pharmacokinetic interactions unlikely.1
Drugs Excreted through Renal Tubular Transport
Specific Drugs and Tests
Histamine H2-receptor antagonists
Pharmacokinetic interaction unlikely with IV ibandronate7
No evidence of increased adverse upper GI effects1
Use concomitantly with caution1
Pharmacokinetic interaction unlikely with IV ibandronate7
Ibandronate Sodium Pharmacokinetics
Biochemical markers of bone turnover returned to baseline ≥12 months after treatment discontinuance.44
Bioavailability decreased by 90% when administered with a standard breakfast compared with administration under fasting conditions.1 Bioavailability and effect on BMD reduced when food and beverages taken <60 minutes following oral administration.1
In patients with renal impairment (Clcr 40–70 mL/minute), AUC is increased by 55% compared with that in patients with normal renal function (Clcr >90 mL/minute).7 Patients with severe renal impairment (Clcr <30 mL/minute) had >2-fold increase in AUC compared with exposure for healthy individuals.7 44
Plasma Protein Binding
Apparent oral terminal half-life is 37–157 hours; dose-dependent.1
Apparent IV terminal half-life is 4.6–25.5 hours; dose-dependent.7
25°C (may be exposed to 15–30°C).1
25°C (may be exposed to 15–30°C).7
For information on systemic interactions resulting from concomitant use, see Interactions.
Do not admix with calcium-containing solutions or other IV drugs.7
Advice to Patients
Importance of correct oral administration (e.g., avoiding foods and beverages other than plain water [including mineral water] prior to administration, not lying down for ≥60 minutes following administration).1 5 18 (See GI Effects under Cautions.)
Importance of discontinuing oral ibandronate and informing clinician if symptoms of esophageal disease (e.g., new or worsening dysphagia, difficulty or pain on swallowing, retrosternal pain, heartburn) develop.1 5
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (vitamins, supplements, antacids), as well as any concomitant illnesses (e.g., preexisting dysphagia, esophageal disorders, renal impairment).1 5 8
Importance of advising patients of other important precautionary information.1 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
2.5 mg (of ibandronate)
Boniva (with povidone)
Roche (also promoted by GlaxoSmithKline)
150 mg (of ibandronate)
Boniva (with povidone)
Roche (also promoted by GlaxoSmithKline)
Injection, for IV use only
1 mg (of ibandronate) per mL
Boniva (available in prefilled syringe with needle and swabs)
Roche (also promoted by GlaxoSmithKline)
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Boniva 150MG Tablets (GENENTECH): 1/$134.99 or 3/$387.98
Boniva 3MG/3ML Solution (GENENTECH): 3/$473.97 or 9/$1,340.03
AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions March 14, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. Roche Laboratories. Boniva (ibandronate sodium) tablets prescribing information. Nutley, NJ; 2011 Jan.
2. McClung MR, Wasnich RD, Recker R et al. Oral daily ibandronate prevents bone loss in early postmenopausal women without osteoporosis. J Bone Miner Res. 2004; 19:11-8. [PubMed 14753731]
3. Chesnut CH, Skag A, Christiansen C et al. Effect of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res. 2004; 19:1241-9. [PubMed 15231010]
4. Barrett J, Worth E, Bauss F et al. Ibandronate: a clinical pharmacological and pharmacokinetic update. J Clin Pharmacol. 2004; 44:951-65. [IDIS 519745] [PubMed 15317823]
5. Roche Laboratories. Boniva (ibadronate sodium) tablets patient information. Nutley, NJ; 2011 Jan.
6. National Osteoporosis Foundation. Physician’s guide to prevention and treatment of osteoporosis. Washington, DC; 2000. From National Osteoporosis Foundation website ().
7. Roche Pharmaceuticals. Boniva (ibandronate sodium) injection prescribing information. Nutley, NJ; 2011 May.
8. Roche Pharmaceuticals. Boniva (ibandronate sodium) injection patient information. Nutley, NJ; 2011 May.
9. Major P, Lortholary A, Han J et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol. 2001; 19:558-67. [IDIS 460631] [PubMed 11208851]
10. Brown DL, Robbins R. Developments in the therapeutic applications of bisphosphonates. J Clin Pharmacol. 1999; 39:651-60. [IDIS 430233] [PubMed 10392318]
11. Cheer SM, Noble S. Zoledronic acid. Drugs. 2001; 61:799-805. [PubMed 11398911]
12. Rosen LS, Gordon D, Kaminski M et al. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J. 2001; 7:377-87. [PubMed 11693896]
13. Migliorati CA, Casiglia J, Epstein J et al. Managing the care of patients with bisphosphonate-associated osteonecrosis: an American Academy of Oral Medicine position paper. J Am Dent Assoc. 2005; 136:1658-68. [PubMed 16383047]
14. Novartis. Zometa (zoledronic acid) injection prescribing information. East Hanover, NJ; 2005 Apr.
15. Reginster JY, Adami S, Lakatos P et al. Efficacy and tolerability of once-monthly oral ibandronate in postmenopausal osteoporosis: 2 year results from the MOBILE study. Ann Rheum Dis [serial online]. January 26, 2006. Available at .
16. Reginster JY. Oral and intravenous ibandronate in the management of postmenopausal osteoporosis: a comprehensive review. Curr Pharm Des. 2005; 11:3711-28. [PubMed 16305506]
17. Delmas PD, Adami S, Strugala C et al. Intravenous ibandronate injections in postmenopausal women with osteoporosis: one-year results form the dosing intravenous administration study. Arthritis Rheum. 2006; 54:1838-46. [PubMed 16729277]
18. Roche Pharmaceuticals, Nutley, NJ: Personal communication.
19. Center for Drug Evaluation and Research, Food and Drug Administration. FDA Alert: Information on bisphosphonates (marketed as Actonel, Actonel+Ca, Aredia, Boniva, Didronel, Fosamax, Fosamax+D, Reclast, Skelid, and Zometa. 2008 Jan 7. Available from FDA website. Accessed 2008 Oct 28.
20. Wysowski DK, Chang JT. Alendronate and risedronate: reports of severe bone, joint, and muscle pain. Arch Intern Med. 2005; 165:346-7. [PubMed 15710802]
21. Black DM, Delmas PD, Eastell R et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007; 356:1809-22. [PubMed 17476007]
22. Cummings SR, Schwartz AV, Black DM. Alendronate and atrial fibrillation. N Engl J Med. 2007; 356:1895-6. [PubMed 17476024]
23. Center for Drug Evaluation and Research, Food and Drug Administration. Update of safety review follow-up to the October 1, 2007 early communciation about the ongoing safety review of bisphosphonates. Bisphosphonates: alendronate (Fosamax, Fosamax plus D) etidronate (Didronel), ibandronate (Boniva), Pamidronate (Aredia), risedronate (Actonel, Actonel w/calcium), tiludronate (Skelid), and zoledronic acid (Reclast, Zometa). 2008 Nov 12. Available from FDA website. Accessed 2008 Nov 21.
24. Novartis. Zoledronic acid (Reclast) injection prescribing information. East Hanover, NJ. 2008 Jun.
25. Wysowski DK. Reports of esophageal cancer with oral bisphosphonate use. N Engl J Med. 2009; 360:89-90. Letter. [PubMed 19118315]
26. Food and Drug Administration. Boniva (ibandronate sodium) tablets [2010 Oct 13: Hoffman-LaRoche]. Safety labeling change and REMS notification. Silver Spring, MD; 2010 Oct 13). From FDA web site. ().
27. Food and Drug Administration. Boniva (ibandronate sodium) injection [2010 Oct 13: Hoffman-LaRoche]. Safety labeling change and REMS notification. Silver Spring, MD; 2010 Oct 13. From FDA web site. ().
28. Food and Drug Administration. FDA drug safety communication: Safety update for osteoporosis drugs, bisphosphonates, and atypical fractures. Silver Spring, MD; 2010 Oct 13. From FDA web site. (). Accessed 2010 Nov 4.
29. Food and Drug Administration. FDA MedWatch label change: Atypical fracture update for bisphosphonates (osteoporosis drugs) including alendronate (marketed as Fosamax), alendronate with cholecalciferol (marketed as Fosamax plus D), risedronate (marketed as Actonel and Atelvia), risedronate with calcium carbonate (marketed as Actonel with Calcium), ibandronate (marketed as Boniva), and zoledronic acid (marketed as Reclast). Silver Spring, MD; 2010 Oct 13. From FDA web site. (). Accessed 2010 Nov 4.
30. Shane E, Burr D, Ebeling PR et al. Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2010; 25:2267-94. [PubMed 20842676]
31. Food and Drug Administration. FDA News Release: Possible increased risk of thigh bone fracture with bisphosphonates. Silver Spring, MD; 2010 Oct 13. From FDA web site. (). Accessed 2010 Nov 4.
32. Giusti A, Hamdy NA, Papapoulos SE. Atypical fractures of the femur and bisphosphonate therapy: A systematic review of case/case series studies. Bone. 2010; 47:169-80. [PubMed 20493982]
33. Girgis CM, Sher D, Seibel MJ. Atypical femoral fractures and bisphosphonate use. N Engl J Med. 2010; 362:1848-9. [PubMed 20463351]
34. Sellmeyer DE. Atypical fractures as a potential complication of long-term bisphosphonate therapy. JAMA. 2010; 304:1480-4. [PubMed 20924014]
35. Schmidt GA, Horner KE, McDanel DL et al. Risks and benefits of long-term bisphosphonate therapy. Am J Health Syst Pharm. 2010; 67:994-1001. [PubMed 20516469]
36. Food and Drug Administration. FDA drug safety communication: Ongoing safety review of oral osteoporosis drugs (bisphosphonates) and potential increased risk of esophageal cancer. Rockville, MD; 2011 July 21. Available from FDA website. Accessed 2011 Sept 12.
37. Green J, Czanner G, Reeves G et al. Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: case-control analysis within a UK primary care cohort. BMJ. 2010; 341:c4444. [PubMed 20813820]
38. Cardwell CR, Abnet CC, Cantwell MM et al. Exposure to oral bisphosphonates and risk of esophageal cancer. JAMA. 2010; 304:657-63. [PubMed 20699457]
39. Abrahamsen B, Eiken P, Eastell R. More on reports of esophageal cancer with oral bisphosphonate use. N Engl J Med. 2009; 360:1789; author reply 1791-2.
40. Abrahamsen B, et al. The risk of oesophageal and cancer incidence and mortality in alendronate users: a national cohort study. Presented at the 3rd Joint Meeting of the European Calcified Tissue Society and the International Bone and Mineral Society. Athens, Greece: May 10, 2011. Abstract No. 0C29.
41. Solomon DH, Patrick A, Brookhart MA. More on reports of esophageal cancer with oral bisphosphonate use. N Engl J Med. 2009; 360:1789-90; author reply 1791-2. [PubMed 19391255]
42. Ross PD. Osteoporosis: frequency, consequences, and risk factors. Arch Intern Med. 1996; 156:1399-411. [IDIS 370197] [PubMed 8678708]
43. Eastell R. Treatment of postmenopausal osteoporosis. N Engl J Med. 1998; 338:736-46. [IDIS 402219] [PubMed 9494151]
44. Kehoe T, Colman E. Boniva (Ibandronate sodium) FDA approval package, Medical review. NDA No. 21-455. Rockville, MD; 2003 May 16.
More about ibandronate
- Ibandronate Sodium Injection (FDA)
- Ibandronate Sodium Tablets (FDA)
- Ibandronate Sodium (Wolters Kluwer)
- Other brands: Boniva