alendronate (Fosamax, Fosamax Plus D, Binosto)
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Introduction
Tradename: Fosamax.
Indications
- osteoporosis & osteopenia[12]
- post-menopausal women
- chronic glucocorticoid use, i.e. COPD
- hypogonadism
- Paget's disease of the bone
Contraindications
- hypocalcemia: must be corrected prior to initiation of alendronate therapy
- delayed esophageal emptying
- inability to stand or sit upright for at least 30 minutes after each dose
- hypersensitivity to bisphosphonates
- renal failure
- do NOT give to patients with creatinine clearance < 35 mL/min[10][31][32][34]
- severe renal impairment[33]
- esophagitis, including history of esophagits associated with GERD treated with omeprazole[30]
- vitamin D deficiency
Benefit/risk
- number needed to treat
- 38 patients with >= 5 years of alendronate therapy would need to be treated for an additional 5 years to prevent 1 hip fracture[28]
- number needed to harm
- 183 patients for 4 years to precipitate 1 case of osteonecrosis of the jaw[25]
- 1449 patients with >= 5 years of alendronate therapy would need to be treated for an additional 5 years to cause 1 subtrochanteric/femoral shaft fracture[28]
Dosage
- Paget's disease: 40 mg QD for 6 months.
- supplemental calcium & vitamin D if indicated
- monitor alkaline phosphatase post-therapy for relapse
- osteoporosis: 10 mg PO QD or 70 mg PO weekly
- life-long therapy indicated (controversial, see bisphosphonate)
- 10 years of therapy if prior pathologic fracture[35]
- long-term effects not known
- concurrent hormone replacement in postmenopausal women is not recommended
- life-long therapy indicated (controversial, see bisphosphonate)
- must be taken at least 30 minutes before 1st food, beverage or medication of the day
- patient must avoid lying down for at least 30 minutes after administration
- for many women, discontinuation after 5 years of therapy does not significantly increase fracture risk[15]
- risk of vertebral fractures may be diminished with continuation of bisphosphonate therapy > 5 years[21][29]
- no data to support continued bisphosphonate therapy > 5 years for risk reduction of hip fracture[21][29]
- benefit/risk ratio remains favorable for > 10 years in postmenopausal women with osteoporosis[28]
- age & lower bone mineral density at the time of discontinuation of alendronate predict fracture risk[23]
Tabs: 10 & 40 mg.
Weekly tabs 35 mg & 70 mg. (packets of 4)
Foxamax + D, 70 mg + 2800 IU or 5600 IU vitamin D3[17]
Binosto: effervescent tab for oral solution; 70 mg weekly[22]
Not covered by MediCal
* correct vitamin D deficiency prior to administration for osteoporosis
Pharmacokinetics
- poorly absorbed orally, 1-5% of oral dose
- food interferes with absorption
- plasma 1/2life of 1 hour
- eliminated in urine (80%), not metabolized
- 20% of absorbed dose taken up by bone
- bisphosphonate may persist in bone for lifetime
elimination via liver
elimination via kidney
Monitor
- serum chemistries
- serum Ca+2
- serum phosphate
- serum Mg+2
- serum K+
- serum creatinine (see contraindications above)
- serum cystatin C/creatine ratio more accurately assesses renal function (not directly affected by muscle mass)[35]
- complete blood count (CBC) with differential
- bone densitometry
- biochemical markers of bone turnover
- serum osteocalcin
- urinary N-telopeptide cross-links (OsteoMark)
Adverse effects
- most commmon (1-10%)
- headache
- musculoskeletal pain
- flatulence
- gastroesophageal reflux (GERD)
- esophagitis* (especially when supine post administration)
- ulcer
- dysphagia
- abdominal distention & pain
- uncommon (< 1%)
- rash, erythema (rare), gastritis
- ocular inflammation:
- conjunctivitis, blurred vision, eye pain (rare)[9]
- osteonecrosis of the jaw[25]
- 0.23% after 2 years; 0.92% after 10 years
- advanced age, drug duration, & coexisting diabetes & rheumatoid arthritis are contributing factors[25]
- overdose: hypocalcemina, hypophosphatemia
- other
- inhibition of bone turnover & bone repair, resulting in atypical fractures[13][19], risk increases > 5 years use
- > 70% of patients with weight-bearing pain prior to atypical fracture
- atrial fibrillation ?[18]
- inhibition of bone turnover & bone repair, resulting in atypical fractures[13][19], risk increases > 5 years use
* may be less frequent with weekly 70 mg dose [7, 8]
Drug interactions
- ranitidine: doubles alendronate bioavailability
- aspirin: increased risk of GI side effects
- antacids: decreased absorption of alendronate
- proton pump inhibitors may blunt the beneficial effect of bisphosphonates to prevent hip fractures in the elderly (> 70 years of age)[20]
- drug interaction(s) of bisphosphonates with proton pump inhibitors
- drug interaction(s) of bisphosphonate with Ca+2
Mechanism of action
- bisphosphonates act primarily on bone to inhibit bone resorption by blocking osteoclastic activity
- diminishes risk of secondary hip fractures, vertebral fractures & other factures [26, 27]
- diminishes risk of primary vertebral fractures[27]
Clinical trials
- hormone replacement more effective than alendronate for increasing bone mineral density in post menopausal women[4][5]
- with alendronate bone mineral density is maintained or increased over 10 years of use[11]
- 2 year gains are nearly all lost after 2 years off of alendronate[4][5]; 5 year gains are at least partially retained 5 years later[11]
- 70 mg PO weekly did not cause esophagitis over 10 weeks[7]
- reduces vertebral fractures in patients with osteopenia at the femoral neck[12]
- does not reduced risk of breast cancer
More general terms
Additional terms
Component of
References
- ↑ Pharmacy Phacts Vol. 12 #2, Valley Medical Center, Fresno CA
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ 4.0 4.1 4.2 Journal Watch 20(3):21, 2000
- ↑ 5.0 5.1 5.2 Raven et al Ann Intern Med 131:935, 1999
- ↑ Prescriber's Letter 7(11):62 2000
- ↑ 7.0 7.1 Journal Watch 22(5):38, 2002 Lanza et al, Am J Gastroenterol 97:58, 2002
- ↑ Journal Watch 22(23):173-74, 2002 Greenspan S et al, Mayo Clin Proc 77:1044, 2002 Cryer B & Bauer DC, May Clin Proc 77:1031, 2002
- ↑ 9.0 9.1 Prescriber's Letter 10(5):26 2003
- ↑ 10.0 10.1 Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
- ↑ 11.0 11.1 11.2 Bone HG et al, 10 years experienced with alendronate for osteoporosis in postmenopausal women, N Engl J Med 350:1189, 2004 PMID: https://www.ncbi.nlm.nih.gov/pubmed/15028823
- ↑ 12.0 12.1 12.2 Journal Watch 25(8):64-65, 2005 Quandt SA, Thompson DE, Schneider DL, Nevitt MC, Black DM; Fracture Intervention Trial Research Group. Effect of alendronate on vertebral fracture risk in women with bone mineral density T scores of-1.6 to -2.5 at the femoral neck: the Fracture Intervention Trial. Mayo Clin Proc. 2005 Mar;80(3):343-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15757015
- ↑ 13.0 13.1 Journal Watch 25(9):69, 2005 Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CY. Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab. 2005 Mar;90(3):1294-301. Epub 2004 Dec 14. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15598694
Ott SM. Long-term safety of bisphosphonates. J Clin Endocrinol Metab. 2005 Mar;90(3):1897-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15758064 - ↑ UpToDate 13.3 http://www.utdol.com
- ↑ 15.0 15.1 Black DM et al, Effects of continuing or stopping alendronate after 5 years of treatment. The Fracture Intervention Trial Long-term Extension (FLEX). A randomized trial. JAMA 2006, 296:2927 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17190893
Prescriber's Letter 14(2): 2007 Length of bisphosphonate therapy Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=230203&pb=PRL (subscription needed) http://www.prescribersletter.com - ↑ Greenspan SL et al, Effect of once-weekly oral alendronate on bone loss in men receiving androgen deprivation therapy for prostate cancer. A randomized trial. Ann Intern Med 2007, 146:416 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17371886
- ↑ 17.0 17.1 Prescriber's Letter 14(6): 2007 New Developments With Bisphosphonate Therapy Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=230613&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 18.0 18.1 Heckbert SR, Li G, Cummings SR, Smith NL, Psaty BM. Use of alendronate and risk of incident atrial fibrillation in women. Arch Intern Med. 2008 Apr 28;168(8):826-31. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18443257
- ↑ 19.0 19.1 Capeci CM and Tejwani NC. Bilateral low-energy simultaneous or sequential femoral fractures in patients on long-term alendronate therapy. J Bone Joint Surg Am 2009 Nov; 91:2556. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19884427
Lenart BA et al. Association of low-energy femoral fractures with prolonged bisphosphonate use: A case control study. Osteoporos Int 2009 Aug; 20:1353. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19066707 - ↑ 20.0 20.1 Abrahamsen B et al Proton pump inhibitor use and the antifracture efficacy of alendronate. Arch Intern Med 2011 Jun 13; 171:998. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21321287
- ↑ 21.0 21.1 21.2 Whitaker M et al Bisphosphonates for Osteoporosis - Where Do We Go from Here? N Engl J Med 2012 May 9, <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22571168 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMp1202619
Black DM et al Continuing Bisphosphonate Treatment for Osteoporosis - For Whom and for How Long? N Engl J Med 2012 May 9, <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22571169 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMp1202623 - ↑ 22.0 22.1 Prescriber's Letter 20(1): 2013 Binosto: Alendronate Effervescent Tablet for Oral Solution Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=290105&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 23.0 23.1 Bauer DC et al. Fracture prediction after discontinuation of 4 to 5 years of alendronate therapy: The FLEX study. JAMA Intern Med 2014 May 5 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24798675
- ↑ Hue TF, Cummings SR, Cauley JA et al Effect of Bisphosphonate Use on Risk of Postmenopausal Breast Cancer. Results From the Randomized Clinical Trials of Alendronate and Zoledronic Acid. JAMA Intern Med. Published online August 11, 2014. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25111880 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=1893923
- ↑ 25.0 25.1 25.2 25.3 Chiu W-Y et al. The risk of osteonecrosis of the jaws in Taiwanese osteoporotic patients treated with oral alendronate or raloxifene. J Clin Endocrinol Metab 2014 Aug; 99:2729. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24758181
- ↑ Reid IR Efficacy, effectiveness and side effects of medications used to prevent fractures. J Intern Med. 2015 Jun;277(6):690-706 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25495429
- ↑ 27.0 27.1 Wells GA, Cranney A, Peterson J, et al. Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database System Rev. 2008; Issue 1, No: CD001155 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18253985
- ↑ 28.0 28.1 28.2 28.3 Abrahamsen B, Eiken P, Prieto-Alhambra D, Eastell R. Risk of hip, subtrochanteric, and femoral shaft fractures among mid and long term users of alendronate: nationwide cohort and nested case-control study. BMJ 2016;353:i3365 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27353596 <Internet> http://www.bmj.com/content/353/bmj.i3365
- ↑ 29.0 29.1 29.2 Medical Knowledge Self Assessment Program (MKSAP) 18, American College of Physicians, Philadelphia 2018
- ↑ 30.0 30.1 Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022 - ↑ 31.0 31.1 PDR Prescriber's Digital Reference https://www.pdr.net/drug-summary/Fosamax-alendronate-sodium-352.4609#10
- ↑ 32.0 32.1 alendronate (Rx) https://reference.medscape.com/drug/fosamax-binosto-alendronate-342810
- ↑ 33.0 33.1 Wilkens Parker LR, Preuss CV Alendronate StatPearls. 2022. March 31 https://www.ncbi.nlm.nih.gov/books/NBK526073/
- ↑ 34.0 34.1 NEJM Knowledge+
- ↑ 35.0 35.1 35.2 An JN, Kim JK, Lee HS, Kim SG, Kim HJ, Song YR. Serum cystatin C to creatinine ratio is associated with sarcopenia in non-dialysis-dependent chronic kidney disease. Kidney Res Clin Pract. 2022 Sep;41(5):580-590. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35791742 PMCID: PMC9576455 Free PMC article.
- ↑ HIGHLIGHTS OF PRESCRIBING INFORMATION FOSAMAX (alendronate sodium) tablets, for oral use https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021575s017lbl.pdf