Alendronate

From Anvita Health Wiki

Contents 1 Introduction 2 Indications 3 Contraindications 4 Dosage 5 Pharmacokinetics 6 Monitor 7 Adverse-effects 8 Drug-interactions 9 Mechanism-of-action 10 Clinical-trials 11 More General Terms 12 Additional Terms 13 Internet Database 14 References

Introduction

• Tradename: Fosamax.

Indications

• osteoporosis* & osteopenia [12]

• post- menopausal women
• chronic glucocorticoid use, i.e. COPD
• androgen-deprivation therapy for prostate cancer

• Paget's disease

• * Limit therapy to 5 years (see bisphosphonate)

Contraindications

• hypocalcemia: must be corrected prior to initiation of alendronate therapy
• delayed esophageal emptying

• stricture
• achalasia

• inability to stand or sit upright for at least 30 minutes after each dose
• hypersensitivity to bisphosphonates
• do NOT give to patients with creatinine clearance < 35 mL/min [10]
  

• pregnancy category = c
• safety in lactation = -

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
• long-term effects not known
• concurrent hormone replacement in postmenopausal women is not recommended

• 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]
• no data to support continued bisphosphonate therapy > 5 years for risk reduction of hip fracture [21]

• 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]
• Not covered by MediCal

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

• Ca+2
• phosphate
• Mg+2
• K+
• creatinine

• 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]

• overdose: hypocalcemina, hypophosphatemia
• other

• inhibition of bone turnover & bone repair, resulting in atypical fractures [13,19]
• atrial fibrillation ? [18]

• * may be less frequent with weekly 70 mg dose [7, 8]
  

• drug adverse effects of bisphosphonates

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

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]

More General Terms

• bisphosphonate

Additional Terms

• Fosamax Actonel Comparison Trial
• hypercalcemia
• osteopenia
• osteoporosis

Internet Database

PubChem: 2088
PubChem: 60736
PubChem: 62958

References

1. Pharmacy Phacts Vol. 12 #2, Valley Medical Center, Fresno CA
2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
4. Journal Watch 20(3):21, 2000
5. Raven et al Ann Intern Med 131:935, 1999
6. Prescriber's Letter 7(11):62 2000
7. Journal Watch 22(5):38, 2002 Lanza et al, Am J Gastroenterol 97:58, 2002
8. 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. Prescriber's Letter 10(5):26 2003
10. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
11. Bone HG et al, 10 years experienced with alendronate for osteoporosis in postmenopausal women, N Engl J Med 350:1189, 2004 PMID: [1]
12. 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: [2]
13. 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: [3]
    - Ott SM. Long-term safety of bisphosphonates. J Clin Endocrinol Metab. 2005 Mar;90(3):1897-9. PMID: [4]
14. UpToDate 13.3 [5]
15. 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: [6]
    - Prescriber's Letter 14(2): 2007 Length of bisphosphonate therapy Detail-Document#: [7] (subscription needed) [8]
16. Greenspan SL et al, Effect of once-weeklys oral alendronate on bone loss in men receiving androgen deprivation therapy for prostate cancer. A randomized trial. Ann Intern Med 2007, 146:416 PMID: [9]
17. Prescriber's Letter 14(6): 2007 New Developments With Bisphosphonate Therapy Detail-Document#: [10] (subscription needed) [11]
18. 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: [12]
19. 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: &dopt=Abstract
    - 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: [13]
20. Abrahamsen B et al Proton pump inhibitor use and the antifracture efficacy of alendronate. Arch Intern Med 2011 Jun 13; 171:998. PMID: [14]
21. Whitaker M et al Bisphosphonates for Osteoporosis — Where Do We Go from Here? N Engl J Med 2012 May 9, <PubMed> PMID: [15] <Internet> [16]
    - Black DM et al Continuing Bisphosphonate Treatment for Osteoporosis — For Whom and for How Long? N Engl J Med 2012 May 9, <PubMed> PMID: [17] <Internet> [18]

alendronate (Fosamax, Fosamax Plus D)