Last updated: October 22, 2014
Trade Names: Actonel
Drug Class: Bisphosphonate
Preparations: 5-, 30-, 35-, 75- , 150 mg tablets
Indications: Treatment and prevention of osteoporosis; treatment of Paget’s disease
Mechanism of Action: Antiresorptive; localizes to areas of bone resorption and inhibits osteoclast activity without any effect on bone formation; increases bone mineral density and significantly reduces fracture rates
Contraindications: Hypersensitivity, hypocalcemia, esophageal stricture or dysmotility; not recommended for patients with severe renal insufficiency (creatinine clearance <35 mL/min). Avoid use in patients who cannot stand or sit upright for 30 minutes after administration.
Precautions: If possible, avoid use if esophageal problems or renal impairment are present. Ensure that patient understands how the drug should be taken. A dental exam and preventive dental work should be performed before starting chronic bisphosphonate therapy.
Pregnancy Risk: C
Common: Mild GI disturbance (i.e., nausea, dyspepsia, dysphagia), hypocalcemia (transient, mild), headache
Uncommon: severe erosive esophagitis, atypical subtrochanteric femur fractures, osteonecrosis of the jaw, severe musculoskeletal pain, uveitis, altered taste, urticaria, angioedema, atrial fibrillation
Drug Interactions: GI adverse events are increased in patients taking NSAIDs
Patient Instructions: Take on an empty stomach (2 hours before meals). Should be taken with a full glass of water on arising in the morning. Nothing other than water should be taken for at least 30 minutes. Even coffee or fruit juice markedly reduce absorption. Delaying such intake for longer than 30 minutes (1–2 hours if possible) maximizes absorption. After taking, the patient must remain upright to reduce risk of esophageal irritation. Any other medications must be taken at least 30 minutes after bisphosphonate. Supplement calcium and vitamin D intake if needed.
Comments: Supplemental calcium and vitamin D are usually coadministered. Weekly or monthly dosing for osteoporosis is preferred.The optimal duration of treatment is uncertain. A temporary discontinuation may be considered after 3-5 years of therapy in patients at low risk of fracture with monitoring of bone density 2-3 years after discontinuation.
Clinical Pharmacology: Oral bioavailability is very poor (<1%) and negligible if administered with or after food. Absorbed drug is renally excreted and not metabolized. Terminal half-life exceeds 10 days, but elimination from body over months or years indicating localization and slow release from bone.
McClung M, Harris ST, Miller PD et al. Bisphosphonate therapy for osteoporosis: benefits, risks and drug holiday. Am J Med 2013;126:13-20. PMID: 23177553
Ralston SH. Clinical practice. Paget's disease of bone. N Engl J Med 2013;368:644-50.PMID: 23406029