Bisphosphonate (anti-resorptive)
Alendronate is a medicine (bisphosphonate) used to treat and prevent osteoporosis, making bones stronger and reducing the risk of fractures. It is usually taken once a week, on an empty stomach, with a glass of water, and you must remain upright for at least 30 minutes afterwards.
Also known as: Fosamax, ácido alendrónico, alendronic acid, sodium alendronate
Bisphosphonate + NSAID: additive gastrointestinal risk.
Alendronate, like oral bisphosphonates, can irritate the esophageal and gastric mucosa, while ibuprofen inhibits gastroprotective prostaglandins (COX-1), increasing the risk of ulcer and bleeding. The combination potentiates the risk of upper gastrointestinal injury: esophagitis, peptic ulcer and bleeding, particularly in the elderly, in patients with a history of ulcer or with high NSAID doses. Take alendronate on an empty stomach with water (as per the dosing instructions), consider gastroprotection in at-risk patients and use the lowest effective ibuprofen dose for the shortest time, watching for symptoms such as epigastric pain, dysphagia and melaena.
Alendronate + ibuprofen: additive risk of upper gastrointestinal irritation and injury (esophagitis/ulcer). Use with caution, especially in the elderly and in patients with a history of ulcer.
Both may irritate the oesophagogastric mucosa.
GI symptoms (dyspepsia, pain, dysphagia).
Epigastric pain, dysphagia, melena.
Watch for GI symptoms; consider gastroprotection if risk factors exist.
DailyMed (FDA) — approved Alendronate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c7e470d6-508e-466e-a78d-060bbbc9745c ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=291602fa-8ebe-4200-bba7-9798c90f8a50 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Bisphosphonate + antacids: marked reduction of alendronate absorption.
Antacids containing calcium, magnesium or aluminium form insoluble chelates with oral bisphosphonates such as alendronate, markedly reducing their absorption and efficacy (risk of therapeutic failure in osteoporosis). Alendronate should be taken on an empty stomach, with water, at least 30 minutes before the first food or medicine of the day. When an antacid is needed, administration should be separated as much as possible (ideally 2 hours), and the patient should be instructed to keep the usual alendronate schedule so adherence is not compromised.
Alendronate + antacids: cations (calcium, magnesium, aluminium) chelate alendronate and reduce its absorption. Separate administration by at least 30 minutes, ideally 2 hours.
Calcium, aluminium and magnesium in antacids chelate alendronate in the GI tract, preventing absorption.
Confirm adherence to the correct dosing schedule.
Lack of therapeutic effect; persisting osteoporosis/bone pain.
Separate administration by at least 2 hours (alendronate on an empty stomach, with plain water).
DailyMed (FDA) — approved Alendronate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c7e470d6-508e-466e-a78d-060bbbc9745c ; approved Antacids label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5e346dc0-69ce-4cc5-bb5d-bfa833e11c1f — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Alendronate + calcium: calcium binds the bisphosphonate and prevents its absorption.
Alendronate and other oral bisphosphonates have a very low bioavailability that depends on being taken fasting, with plain water, and on having no food, drinks or other medicines in the stomach that can bind the drug. Calcium (and other cations) forms complexes with the bisphosphonate in the gastrointestinal tract, preventing its absorption and abolishing the antiresorptive effect. In practice, alendronate should be taken on waking, fasting, with a glass of water, waiting at least 30–60 minutes before eating or taking the calcium supplement (ideally calcium with the next meal).
Calcium + alendronate: calcium binds the bisphosphonate and prevents its absorption. Separate by ≥ 30–60 min (fasting).
Calcium salts form insoluble complexes with alendronate in the stomach.
Adherence and response to osteoporosis therapy.
Lack of efficacy (fractures), no other acute symptoms.
Take alendronate 30-60 minutes before calcium, in the morning on an empty stomach.
DailyMed (FDA) — approved Alendronate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ffdd2496-d253-419b-85a6-8c615f7545f1 ; approved Calcium carbonate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=348d3dfa-6a52-4583-96e3-83c4bf2df45b — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Bisphosphonate + PPI: possible reduced alendronate absorption and effect.
Omeprazole reduces gastric acidity, which can decrease the absorption of some oral bisphosphonates and their efficacy in osteoporosis; additionally, long-term proton pump inhibitor use is associated with an increased risk of bone fractures (possibly through reduced calcium absorption and direct effects on bone metabolism). In patients taking alendronate, the PPI should be used only with a clear indication, at the lowest dose and for the shortest time possible; reassess the need for gastroprotection and ensure adequate calcium and vitamin D intake.
Omeprazole + alendronate: PPIs can reduce bisphosphonate absorption and long-term use is associated with a higher fracture risk. Reassess the PPI need.
Acid suppression may reduce alendronate dissolution/absorption.
Assess adherence and therapeutic response.
Fracture or lack of densitometric improvement.
Ensure correct schedule (fasting + water) and reassess the need for the PPI.
DailyMed (FDA) — approved Alendronate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c7e470d6-508e-466e-a78d-060bbbc9745c ; approved Omeprazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6ea9a6f3-b756-4cdf-b3db-f666a2c17d66 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Food, especially calcium-rich food, markedly reduces absorption.
Take alendronate fasting (on waking) with plain water and do not eat for 30-60 min.
EMC-UK (MHRA) — approved Alendronate SmPC: https://www.medicines.org.uk/emc/product/5206/smpc
Calcium in dairy binds alendronate and prevents its absorption.
Do not take with milk, yoghurt or dairy; take alendronate on an empty stomach with plain water and wait 30-60 min.
EMC-UK (MHRA) — approved Alendronate SmPC: https://www.medicines.org.uk/emc/product/5206/smpc
Alendronate is not recommended with creatinine clearance < 35 mL/min.
Contraindicated; consider an alternative.
EMC-UK (MHRA) — approved Alendronate SmPC: https://www.medicines.org.uk/emc/product/5206/smpc
Alendronate should only be used once calcium is corrected.
Correct hypocalcaemia and vitamin D deficiency before starting.
EMC-UK (MHRA) — approved Alendronate SmPC: https://www.medicines.org.uk/emc/product/5206/smpc
Alendronate may cause severe oesophagitis; contraindicated in oesophageal abnormalities delaying transit.
Contraindicated in stricture/achalasia and swallowing difficulty.
EMC-UK (MHRA) — approved Alendronate SmPC: https://www.medicines.org.uk/emc/product/5206/smpc
Bisphosphonates are not recommended in pregnancy (long half-life and bone deposition).
Avoid in pregnancy; discontinue before planned conception if clinically possible.
Unknown; prefer to avoid during breastfeeding.
Discontinue before planned pregnancy; use effective contraception.
EMC-UK (MHRA) — approved Alendronate SmPC: https://www.medicines.org.uk/emc/product/5206/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Antiresorptive bisphosphonate: binds to bone hydroxyapatite and specifically inhibits the activity of osteoclasts, the bone-resorbing cells. Reduces bone turnover (the number of sites at which bone is remodelled), with formation exceeding resorption, leading to progressive gains in bone mass. Daily oral doses of 5–40 mg produce biochemical changes indicative of dose-dependent inhibition of resorption (decreased urinary calcium and collagen degradation markers).
At the cellular level, alendronate localises preferentially to sites of bone resorption, under the osteoclasts. The osteoclasts adhere normally to the bone surface but lack the ruffled border indicative of active resorption — alendronate does not interfere with osteoclast recruitment or attachment, but inhibits their activity. Alendronate incorporated into the bone matrix is not pharmacologically active, so it must be administered continuously.
Mean oral bioavailability is only 0.64% (women) and 0.59% (men) when administered after an overnight fast and 2 hours before a standardised breakfast. Bioavailability decreases by approximately 40% when given 0.5 or 1 hour before breakfast, and is negligible with or up to 2 hours after a meal. Coffee and orange juice reduce it by about 60%. Plasma protein binding is ~78%.
There is no evidence that alendronate is metabolised in animals or humans. Excretion is renal: after a single intravenous 14C-alendronate dose, approximately 50% of the radioactivity was excreted in the urine within 72 hours and little or none in the faeces. Renal clearance was 71 mL/min and systemic clearance did not exceed 200 mL/min.
The terminal half-life in humans is estimated to exceed 10 years, probably reflecting release of alendronate from the skeleton. Plasma concentrations after therapeutic oral doses are too low (<5 ng/mL) for analytical detection. After 10 years of oral treatment (10 mg/day), the amount released daily from the skeleton is estimated at ~25% of that absorbed.
