Trip Answers

Question answered:18/12/07 Warning! this question is over two years old.

The SPC for Fosamax (once-weekly alendronate) contains a section on contraindications that includes:

 

“Abnormalities of the oesophagus and other factors which delay oesophageal emptying such as stricture or achalasia.”

 

Section 4.4 on special warnings and precautions for use advises:

 

“Alendronate can cause local irritation of the upper gastro-intestinal mucosa. Because there is a potential for worsening of the underlying disease, caution should be used when alendronate is given to patients with active upper gastro-intestinal problems, such as dysphagia, oesophageal disease, gastritis, duodenitis, ulcers, or with a recent history (within the previous year) of major gastro-intestinal disease such as peptic ulcer, or active gastro-intestinal bleeding, or surgery of the upper gastro-intestinal tract other than pyloroplasty (see 4.3 'Contra-indications').

 

Oesophageal reactions (sometimes severe and requiring hospitalisation), such as oesophagitis, oesophageal ulcers and oesophageal erosions, rarely followed by oesophageal stricture, have been reported in patients receiving alendronate. Physicians should therefore be alert to any signs or symptoms signalling a possible oesophageal reaction and patients should be instructed to discontinue alendronate and seek medical attention if they develop symptoms of oesophageal irritation such as dysphagia, pain on swallowing or retrosternal pain, new or worsening heartburn

 

The risk of severe oesophageal adverse experiences appears to be greater in patients who fail to take alendronate properly and/or who continue to take alendronate after developing symptoms suggestive of oesophageal irritation. It is very important that the full dosing instructions are provided to, and understood by the patient (see 4.2 'Posology and method of administration').” [1]

 

Similar information on contraindications and cautions are given in the CKS (formerly PRODIGY) guideline on osteoporosis. [2]

 

A 2002 guideline on the treatment of postmenopausal osteoporosis notes:

 

“The use of alendronate and risedronate has been associated with dyspepsia, abdominal pain and oesophageal ulceration and should be prescribed with caution in patients with a history of reflux oesophagitis or hiatus hernia. However, the overall risk of gastrointestinal events with alendronate and risedronate is very low (see Case history), and weekly bisphosphonates may further reduce the risk of this side effect.” [3]

 

Please note the above sources make no specific reference to the risk of gastrointestinal problems in patients with hiatus hernia taking a PPI in addition to alendronate. Similarly, we searched the TRIP and Medline databases but found no studies reporting the incidence of adverse events in this category of patients.

 

A case report, dating from 1998, describes oesophageal ulcer occurring in patient with a hiatus hernia taking alendronate . However, it is likely the patient was not taking a PPI in that it is not mentioned in the Medline abstract:

 

“OBJECTIVE: To describe a case of esophageal ulcer associated with the use of alendronate. CASE REPORT: This is the fifth case ever described in the literature according to our bibliographic review. In our patient, the association between the drug and the esophageal lesions was masked by the presence of a hiatal hernia, potentially a cause of the esophageal lesion. The persistence of the lesions despite high doses of anti-reflux therapy called attention to the possibility of the relationship. The esophageal lesion healed soon after suspension of alendronate. DISCUSSION: The authors present a review of the literature and point to the need for diagnostic investigation, to suspend such a drug from patients who experience dyspeptic symptoms while using it.” [4]

 

Given the little information on the risk of taking alendronate in patients with a hiatus hernia or a history of hiatus hernia, the NLH Primary Care Q & A Service would recommend contacting the pharmaceutical company for further assistance with this query:

 

Merck Sharp & Dohme Limited
Hertford Road
Hoddesdon
Hertfordshire
EN11 9BU

 

Telephone: +44 (0)1992 467 272

 

References
1. SPC for Fosamax Once Weekly 70mg tablets. November 2007. (http://emc.medicines.org.uk/emc/industry/default.asp?page=displaydoc.asp&documentid=4115)
2. CKS. Osteoporosis – treatment. May 2006.
(http://www.cks.library.nhs.uk/osteoporosis_treatment)
3. RACGP. Guidelines for the treatment of postmenopausal osteoporosis for general practitioners. http://www.racgp.org.au/Content/NavigationMenu/ClinicalResources/RACGPGuidelines/Osteoporosis/20021001guidelines_osteo.pdf
4. Ferrari Júnior AP and Domingues SH. Esophageal ulcer and alendronate. Sao Paulo Med J. 1998 Nov-Dec;116(6):1882-4. (http://www.hubmed.org/display.cgi?uids=10349198)

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