How common is it for patients to have difficulty tolerating oral bisphosphonates?
The difficulties with oral bisphosphonates became known from the original, daily, Alendronate (Fosamax) trials. During these trials, there appeared to be a higher incidence of gastrointestinal disorders. In 1996, post-marketing surveillance revealed a number of case reports of esophagitis (inflammation of the food pipe) and esophageal ulceration. According to the company, these were seen mostly in people who were not compliant with recommended dosing instructions (for example, patients were taking Alendronate with little or no water, taking it at bedtime and/or lying down within minutes after taking it, etc.). Several patients even continued taking Alendronate after the occurrence of symptoms suggestive of esophageal irritation. In a few cases, patients were found to have previously undiagnosed esophageal disorders. The recommendations from this discovery were to follow strict compliance with the dosing instructions, i.e. sitting up for 1/2 hour after the medication, and taking it on an empty stomach, first thing in the morning. These difficulties were not seen or reported with the weekly dosing of the drug.
These gastrointestinal findings were not seen with Residronate (Actonel) or Ibandronate (Boniva). The reason for this is not clear. It can possibly be explained by the different structure of the compounds and therefore improved tolerability or just due to the lack of reporting of a known side effect to another drug in the same class. The head to head FACT trial involving Residronate and Alendronate did not show any differences between the two drugs as far as tolerability.
In my practice, I find both of these drugs, as well as the newer bisphosphonate, extremely well-tolerated as a weekly or monthly medication.
At what point would a doctor consider intravenous administration?
Currently, there is only one FDA approved IV bisphosphonate, Boniva. It is given as a slow administration into a vein over 30 seconds. It is relatively painless and well-tolerated. In the future, there will likely be other drugs available. One such agent, zoledronic acid (Reclast), has shown notably significant data and will likely get approval soon. This will be available as a once yearly infusion. There is, however, some concern with this drug as it has shown considerable association, in specific populations, with osteonecrosis of the jaw (ONJ).
Due to the long-term experience, efficacy and tolerability of the oral agents, these should be used first. Only if one can not tolerate any of these, should one consider the use of an IV agent.
Published On: June 04, 2007