Stephen C. Piscitelli, PharmD

Disclosures

October 24, 2000

Question

A long-time HIV patient has an abnormal bone densitometry report reflecting osteopenia and had begun alendronate (Fosamax). The problem is that alendronate has specific restrictions about coadministration with foods and other medications, with the net result that the patient has stopped the alendronate. How important are the restrictions on alendronate -- such as recommendations about not lying down after taking the medication -- or other drug interactions? Are there alternative osteopenia agents that will be easier to coadminister with his HIV medications?

Response from Stephen C. Piscitelli, PharmD

Alendronate is an agent in the bisphosphonate class of drugs that alters bone remodeling and reduces bone resorption. When administered appropriately, alendronate is very well tolerated. However, there are important directions for its use, because it is highly irritating to the esophagus. Severe esophageal adverse effects have been noted, such as erosive esophagitis and esophageal ulcers. In 1996, postmarketing surveillance reported 1213 adverse effects received by the manufacturer.[1] Of these, 199 patients had esophageal adverse effects and 51 were described as serious or severe. A total of 16% of these patients were hospitalized. Where information was available, patients had not followed the directions for administration or had continued therapy even after developing upper gastrointestinal symptoms. This report only described those adverse effects reported to the manufacturer and may be an underestimate. Although there will clearly be interpatient variability with regard to susceptibility to side effects, these data emphasize the importance of proper administration.

To minimize these adverse effects, patients need to take the drug with 6-8 ounces of water to make sure the tablet passes into the stomach. It should also be taken on an empty stomach in the morning at least 30 minutes before the first food or beverage of the day to improve the absorption of the drug (waiting longer improves absorption). After dosing, the patient then needs to remain either sitting or standing for at least 30 minutes to avoid reflux of the drug into the esophagus. Due to the potential for serious adverse effects, the drug should be avoided in patients who are unable to remain upright for 30 minutes after dosing or those with esophageal abnormalities that delay gastric emptying. Patients should be counseled not to suck or chew the tablet. If the patient experiences dysphagia, odynophagia, or retrosternal pain, they should contact their physician and discontinue use. However, it should be noted that alendronate is now being studied -- and seems promising -- in a 40- to 70-mg once-weekly regimen.[2] This would eliminate many of the scheduling difficulties faced by HIV-infected patients.

The Food and Drug Administration recently approved risedronate (Actonel) for the treatment and prevention of postmenopausal osteoporosis and glucocorticoid-induced osteoporosis and treatment of Paget's disease. Risedronate was also well-tolerated in clinical trials, including patients with gastrointestinal disease such as ulcers, esophagitis, and heartburn, and those taking nonsteroidal anti-inflammatory drugs. However, due to the potential esophageal toxicity of this class of compounds, risedronate has the same directions and restrictions on its administration.

Options are indeed limited for patients with osteopenia. Patients should be receiving calcium supplements and vitamin D in combination with bisphosphonates. Intranasal calcitonin has also been used for this condition, although many patients find its tolerability unacceptable and response rates have been low.[3]

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