Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011168 (dysphagia)
 15,644 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The bisphosphonate, alendronate sodium (e.g. Fosamax) is a bone resorption inhibitor used to treat postmenopausal osteoporotic women and osseous Paget's disease. Esophagitis is one of the adverse effects (AE) associated to its use. Five (5) patients with alendronate-associated esophagitis assisted in the Gastroenterologic Center, Rosario, Argentina, between October 1996 and December 1999 are described. The aim is to correlate the clinical, endoscopic and histopathological findings in 5 women (ages 57-71) complaining for upper digestive symptoms (dysphagia, epigastralgia, retrosternal pain.). All had osteoporosis treated with alendronate 10 mg/day and received detailed instructions about how to take the medication. The time from the beginning of alendronate intake and the appearance of the symptoms was elapsed 30, 35, 67, 85 and 90 days. The esophagitis was graded according to the Savary-Miller Classification. The videoscopy disclosed esophagitis of III and IV grades. Three patients had also antral and antroduodenal lesions, one of them associated to Helicobacter Pylori. Anatomopathologic findings confirm esophagitis and esophagic ulceration. Some authors claim that bisphosphonates as a new class of gastrotoxic drugs with AE similar to aspirin. Even when it is administrated according to the instructions of the manufacturers it should be used with caution. Our contribution emphasize the importance of this AE and suggest measures to diminish or suppress them, and take into consideration those patients who are taking aspirin. With alendronate, as well as with other potentially corrosive agents, is very important to take in mind the measures to prevent AE.
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PMID:[Esophagitis associated with use of alendronate in 5 postmenopausic patients]. 1147 18

Alendronate is a potent bisphosphonate that is effective in preventing osteoporotic fractures. Clinical trial data involving over 17,000 women provide a large, placebo-controlled experience from which alendronate has been demonstrated to be safe and well tolerated. We review the safety profile of alendronate in the context of its pharmacology, preclinical information and published literature on bisphosphonates. The clinical data include information from 1) the two primary Phase III osteoporosis treatment studies involving 994 women with postmenopausal osteoporosis treated with alendronate for up to 3 years; 2) upper gastrointestinal (GI) tolerability data (including special subgroup analyses) from the Fracture Intervention Trial (FIT), involving 2027 women with prior vertebral fractures; 3) an endoscopy study, and 4) postmarketing experience. Because all bisphosphonates have the potential to irritate the upper GI mucosa, we specifically investigated the safety and tolerability profile with respect to the upper GI tract. In the Phase III trials, alendronate 5 or 10 mg/day was well tolerated, with no increase relative to placebo in the incidence of overall adverse experiences (ie, inclusive of all events, not just those related to the GI tract). In the Phase III trials, alendronate 5 mg/day or 10 mg/day was well tolerated, with no increase relative to placebo in the incidence of overall adverse experiences. The incidence of upper gastrointestinal adverse experiences, overall, was similar among alendronate 5 mg or 10 mg and placebo, with abdominal pain and dysphagia being the only individual adverse experiences that were significantly increased (with alendronate 10 mg). Esophageal adverse experiences were uncommon, being reported in 8 (2.0%) patients receiving placebo and 9 (4.6%) patients taking alendronate 10 mg. None of the events occuring on alendronate therapy were serious or resulted in discontinuation. Tolerability was not affected by a wide range of concomitant medications including nonsteroidal anti-inflammatory drugs. Additional analyses of the 2027 postmenopausal women with vertebral fractures enrolled in FIT demonstrated that alendronate use was not associated with a significant increase in upper GI events, esophageal events, or gastroduodenal adverse events, even among women at high risk for upper GI complications (those older than 75 yr, those with previous upper GI disease, or those using NSAIDs). Esophageal adverse experiences (including esophagitis and esophageal ulcers) have been reported with alendronate in postmarketed use. A high proportion of these reports involved patients who did not follow the dosing instructions and probably relate to the irritant potential of refluxed gastric acid containing alendronate. Consistent with the antiresorptive mechanism of action of alendronate, asymptomatic decreases in serum calcium and phosphate were observed with alendronate treatment in the clinical trials. There were no other laboratory changes noted with alendronate. Now marketed in 78 countries and used by over 3 million women, the safety profile of alendronate, when dosed appropriately, has been consistent with that of the clinical trial experience. In view of the increased morbidity and mortality associated with fractures, and the proven efficacy of alendronate to reduce fracture risk, the benefit/risk ratio of alendronate remains highly favourable.
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PMID:The clinical tolerability profile of alendronate. 1266 41

Osteoporosis is a growing public health problem and several drugs have been developed in the past two decades to offer pharmacological solutions both in prevention and in therapy. Alendronate was the first compound registered as an anti-fracture agent and also the most prescribed drug worldwide for osteoporosis. Patient compliance is a major problem with alendronate, with studies demonstrating that 50-60% of patients discontinue treatment within one year. Dysphagia and swallowing difficulties are common especially among elderly people and the perceived potential for upper GI problems is a barrier to good long-term adherence. As non-persistence and non-compliance are linked to increased risk of fractures, efforts have been made to develop forms of alendronate which are more acceptable to patients. Among these, the drinkable formulations have the potential great convenience, simplicity of administration and reduction in gastro-intestinal side effects. In addition these novel soluble products are equivalent in cost to generic alendronate tablets. The approaches to improve adherence to an old and effective medication for osteoporotic patients will be reviewed in this report, with a special focus on the recently marketed product Bonasol 70 mg oral solution.
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PMID:A drinkable formulation of alendronate: potential to increase compliance and decrease upper GI irritation. 2455 29