Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alendronate is an aminobisphosphonate which appears to attenuate, rather than completely inhibiting bone turnover, by suppressing the activity of osteoclasts. Clinical trials have established that 10 mg/day orally administered alendronate is the optimum dosage. Despite its poor bioavailability after oral administration, alendronate is highly effective at preventing bone loss associated with the absence of endogenous estrogen. A sustained increase in bone mass was observed during alendronate therapy without accelerated loss after withdrawal of the drug. Increased bone mass was associated with a reduction in the risk and rate of occurrence of vertebral fractures. A recent study demonstrated a 47% reduction in the risk of developing new radiographic vertebral fractures over 3 years in women with low bone mass and pre-existing vertebral fractures. There have been few direct comparisons in clinical trials. However, when compared with calcium or low dosages of salmon calcitonin (salcatonin) therapy in women with postmenopausal osteoporosis, alendronate induced a sustained increase in bone mass during therapy that was not seen with the comparator. In clinical trials alendronate was generally well tolerated when taken as recommended. Adverse events tended to be transient and usually associated with the upper gastrointestinal tract; the most common events included abdominal pain, nausea, dyspepsia, constipation and diarrhoea, which are also common with other bisphosphonates. Of potential concern are the small number of reports of patients developing oesophageal ulceration; however, this adverse event was attributed to noncompliance with the manufacturer's recommendations for administration of the drug. In addition, alendronate has not been associated with osteomalacia. Studies are still required to establish the long term efficacy of alendronate, particularly with regard to other available therapies. Although estrogen replacement therapy is generally considered the treatment of choice for the management of postmenopausal osteoporosis, many women are unable or unwilling to receive estrogens on a long term basis. Thus, alendronate, with its demonstrated beneficial effects and its good tolerability profile (when taken as recommended), is a promising alternative treatment option for the management of postmenopausal osteoporosis.
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PMID:Alendronate. A review of its pharmacological properties and therapeutic efficacy in postmenopausal osteoporosis. 907 43

Alendronate is indicated for the treatment of osteoporosis in post-menopausal women. Although the drug has been associated with reports of severe oesophagitis, there have been no studies establishing the incidence of such reactions. Information was collected on 1523 patients included in a study conducted by means of prescription-event monitoring. Dyspepsia, nausea/vomiting, and abdominal pain were the most frequently reported events in the first month of treatment. After follow-up, 20 patients (1.3%) experienced oesophageal events that were considered to be possibly related to alendronate.
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PMID:United Kingdom experience with alendronate and oesophageal reactions. 966 93

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