sunlight (UV) exposure
Fosamax Contraindications and Precautions
A history of GI disease is an independent risk factor for the development of GI adverse reactions during alendronate therapy. Severe reactions requiring hospitalization have occurred. Alendronate should be used with caution in patients with esophageal and GI disease, including dysphagia, esophagitis, gastritis, gastroesophageal reflux disease (GERD), hiatal hernia, duodenitis, ulcers, or GI perforation. Alendronate is contraindicated in patients with abnormalities of the esophagus which delay esophageal emptying such as esophageal stricture or achalasia. Patients who can not remain sitting or standing upright for at least 30 minutes after taking alendronate should not receive the medication. Prescribers and health care professionals should closely monitor patients for any signs or symptoms an esophageal reaction. Patients should be counseled to discontinue alendronate and seek medical attention if they develop dysphagia, odynophagia, or retrosternal pain. The risk of esophageal reactions increases in patients who do not follow the administration instructions. It is very important that patients understand and follow these instructions.
Elderly patients may be at increased risk for the development of adverse GI reactions during alendronate therapy. Increased age has been identified as an independent risk factor particularly for GI perforations, ulcers, or bleeding, but not necessarily esophageal events.
Preexistent hypocalcemia must be corrected before initiating alendronate therapy. Similarly, vitamin D deficiency must also be corrected. Adequate intake of calcium and vitamin D during treatment are essential. This is most important for patients with Paget’s disease who are to receive alendronate. Alendronate can decrease serum calcium and phosphate in these patients, who may have a higher rate of bone turnover.
About 50% of a single IV dose of alendronate is excreted in the urine. Studies in animals indicated that any alendronate not deposited in bone was rapidly excreted. Renal failure in animals led to increased amounts of alendronate in plasma, kidney, spleen, and tibia. No human study results are available, but it is likely that patients with severe renal impairment will accumulate alendronate. No dosage adjustment is recommended by the manufacturer if creatinine clearance is > 35 ml/min (mild to moderate renal insufficiency). Until further evidence is available alendronate is not recommended for patients with creatinine clearance < 35 ml/min (renal failure).
Alendronate is not indicated for use in children. Bisphosphonates have been used successfully in children for treatment of specific disease states (i.e., hypercalcemia of malignancy, idiopathic or glucocorticoid induced osteoporosis, osteogenesis imperfecta, Paget’s disease). The efficacy and safety of alendronate in children aged 4 - 18 years of age with osteogenesis imperfecta has been evaluated. In a 2-year study, 109 patients were randomized to either 5 mg of alendronate once daily (weight < 40 kg) or 10 mg of alendronate once daily (weight >= 40 kg), and 30 patients were randomized to placebo. The mean change in BMD Z-score from baseline was 1.3 in the alendronate-treated groups and 0.1 in the placebo group; treatment with alendronate did not reduce fracture rates. Of the patients who sustained a radiologically-confirmed fracture by month 12 of the study, 16% of alendronate-treated compared with only 9% of placebo-treated patients had delayed fracture healing or fracture non-union when assessed radiographically at month 24. In addition, at month 24, patients treated with alendronate demonstrated decreased bone turnover and delayed mineralization time. There were no differences between the alendronate-treated and the placebo-treated patients with respect to bone pain. Extreme caution must be used to ensure appropriate use in children; excessive doses of bisphosphonates may compromise skeletal quality during growth, despite concomitant increases in bone density. In a case report, inappropriate and excessive doses of pamidronate in a child resulted in osteopetrosis (abnormally dense and misshapen bone predisposed to fracture). It may be advisable to monitor biochemical markers of skeletal turnover when bisphosphonates are used in children to help assure clinicians that skeletal resorption is not excessively suppressed.
The risk versus benefit of alendronate therapy in patients who are receiving systemic prednisone doses < 7.5 mg/day (or other corticosteroid equivalent) has not been established. Before initiating therapy, the hormonal status of both men and women should be determined and appropriate replacement therapy started if needed. Bone mineral density measurements should be done at baseline and after 6 - 12 months of combined corticosteroid and alendronate therapy. The efficacy of alendronate in the treatment of corticosteroid-induced osteoporosis has been shown in patients with a median bone mineral density that is 1.2 standard deviations below the mean for healthy young adults.
Alendronate is classified as FDA pregnancy risk category C. After a bisphosphonate is incorporated into bone matrix it is gradually released from the bone over a period of weeks to years. The extent of bisphosphonate incorporation into adult bone, and hence, the amount available for release back into systemic circulation, is directly related to the total dose and duration of bisphosphonate use. Although there are no data on fetal risk in humans, bisphosphonates do cause fetal harm in animals, suggesting the uptake of bisphosphonates into fetal bone is greater than into maternal bone, and animal reproductive studies indicate alendronate, in particular, may induce fetal skeletal changes and decrease in serum calcium, as well as possibly effect fetal viability. Therefore, there is a theoretical risk of fetal harm if a woman becomes pregnant during or after completing a course of bisphosphonate therapy. The impact of variables such as time between cessation of bisphosphonate therapy to conception, the particular bisphosphonate used, and the route of administration on this risk has not been established. Because of the potential for adverse effects of bisphosphonates in the developing fetus, alendronate should only be used in pregnancy if the potential benefit justifies any possible risk to the mother and fetus.
In animals, IV alendronate is excreted into milk. Human studies have not been undertaken, but alendronate should not be given to breast-feeding women.
Alendronate should be used cautiously in patients with known phosphonate hypersensitivity.
Sunlight (UV) exposure should be limited in patients receiving alendronate. Alendronate may cause a rash that is worsened by exposure to the sun.
Osteonecrosis of the jaw has been reported in patients with cancer receiving treatment regimens and bisphosphonates (most commonly pamidronate and zoledronic acid), but also occasionally in patients receiving chronic oral bisphosphonate therapy for osteoporosis. In patients with cancer receiving intravenous bisphosphonates, many patients were also receiving chemotherapy and corticosteroids. The majority of reported cases have been associated with dental procedures for dental disease, such as tooth extraction, and many of these patients had signs of local infection including osteomyelitis; however, cases have appeared spontaneously. It would be prudent for patients with concomitant risk factors (e.g. cancer, chemotherapy, corticosteroid therapy, dental disease, or poor oral hygiene) to consider receiving a dental examination with appropriate preventive dentistry prior to treatment. Invasive dental procedures should be avoided, if possible, during treatment. If osteonecrosis of the jaw does develop during bisphosphonate therapy, it should be noted that dental surgery may exacerbate the condition. For patients requiring dental work, no data are available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. The treating physician and dentist should use their best clinical judgment to guide the management plan of each patient based on individual benefit and risk assessments.
[ Last revised: 1/16/2006 5:45:00 PM ]
References
. Bauer DC, Black D, Ensrud K , et al. Upper gastrointestinal tract safety profile of alendronate: The Fracture Intervention Trial. Arch Intern Med 2000;160:517 - 525.
. Whyte MP, Wenkert D, Clements KL, et al. Bisphosphonate-induced osteopetrosis. N Engl J Med 2003;349:457 - 63.
. Ruggiero SL, Mehrotra B, Rosenberg TJ, et al. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 2004;62:527 - 34.
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