Fosamax/Fosamax Plus Special Precautions

General: To facilitate delivery to the stomach and thus reduce the potential for esophageal irritation, patients should be instructed to swallow each tablet of FOSAMAX/FOSAMAX PLUS with a full glass of water (200-250 mL) and not to lie down for at least 30 minutes and until after their first food of the day. Patients should not chew or suck on the tablet because of a potential for oropharyngeal ulceration. Patients should be specifically instructed not to take FOSAMAX/FOSAMAX PLUS at bedtime or before arising for the day. Patients should be informed that failure to follow these instructions may increase their risk of esophageal problems. Patients should be instructed that if they develop symptoms of esophageal disease (such as difficulty or pain upon swallowing, retrosternal pain or new or worsening heartburn) they should stop taking FOSAMAX/FOSAMAX PLUS immediately and consult their physician.
Causes of osteoporosis other than estrogen deficiency, aging and glucocorticoid use should be considered.
Osteonecrosis of the jaw: Osteonecrosis of the jaw (ONJ) has been reported in patients receiving treatment regimens including bisphosphonates. The majority of reports occurred following tooth extractions with delayed healing and involved cancer patients treated with intravenous bisphosphonates. Many of these patients were also receiving chemotherapy and corticosteroids. However, some cases have also occurred in patients receiving oral bisphosphonate treatment for postmenopausal osteoporosis and other diagnoses. The majority of reported cases have been associated with dental procedures such as tooth extraction. Many had signs of local infection, including osteomyelitis.
A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors. Known risk factors for osteonecrosis of the jaw include a diagnosis of cancer, concomitant therapies (e.g., chemotherapy, radiotherapy, corticosteroids, angiogenesis inhibitors, immunosuppressive drugs), poor oral hygiene, co-morbid disorders (e.g., periodontal and/or other pre-existing dental disease, anemia, coagulopathy, infection, diabetes mellitus), smoking, and heavy alcohol use.
Patients who develop osteonecrosis of the jaw should receive appropriate antibiotic therapy and/or oral surgery and discontinuation of bisphosphonate therapy should be considered based on individual benefit/risk assessment. Dental surgery may exacerbate the condition. For patients requiring dental procedures (e.g. tooth extraction, dental implants), there are no definitive data available to establish whether discontinuation of bisphosphonate treatment reduces the risk of ONJ.
Clinical judgment of the treating physician and/or oral surgeon should guide the management plan, including bisphosphonate treatment, of each patient based on individual benefit/risk assessment.
The following should be considered when evaluating a patient's risk of developing ONJ: Potency of the medicinal product that inhibits bone resorption (higher risk for highly potent compounds).
Route of administration (higher risk for parenteral administration).
Cumulative dose of bone resorption therapy.
Co-morbid conditions (e.g. anemia, coagulopathies) and smoking.
Periodontal disease, poorly fitting dentures, history of dental disease.
Osteonecrosis of the external auditory canal: Osteonecrosis of the external auditory canal has been reported with bisphosphonates, mainly in association with long-term therapy. Possible risk factors for osteonecrosis of the external auditory canal include steroid use and chemotherapy and/or local risk factors such as infection or trauma. The possibility of osteonecrosis of the external auditory canal should be considered in patients receiving bisphosphonates who present with ear symptoms including chronic ear infections.
Musculoskeletal: In post marketing experience, severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients taking bisphosphonates that are approved for the prevention and treatment of osteoporosis (see ADVERSE REACTIONS). However, such reports have been infrequent. This category of drugs includes FOSAMAX (alendronate sodium). Most of the patients were postmenopausal women. The time to onset of symptoms varied from one day to several months after starting the drug. Most patients had relief of symptoms after stopping the medication. A subset had recurrence of symptoms when rechallenged with the same drug or another bisphosphonate.
In placebo-controlled clinical studies of FOSAMAX, the percentages of patients with these symptoms were similar in the FOSAMAX and placebo groups.
Low-energy fractures of the subtrochanteric and proximal femoral shaft have been reported in some long-term (time to onset in the majority of reports ranged from 18 months to 10 years) alendronate-treated patients. Some were stress fractures (some of which were reported as insufficiency fractures) occurring in the absence of apparent trauma. Some patients experienced prodromal pain in the affected area, often associated with imaging features of stress fracture, weeks to months before a complete fracture occurred. Approximately one third of these fractures were bilateral; therefore the contralateral femur should be examined in patients who have sustained a femoral shaft stress fracture. Poor healing of these fractures was also reported. Patients with suspected stress fractures should be evaluated, including evaluation for causes and risk factors of stress fractures (e.g., vitamin D deficiency, malabsorption, glucocorticoid use, lower extremity arthritis or fracture, previous stress fracture, extreme or increased exercise, diabetes mellitus, chronic alcohol abuse), and receive appropriate orthopedic care. Interruption of alendronate therapy in patients with stress fractures should be considered based on individual benefit/risk assessment.
Endocrine and Metabolism: Hypocalcemia must be corrected before initiating therapy with FOSAMAX/FOSAMAX PLUS (see CONTRAINDICATIONS). Other disorders affecting mineral metabolism (such as vitamin D deficiency) should be treated. In patients with these conditions, serum calcium and symptoms of hypocalcemia should be monitored during therapy with FOSAMAX/FOSAMAX PLUS. Symptomatic hypocalcemia has been reported rarely, both in patients with predisposing conditions and patients without known predisposing conditions. Patients should be advised to report to their physicians any symptoms of hypocalcemia, such as paresthesias or muscle spasms. Physicians should carefully evaluate patients who develop hypocalcemia during therapy with FOSAMAX/FOSAMAX PLUS for predisposing conditions.
Due to the positive effects of alendronate in increasing bone mineral, small, asymptomatic decreases in serum calcium and phosphate may occur.
Fosamax Plus: Colecalciferol: FOSAMAX PLUS alone should not be used to treat vitamin D deficiency (commonly defined as 25-hydroxyvitamin D < 22.5 nmol/L or 9 ng/mL).
Patients suffering from osteoporosis are at an increased risk for vitamin D insufficiency, especially those over the age of 70 years, home bound, or chronically ill, and may need to receive vitamin D supplementation in addition to that provided in FOSAMAX PLUS (see Dosage & Administration).
Patients with gastrointestinal malabsorption syndromes may also require higher doses of vitamin D supplementation and measurement of 25-hydroxyvitamin D should be considered.
Vitamin D₃ supplementation may worsen hypercalcemia and/or hypercalciuria when administered to patients with diseases associated with unregulated overproduction of 1,25-dihydroxyvitamin D (e.g., leukemia, lymphoma, sarcoidosis). Urine and serum calcium should be monitored in these patients.
Gastrointestinal: FOSAMAX/FOSAMAX PLUS, like other bisphosphonates, may cause local irritation of the upper gastrointestinal mucosa.
Esophageal adverse experiences, such as esophagitis, esophageal ulcers and esophageal erosions, rarely followed by esophageal stricture or perforation, have been reported in patients receiving treatment with alendronate. In some cases these have been severe and required hospitalization. Physicians should therefore be alert to any signs or symptoms signaling a possible esophageal reaction and patients should be instructed to discontinue FOSAMAX/FOSAMAX PLUS immediately and seek medical attention if they develop dysphagia, odynophagia, retrosternal pain or new or worsening heartburn.
The risk of severe esophageal adverse experiences appears to be greater in patients who lie down after taking FOSAMAX/FOSAMAX PLUS and/or who fail to swallow it with a full glass (200-250 mL) of water, and/or who continue to take FOSAMAX/FOSAMAX PLUS after developing symptoms suggestive of esophageal irritation. Therefore, it is very important that the full dosing instructions are provided to, and understood by, the patient (see DOSAGE & ADMINISTRATION).
Because of possible irritant effects of alendronate on the upper gastrointestinal mucosa and a potential for worsening of the underlying disease, caution should be used when FOSAMAX/FOSAMAX PLUS is given to patients with active upper gastrointestinal problems, such as dysphagia, esophageal diseases (including known Barrett's esophagus), gastritis, duodenitis, or ulcers.
While no increased risk was observed in extensive clinical trials, there have been rare (post-marketing) reports of gastric and duodenal ulcers with alendronate, some severe and with complications.
Ophthalmologic: Ocular disturbances including conjunctivitis, uveitis, episcleritis and scleritis have been reported with alendronate therapy. Patients with ocular events other than uncomplicated conjunctivitis should be referred to an ophthalmologist for evaluation. If ocular inflammatory symptoms are observed, treatment may need to be discontinued.
Monitoring and Laboratory Tests: Not Applicable.
Special Populations: Use in Pregnancy: FOSAMAX/FOSAMAX PLUS has not been studied in pregnant women and should not be given to them.
Use in Lactation: FOSAMAX/FOSAMAX PLUS has not been studied in nursing mothers and should not be given to them.
Use in Children (<18 years of age): FOSAMAX/FOSAMAX PLUS has not been studied in patients <18 years of age and should not be given to them.
Use in Elderly (≥65 years of age): In clinical studies, there was no age-related difference in the efficacy or safety profiles of FOSAMAX.
Fosamax Plus: Colecalciferol: Daily requirements of vitamin D₃ may be increased in the elderly.