Alendronate/cholecalciferol Disease Interactions

The manufacturer considers the use of alendronate sodium oral solution to be contraindicated in patients at increased risk of aspiration.

Osteonecrosis of the jaw (ONJ), which can occur spontaneously, is generally associated with tooth extraction and/or local infection with delayed healing, and has been reported in patients taking bisphosphonates. Known risk factors for osteonecrosis of the jaw include invasive dental procedures (e.g., tooth extraction, dental implants, boney surgery), diagnosis of cancer, concomitant therapies (e.g., chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, and co-morbid disorders (e.g., periodontal and/or other pre-existing dental disease, anemia, coagulopathy, infection, ill-fitting dentures). The manufacturers of bisphosphonates recommend discontinuation of bisphosphonate treatment for patients undergoing invasive dental procedures. Patients who develop osteonecrosis of the jaw while on bisphosphonate therapy should receive care by an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition. Discontinuation of bisphosphonate therapy should be considered based on individual benefit/risk assessment.

The use of bisphosphonates is contraindicated for the treatment of osteoporosis in patients with hypocalcemia. These agents increase bone mineral density, a process that requires an adequate supply of calcium in the body. Following the initiation of therapy, a short-term reduction in serum calcium and phosphate levels usually occurs due to inhibition of bone resorption, especially in patients with Paget's disease, in whom the pretreatment rate of bone turnover may be greatly elevated. Hypocalcemia and other disturbances of mineral metabolism, such as vitamin D deficiency, should be treated prior to initiation of therapy. Appropriate intake of calcium and vitamin D should be ensured throughout the course of treatment.

Bisphosphonates may cause local irritation of the upper gastrointestinal mucosa. Esophagitis and esophageal ulcers and erosions, occasionally with bleeding, as well as gastric and duodenal ulcers, have been reported, primarily with alendronate. Because of their structural similarities, therapy with all bisphosphonates should be administered cautiously in patients with active upper gastrointestinal disorders. The usual precautions should be followed closely to minimize the risk of irritation (i.e. taking the medication with a full glass of water after arising for the day and remaining upright for at least 30 minutes afterwards and until the first food intake of the day). Therapy should be discontinued if dysphagia, odynophagia or retrosternal pain occurs. The manufacturer of alendronate considers its use to be contraindicated in patients with abnormalities of the esophagus that may delay esophageal emptying, such as stricture or achalasia.

Vitamin D analogs function to increase serum calcium concentrations and can exacerbate arrhythmias, particularly in patients receiving cardiac glycosides. Therapy with vitamin D analogs should be administered cautiously in patients with or predisposed to cardiac arrhythmias. Clinical monitoring of serum electrolyte concentrations and cardiac function is recommended.

Vitamin D analogs administered in the presence of hyperphosphatemia can result in precipitation of calcium-phosphate deposits within the vascular or renal systems or other soft tissue calcifications. A solubility product (Serum Calcium X Phosphate) should not exceed 70. Serum electrolyte concentrations should be corrected prior to vitamin D analog therapy and monitored during therapy.

Vitamin D analogs such as calciferol and ergocalciferol should not be given to patients with hypercalcemia, malabsorption syndrome, or evidence of vitamin D toxicity.

Ergocalciferol, cholecalciferol, and calcifediol undergo renal biotransformation during metabolic activation. Renal impairment can alter metabolic and therapeutic activity of certain vitamin D analogs. Alternative vitamin D analogs such as dihydrotachysterol (hepatic activation) and calcitriol (active form) may be considered in patients with compromised renal function.

Each tablet of Binosto (alendronate effervescent) contains 650 mg sodium, equivalent to 1650 mg NaCl. Use caution in patients on sodium restriction, such as patients with a history of heart failure, hypertension, or other cardiovascular diseases.

Alendronate is primarily eliminated by the kidney. In healthy controls, drug that is not deposited in bone is rapidly excreted in the urine. Although clinical information is not available, animal studies suggest reduced drug clearance in renal failure. Alendronate is not recommended for use in patients with creatinine clearance less than 35 mL/min due to a lack of clinical experience in this setting. No dosage adjustment is necessary in patients with mild to moderate renal impairment (CrCl >= 35 mL/min).

There have been reports of bronchoconstriction in aspirin-sensitive patients receiving bisphosphonates. Use of these agents in asthmatic and in aspirin-sensitive patients should be used with caution.

Vitamin D analogs are fat soluble and oral formulations require bile for adequate intestinal absorption. Hepatic and/or biliary dysfunction decrease the absorption of vitamin D analogs. Metabolites of vitamin D analogs are primarily excreted in bile and feces. Ergocalciferol, cholecalciferol, and dihydrotachysterol undergo hepatic hydroxylation during metabolic activation. Hepatic impairment can alter the metabolic and therapeutic activity of certain vitamin D analogs. Alternative vitamin D analogs such as calcifediol (requires renal activation) and calcitriol (active form) may be considered in patients with compromised hepatic function.