Actonel with Calcium Disease Interactions

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.

Elevated serum concentrations of calcium and phosphate can exceed the solubility level and result in calcium- phosphate precipitates that deposit in vascular and renal systems as well as other soft tissues of the body. Therapy with calcium should be administered with extreme caution in patients with hyperphosphatemia (hypoparathyroidism or severe renal impairment). Administration of oral calcium acetate or calcium carbonate, in addition to providing calcium, complexes phosphates within the GI tract. These complexes are eliminated in the feces. Clinical monitoring of serum calcium and phosphate concentrations is necessary.

Calcium is involved in cardiac muscle contraction and electrical impulse conduction. Therapy with calcium salt formulations (particularly IV) should be administered cautiously to patients with cardiac disease. Patients receiving cardiac glycosides and concomitant IV calcium may experience arrhythmias. Therapy with IV calcium should be administered slowly and at reduced dosages in patients with cardiac disease.

Calcium is absorbed from the intestinal tract by active transport and passive diffusion. Malabsorption syndromes (celiac disease, GI resection), deficiency of vitamin D, parathyroid hormone, or calcitonin, or an alkaline gastric pH (achlorhydria, carbonate or phosphate salts) can decrease the absorption of oral formulations of calcium. Calcium is available in oral and parenteral formulations.

Absorption of oral calcium formulations may be altered and elimination of calcium by the kidney decreased with renal impairment. Hyperphosphatemia occurs during renal failure. Calcium acetate or calcium carbonate, in addition to providing calcium, complexes phosphates within the GI tract. Calcium carbonate can partially correct metabolic acidosis associated with chronic renal failure. Clinical monitoring of renal function and serum calcium and phosphate concentrations is necessary.

Hypercalciuria, with or without hypercalcemia, may occasionally occur in patients with sarcoidosis. Elevated calcium levels may result from increased intestinal absorption of calcium, which is related to the extrarenal production of vitamin D by mononuclear phagocytes present within the sarcoid granuloma. Therapy with calcium salts should be administered cautiously and only if necessary in patients with sarcoidosis.

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.

Risedronate is primarily eliminated by the kidney. The renal clearance of the drug is decreased in patients with impaired renal function. Risedronate is not recommended for use in patients with creatinine clearance less than 30 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 >= 30 mL/min).