Generic Name: Alendronate (no generic available, U.S. patent expires August 2012)
Common Brand Name: Fosamax (Merck & Company – U.S.)
Popularity: 29th most commonly prescribed drug between 2002-2009 (U.S.)
Class: Calcium regulator (bisphosphonate)
Treatment Uses
For prevention and treatment of postmenopausal osteoporosis (women), treatment of osteoporosis in men, and treatment of steroid induced osteoporosis in men and women. Treatment of Paget’s disease.
Has been used for treatment of osteoporosis associated with Crohn’s disease and for hypercalcemia caused by malignancies (cancerous tumors). Alendronate has been used to increase bone mineral density (BMD) around the knee following total knee replacement and in treatment of avascular necrosis of the femoral head (hip), both with good results.
Use of alendronate to alleviate regional pain associated with reflex sympathetic dystrophy syndrome may possibly be helpful. Osteoporosis related to Crohn’s Disease and male hypogonadism seems to improve with alendronate as does low bone density associated with Cystic Fibrosis. Fibrous bone dysplasia seems to improve with alendronate as does osteoporosis secondary to growth hormone deficiency and juvenile idiopathic generalized osteoporosis.
Alendronate has been used to successfully treat vitamin D intoxication (overdose) caused hypercalcemia in infants. Alendronate has not been effective in treating osteogenesis imperfecta.
Osteoporosis is a condition characterized by low bone density or mass, leading to fractures. It is most often seen in women after menopause when new bone formation is less than bone resorption (breakdown). Fractures of the spine, hip, and wrist often result, especially in women aged 50 and older.
A significant cause of osteoporosis is dietary deficiency of calcium and/or vitamin D. Patients should achieve minimum daily recommended quantities of both calcium and vitamin D using supplements, if necessary, before starting alendronate.
Weight bearing exercises are also beneficial along with modification of health risk factors such as smoking cessation and reducing excessive alcohol consumption. When calcium supplements are used, timing is important: the presence of calcium in the stomach significantly reduces the alendronate absorption.
Dosing and administration
The recommended dose of alendronate for postmenopausal osteoporosis and osteoporosis in men is 10 milligrams 10 milligrams orally, taken each morning, or (preferentially), 70 milligrams once a week. For prophylaxis against osteoporosis in women or for treatment of steroid induced osteoporosis in adults, the recommended dose is 5 milligrams orally each morning or 35 milligrams once each week. Alendronate is not recommended for use in children; dosing information is not available. An intravenous form of alendronate is available.
Alendronate should be taken in the morning immediately after rising, not at bedtime or before getting out of bed for the day. Alendronate tablets should be taken with a full glass (6 to 8 ounces) of water and oral solution with at least 2 ounces (a quarter of a cup) of water, 30 minutes or less before eating food, drinking other beverages, or taking other medications – waiting more than 30 minutes improves absorption of alendronate, but the benefit may not be clinically significant.
Food, beverages (other than water), and other meds taken within 30 minutes of alendronate reduce absorption and therapeutic effects of alendronate. Patients should not lie down for at least 30 minutes after taking oral alendronate. Bioavailability of alendronate is reduced by 40 percent when taken within one hour of eating breakfast as compared to taking within two hours of eating breakfast. Coffee and orange juice reduces alendronate absorption by 60 percent and should not be consumed with alendronate tablets.
Dosage adjustments are not needed in patients with renal insufficiency unless their creatinine clearance is less than 35 milliliters per minute, in which case alendronate is not recommended for use. Dose adjustments are not necessary in older patients or persons with liver dysfunction or failure.
Lethal doses in humans are unknown. Rats and mice died following single oral doses ranging from 552 to 1280 milligrams per kilogram. Doses of up to 200 milligrams per kilogram were not fatal to dogs. The most common symptoms believed to result from an overdose would be upset stomach, heartburn, esophagitis, gastritis, or ulceration.
There would also be significant hypocalemia and hypophosphatemia. Milk or antacids should be given to bind the alendronate and providers should assure the patient remains fully upright. Do not induce vomiting. Dialysis would not be helpful.
Pharmacology/pharmacokinetics/stability
Following oral administration, initial response to alendronate occurs in an average of one month with a range of three to six months and may take as long as six to 12 months. Following discontinuation of alendronate, biochemical changes return to baseline in about three weeks.
Alendronate is not metabolized. Nearly half (50 percent) is excreted by the kidneys, representing the proportion not retained in bones.
The safety of alendronate in pregnant women is questionable. Used primarily in post-menopausal women, alendronate is stored in bone for long periods of time. Animal studies suggest that fetal bone uptake of alendronate is greater than maternal bone.
Studies have also shown alendronate to cross the placenta into fetuses, inducing adverse effects. Given these data, alendronate should be avoided during pregnancy. It is unknown whether alendronate is excreted in breast milk. If so, direct harmful effects to nursing infants would not be expected. Nonetheless, caution is advised when breastfeeding.
Alendronate binds to bone and inhibits the action of osteoclasts (bone-resorbing cells, responsible for demineralization). Preventing loss of calcium minerals slows osteoporotic changes.
Alendronate comes in 5, 10, 35, 40, and 70 milligram white colored oral tablets which vary in size and shape by dose. They should not be broken, crushed or chewed. It also comes in a clear, colorless oral solution with a raspberry flavor. Alendronate tablets should be stored between 59 and 86 F. Oral solution should be stored at room temperature (77 F), with excursions permitted between 59 to 86 F.
Cautions and warnings
Alendronate is extremely caustic and can damage the esophagus if regurgitated or not passed into the stomach when swallowed. Patients with esophageal disease, significant reflux, Barrett’s esophagitis, gastritis, ulcers, or esophageal strictures should not take alendronate.
This also applies to patients who cannot sit upright for 30 minutes after taking alendronate and patients with significant risk for aspiration. Alendronate has been associated with atypical femoral shaft fractures and osteonecrosis of the jaw and should be discontinued in any patients at risk or evidencing such pathologies.
Weekly dosing of alendronate is preferential to lessen the likelihood of esophageal damage (by lowering the administration frequency). No differences in effectiveness have been seen between daily and weekly administrations; substantial decreases in esophageal injury are noted with weekly dosing.
Patients should understand that failing to follow proper administration instructions will increase their risk of esophageal problems. They should also be instructed to stop taking alendronate and consult their health care provider if they develop symptoms of esophageal problems such as difficult or painful swallowing, new or increased heartburn, or chest pain.
Bone mineral density (BMD) should be measured at the initiation of alendronate therapy and at six to 12 month intervals thereafter.
Important side effects and interactions
Gastrointestinal side effects were the most commonly reported in patients taking alendronate although their incidence in both large and small studies did not vary significantly from patients taking placebo, ranging from 1 percent to 5 percent. While uncommon, severe musculoskeletal pain has been reported with alendronate, sometimes occurring years into therapy; discontinuation is recommended.
Currently, there are 12 drugs reported to interact with alendronate. Of these, none are significant to prehospital and emergency medicine providers although it is worthwhile to be aware that alendronate has a high affinity for calcium as well as other multivalent cations.
Many antacids contain calcium, magnesium, or aluminum, which bind with alendronate, reducing absorption in the gut. To prevent this, calcium, magnesium, or aluminum-containing antacids should be administered at least 30 minutes after alendronate. Calcium containing foods such as dairy products have like effects.
Average Costs – U.S.
• 10 mg/70mg tablet (generic)*
Patient cost: $1.58/7.42 each
Large Hospital cost: $0.15/0.75 each
*Wal Mart® and Target supply alendronate 70 mg and 35 mg tablets at $9 for 4 tablets (30 day supply) or $24 for 12 tablets (90 day supply)
References
1. MICROMEDEX® Healthcare Series: Thomson Micromedex, Greenwood Village, Colorado (accessed January, 2011).
2. Albany Medical Center Pharmacy, Albany, New York.
