indication

For the treatment and prevention of osteoporosis in women and Paget's disease of bone in both men and women.

pharmacology

Alendronate, a second-generation bisphosphonate is the first member of a group of drugs which strengthens bone. Alendronate is used to reduce hypercalcemia in tumor-induced bone disease, to treat corticosteroid-induced osteoporosis and Paget's disease, and to prevent osteoporosis in postmenopausal women.

mechanism of action

The action of Alendronate on bone tissue is based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone. Alendronate also targets farnesyl pyrophosphate (FPP) synthase. Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins. This activity inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass.

toxicity

Alendronate can damage the esophagus both by toxicity from the medication itself and by nonspecific irritation secondary to contact between the pill and the esophageal mucosa, similar to other cases of "pill esophagitis."

biotransformation

There is no evidence that alendronate is metabolized in humans or animals.

absorption

Relative to an intravenous (IV) reference dose, the mean oral bioavailability of alendronate in women was 0.7% for doses ranging from 5 to 40 mg when administered after an overnight fast and two hours before a standardized breakfast. Oral bioavailability of the 10 mg tablet in men (0.59%) was similar to that in women (0.78%) when administered after an overnight fast and 2 hours before breakfast.

half life

>10 years

route of elimination

Following a single IV dose of [14C]alendronate, approximately 50% of the radioactivity was excreted in the urine within 72 hours and little or no radioactivity was recovered in the feces.

drug interactions

Calcium: Formation of non-absorbable complexes

Calcium Acetate: Calcium Salts may decrease the serum concentration of Bisphosphonate Derivatives such as alendronate. Avoid administration of oral calcium supplements within 30 minutes after alendronate.

Calcium Chloride: Calcium salts may decrease the serum concentration of bisphosphonate derivatives. Avoid administration of oral calcium supplements within 30 minutes after alendronate/risedronate.

Diclofenac: Increased risk of gastric toxicity

Diflunisal: Increased risk of gastric toxicity

Etodolac: Increased risk of gastric toxicity

Fenoprofen: Increased risk of gastric toxicity

Flurbiprofen: Increased risk of gastric toxicity

Ibuprofen: Increased risk of gastric toxicity

Indomethacin: Increased risk of gastric toxicity

Iron Dextran: Formation of non-absorbable complexes

Ketorolac: Increased risk of gasrtic toxicity

Magnesium: Formation of non-absorbable complexes

Mefenamic acid: Increased risk of gastric toxicity

Nabumetone: Increased risk of gastric toxicity

Naproxen: Increased risk of gastric toxicity

Oxaprozin: Increased risk of gastric toxicity

Oxyphenbutazone: Increased risk of gastric toxicity

Piroxicam: Increased risk of gastric toxicity

Tenoxicam: Increased risk of gastric toxicity