Brands, Medical Use, Clinical Data
Drug Category
- Antiresorptives
- Bisphosphonates
- Antihypocalcemic Agents
Dosage Forms
- Tablets (6.53, 13.05, 45.68, 52.21 or 91.37 mg of alendronate monosodium salt trihydrate)
Brands / Synonyms
Acide Alendronique [Inn-French]; Acido Alendronico [Inn-Spanish]; Acidum Alendronicum [Inn-Latin]; Adronat; Alendronate; Alendronate Sodium; Alendronic acid; Alendros; Arendal; Binosto; Fosamax; Fosamax Plus D; Onclast
Indications
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.
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.
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."
Biotrnasformation / Drug Metabolism
There is no evidence that alendronate is metabolized in humans or animals.
Contraindications
· Abnormalities of the esophagus which delay esophageal emptying such as
stricture or achalasia
· Inability to stand or sit upright for at least 30 minutes
· Patients at increased risk of aspiration should not receive FOSAMAX oral
solution.
· Hypersensitivity to any component of this product
· Hypocalcemia
Drug Interactions
Intravenous ranitidine was shown to double the bioavailability of oral alendronate.
The clinical significance of this increased bioavailability and
whether similar increases will occur in patients given oral H2-antagonists
is unknown; no other specific drug interaction studies were performed.
Products containing calcium and other multivalent cations likely will interfere
with absorption of alendronate.
|
