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Alendronate (Fosamax®, Merck) is a bisphosphonate drug used for osteoporosis and several other bone diseases. It is marketed alone as well as in combination with vitamin D (2,800 U, under the name Fosavance).
Pharmacokinetics
The systemic bioavailability after oral dosing is only 0.6 % as well in women and in men (fasting state). Intake together with meals and certain drinks (coffee, orange juice) further reduces the bioavailability. Soft tissues and bones are fastly reached by about 50%. After resorption in the bone alendronate has an estimated terminal halflife of 10 years; the remainder is excreted unchanged by the kidneys.
Pharmacology
Alendronate blocks osteoclast-mediated bone-resorption. It is chemically related to etidronate and the N-containing bisphosphonates such as pamidronate, which with it shares the same mode of action. Its inhibition of bone-resorption is dose-dependent and 100 to 1,000 times stronger than the equimolar effect of etidronate. Theoretically, alendronate may also inhibit bone-mineralization but this effect is 6,000 times weaker than the inhibition of bone-resorption. Under therapy normal bone tissue develops and alendronate is deposited in the bone-matrix in pharmacologically inactive form. For optimal action enough calcium and vitamin D are needed in the body. Hypocalcemia should therefore be corrected before starting therapy.
Uses
- Prophylaxis and treatment of female osteoporosis
- Treatment of male osteoporosis
- Prevention and treatment of corticosteroid-associated osteoporosis together with supplements of calcium and vitamin D
- Paget's disease
Contraindications and precautions
- Acute inflammations of the gastrointestinal tract (esophagitis, gastritis, ulcerations)
- Clinically manifest osteomalacia
- Certain malformations and malfunctions of the esophagus (strictures, achalasia)
- Unability to stand, walk, or sit for 30 minutes after oral administration
- Renal impairment with a creatinine clearance below 30ml/min
- Hypersensitivity to alendronate or another ingredient
- Hypocalcemia
- Pregnancy and breastfeeding
- Patients below 18 yrs. of age, because no clinical data exists
Side-effects
- GI tract: most prominent are harmless side effects such as mild nausea, dyspepsia, abdominal cramps, flatulence, diarrhea, or obstipation. A severe side effect is an ulceration of the esophagus caused by alendronate, which may require hospitalization and intensive treatment. Gastric and duodenal ulceration.
- General: infrequent cases of skin rash, rarely manifesting as Stevens-Johnson syndrome and toxic epidermal necrolysis, eye problems (uveitis, scleritis) and generalized muscle, joint, and bone pain (rarely severe) have been seen. In laboratory tests decreased calcium and phosphate values may be obtained but reflect action of the drug and are harmless.
- Osteonecrosis of the jaw, a recognised side-effect of bisphosphonates.
Interactions
- Milk, diet and drugs containing high amounts of calcium, magnesium or aluminium (antacids): the resorption of alendronate is decreased. At least half an hour should pass after intake of alendronate before taking the supplement or drug.
- Highly active vitamin D analogues or fluorides: no data is available. Concomitant treatment should be avoided.
- The additional beneficial effect of HRT (hormone replacement therapy) with estrogens/progestins or raloxifene in postmenopausal women remains to be elucidated, but no interactions have been seen. The combination is therefore possible.
- Intravenous ranitidine increases the oral bioavailability of alendronate. No clinical consequences are known.
- The combination of NSAIDS and alendroate increases the risk of gastric ulcers. Both these drugs have the potential to irritate the upper gastro-intestinal mucosa.
Dosage
- Prophylaxis of osteoporosis in women: 5-10mg daily or 35-70mg weekly.
- Therapy of osteoporosis in women and men : 10mg daily or 70mg weekly.
- Osteoporosis under corticosteroids: 5mg daily or 35mg weekly in men and premenopausal women or those receiving concomitant HRT. In postmenopausal women not receiving HRT the recommended dose is 10mg daily or 70mg weekly.
- Paget's Disease: 40mg daily for 6 months.
Dosage forms
- Fosamax® solution 70mg/75ml
- Fosamax® tabletts 5mg, 10mg, 35mg, 40mg, and 70mg
Patent Remarks (USA)
Its patent is set to expire in 2008 and Merck has lost a series of appeals to block a generic version of the drug from being certified by the US FDA.
External links
"Alendronate"