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Alendronate (Fosamax)

An oral bisphosphonate.

Pregnancy category AU: B3

Routes of administration oral

Bioavailability 0.6%

Metabolism excreted unchanged

Elimination half-life 126 months

Excretion Kidney

Alendronic acid, sold under the brand name Fosamax among others, is a bisphosphonate medication used to treat osteoporosis and Paget’s disease of bone.

Use is often recommended together with vitamin D, calcium supplementation, and lifestyle changes.

Common side effects include constipation, abdominal pain, nausea, and acid reflux.

Use is not recommended during pregnancy or in those with poor kidney function.

Alendronic acid works by decreasing the activity of cells that break down bone.

Alendronic acid 35 mg (as alendronate sodium 45.7 mg) oral tablet/

Recommended: 

Prevention 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

Acute inflammations of the gastrointestinal tract (esophagitis, gastritis, ulcerations).

Clinically manifested osteomalacia

Certain malformations and malfunctions of the esophagus (strictures, achalasia)

Inability to stand, walk, or sit for 30 minutes after oral administration

Renal impairment or chronic kidney disease as evidenced by a creatinine clearance below 30ml/min

Hypocalcemia

Pregnancy and breastfeeding

Side effects:

Gastrointestinal tract:

Ulceration and possible rupture of the esophagus.

Gastric and duodenal ulceration may also occur.

It is not associated with excess risk of esophageal cancer.

Infrequent cases of skin rash, rarely manifesting as Stevens–Johnson syndrome and toxic epidermal necrolysis, uveitis, scleritis and generalized muscle, joint, and bone pain, rarely severe have been reported. 

Osteonecrosis of the jaw may occur while on this drug.

Osteonecrosis risk is higher for extractions in the mandible than other areas of the mouth, and the risk increases if taking it for four or more years 

Osteonecrosis side effect is uncommon (0.4-1.6% for oral alendronic acid), it occurs primarily in patients being administered intravenous bisphosphonates, with most cases being reported in cancer patients.

Bone: alendronate has been linked in long-term users to the development of low-impact femoral fractures.

Alendronate have an increase in the numbers of osteoclasts and develop giant, more multinucleated osteoclasts.

Fosamax has been linked to subtrochanteric fractures.

Food and drugs containing large amounts of calcium, magnesium or aluminium antacids decrease the absorption of alendronate. 

At least half an hour should pass after intake of alendronate before eating dairy products or taking the supplement or drug.

Concomitant vitamin D treatment should be avoided.

Intravenous ranitidine increases the oral bioavailability of alendronate.

The combination of NSAIDs and alendronate may increase the risk of gastric ulcers. 

Both these drugs have the potential to irritate the upper gastro-intestinal mucosa.

Only oral bisphosphonate with reports of associated esophageal carcinoma, with a median time to diagnosis of 2.1 years.

Alendronate inhibits osteoclast-mediated bone-resorption. 

Alendronate specifically inhibits bone resorption without any effect on mineralization at pharmacologically achievable doses. 

Its inhibition of bone-resorption is dose-dependent and approximately 1,000 times stronger than the equimolar effect of the first bisphosphonate drug, etidronate. 

Alendronate is deposited in the bone-matrix in a pharmacologically inactive form. 

For optimal action alendronate  requires calcium and vitamin D are needed to promote normal bone development. 

Hypocalcemia should, be corrected before starting therapy.

The fraction of the drug that reaches the circulatory system intact after oral dosing is low, averaging only 0.6–0.7% in women and in men under fasting conditions. 

Intake together with meals and beverages other than water further reduces the bioavailability. 

The absorbed drug rapidly partitions, with approximately 50% binding to the exposed bone surface.

The remaining drug  is excreted unchanged by the kidneys. 

After absorption in the bone, alendronate has an estimated terminal elimination half-life of 10 years.

 

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