Alendronate

Class

Indications

    • Treatment and prevention of osteoporosis in women

    • Paget's disease of bone

    • To reduce hypercalcemia in tumor-induced bone disease

Administration/Absorption

    • Mean oral bioavailability of alendronate in women was 0.7%

Dosage

    • Prophylaxis of osteoporosis in women: 5–10 mg daily or 35–70 mg weekly

    • Paget's Disease: 40 mg daily for 6 months

Distribution

    • 78% protein bound

    • VOD 28 L

Mechanism

    • Based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone

    • Also targets farnesyl pyrophosphate (FPP) synthase

      • Acts as a analogue 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)

        • Essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins

      • This activity inhibits osteoclast activity and reduces bone resorption and turnover

Excretion

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

    • Approximately 50% excreted in the urine within 72 hours

Side effects

    • Can damage the esophagus

      • By toxicity from the medication itself

      • Also by nonspecific irritation secondary to contact between the pill and the esophageal mucosa

    • Rash

Interactions

    • Milk, diet, and drugs containing high amounts of calcium, magnesium or aluminium decrease absorption

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

Contraindications

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

    • Clinically manifest osteomalacia

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

    • Inability 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, as no clinical data exists