Alendronic acid

Alendronate is a bisphosphonate that binds to bone hydroxyapatite and specifically inhibits the activity of osteoclasts, the bone-resorbing cells. Alendronate reduces bone resorption with no direct effect on bone formation, although the latter process is ultimately reduced because bone resorption and formation are coupled during bone turnover.

Animal studies have indicated the following mode of action. At the cellular level, alendronate shows preferential localization to sites of bone resorption, specifically under osteoclasts. The osteoclasts adhere normally to the bone surface but lack the ruffled border that is indicative of active resorption. Alendronate does not interfere with osteoclast recruitment or attachment, but it does inhibit osteoclast activity. Studies in mice on the localization of radioactive [3H] alendronate in bone showed about 10-fold higher uptake on osteoclast surfaces than on osteoblast surfaces. Bones examined 6 and 49 days after [3H] alendronate administration in rats and mice, respectively, showed that normal bone was formed on top of the alendronate, which was incorporated inside the matrix. While incorporated in bone matrix, alendronate is not pharmacologically active. Thus, alendronate must be continuously administered to suppress osteoclasts on newly formed resorption surfaces. Histomorphometry in baboons and rats showed that alendronate treatment reduces bone turnover (i.e., the number of sites at which bone is remodeled). In addition, bone formation exceeds bone resorption at these remodeling sites, leading to progressive gains in bone mass.

Treatment of Osteoporosis in Postmenopausal Women: The recommended dosage is one 70 mg tablet once weekly or one bottle of 70 mg oral solution once weekly or one 10 mg tablet once daily.

Prevention of Osteoporosis in Postmenopausal Women: The recommended dosage is one 35 mg tablet once weekly or one 5 mg tablet once daily.

Treatment to Increase Bone Mass in Men with Osteoporosis: The recommended dosage is one 70 mg tablet once weekly or one bottle of 70 mg oral solution once weekly or one 10 mg tablet once daily.

Treatment of Glucocorticoid-Induced Osteoporosis: The recommended dosage is one 5 mg tablet once daily, except for postmenopausal women not receiving estrogen, for whom the recommended dosage is one 10 mg tablet once daily.

Treatment of Paget's Disease of Bone: The recommended treatment regimen is 40 mg once a day for six months.

The incidence of upper gastrointestinal side effects are increased with the concomitant use of non-steroidal anti-inflammatory agents and aspirin. Absorption of Alendronate is reduced in the presence of antacids and calcium supplements.

Alendronic acid is contraindicated in patients with the following conditions: 

• Abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia.
• Inability to stand or sit upright for at least 30 minutes.
• Do not administer Alendronic acid oral solution to patients at increased risk of aspiration.
• Hypocalcemia.
• Hypersensitivity to any component of this product. Hypersensitivity reactions including urticaria and angioedema have been reported.

The commonest symptomatic side effects are constipation, diarrhoea, oesophageal ulcer, flatulence, dysphagia, musculoskeletal pain, headache, rarely rash, erythema, transient decrease in serum calcium and phosphate, nausea, vomiting, peptic ulceration, hypersensitivity reactions including urticaria and angio-oedema.

Alendronic acid should not be given to pregnant women or nursing mother.

• Upper Gastrointestinal Adverse Reactions can occur. Instruct patients to follow dosing instructions. Discontinue if new or worsening symptoms occur.
• Hypocalcemia can worsen and must be corrected prior to use.
• Severe Bone, Joint, Muscle Pain may occur. Discontinue use if severe symptoms develop.
• Osteonecrosis of the Jaw has been reported.
• Atypical Femur Fractures have been reported. Patients with new thigh or groin pain should be evaluated to rule out an incomplete femoral fracture.

Pediatric Use: Alendronic acid is not indicated for use in pediatric patients.

Renal Impairment: Alendronic acid is not recommended for patients with creatinine clearance less than 35 mL/min. No dosage adjustment is necessary in patients with creatinine clearance values between 35-60 mL/min.

Hepatic Impairment: As there is evidence that alendronate is not metabolized or excreted in the bile, no studies were conducted in patients with hepatic impairment. No dosage adjustment is necessary.

Bisphosphonate preparations

Store in a well-closed container at room temperature, 15-30°C