Alendronic Acid + Vitamin D3

Approved Indications:

• Treatment of Osteoporosis in Postmenopausal Women: Reduces the risk of vertebral and hip fractures.
• Treatment of Osteoporosis in Men: Increases bone mass to reduce the incidence of fractures.
• Treatment of Glucocorticoid-Induced Osteoporosis: In both men and women receiving systemic glucocorticoids.
• Prevention of Osteoporosis in High-Risk Groups: Including postmenopausal women with low bone mass and individuals with chronic corticosteroid use.
• Treatment of Vitamin D Deficiency Concurrent with Osteoporosis: Corrects vitamin D insufficiency to ensure optimal calcium absorption and bone health.

Important Off-Label/Clinically Accepted Uses:

• Paget’s Disease of Bone (when coexisting vitamin D deficiency exists): For patients with metabolic bone remodeling abnormalities and insufficient vitamin D levels.

Adults (including elderly):

• Alendronic Acid 70 mg + Vitamin D3 2800 IU or 5600 IU: One tablet once weekly.
• Administer orally, with plain water (≥240 mL), at least 30 minutes before the first food, beverage, or medication of the day.
• Patient must remain upright (sitting or standing) for at least 30 minutes post-dose to reduce esophageal irritation risk.

Pediatrics:

• Not recommended for use in children and adolescents due to lack of safety and efficacy data.

Renal Impairment:

• Contraindicated in patients with creatinine clearance <35 mL/min.
• No dosage adjustment needed for mild to moderate renal impairment (CrCl ≥35 mL/min).

Hepatic Impairment:

• No dose adjustment necessary; hepatic metabolism is minimal.

Duration:

• Long-term use should be periodically re-evaluated; typically reassessed after 3–5 years of continuous therapy.

Alendronic acid is a nitrogen-containing bisphosphonate that binds to hydroxyapatite crystals in bone, specifically at sites of active resorption. It inhibits farnesyl pyrophosphate synthase, a key enzyme in the mevalonate pathway, thus preventing prenylation of small GTPase signaling proteins in osteoclasts. This results in impaired osteoclast activity, reduced bone resorption, and increased bone mineral density. Vitamin D3 (cholecalciferol) is a fat-soluble vitamin that is metabolized to calcitriol, the active form that binds to vitamin D receptors, promoting calcium and phosphate absorption from the gut, maintaining calcium balance, and enhancing bone mineralization. Together, they synergistically improve bone strength and reduce fracture risk.

• Absorption (Alendronic Acid): Poorly absorbed (~0.6–0.7%) from the GI tract; food and beverages (except water) significantly reduce absorption.
• Absorption (Vitamin D3): Well absorbed in the small intestine, dependent on fat digestion and bile salts.
• Distribution: Alendronate is ~78% bound to plasma proteins; Vitamin D3 is widely distributed in adipose and muscle tissue.
• Metabolism: Alendronic acid is not metabolized. Vitamin D3 undergoes hepatic conversion to 25-hydroxyvitamin D and renal conversion to active 1,25-dihydroxyvitamin D.
• Half-life:
• Alendronic Acid: Up to 10 years (due to bone incorporation)
• Vitamin D3: ~15–25 days for 25(OH)D3
• Elimination:
• Alendronic acid: Renal excretion of unchanged drug
• Vitamin D3: Biliary and renal excretion of metabolites

• Pregnancy: Alendronic Acid is classified as Pregnancy Category C. Not recommended during pregnancy due to lack of controlled human studies and potential risk of fetal skeletal anomalies.
• Lactation: It is not known whether alendronate is excreted in human milk. Vitamin D3 is excreted into breast milk, but the amount is generally considered safe at standard doses. Caution advised, particularly with high doses or prolonged use. Monitor infant calcium levels if maternal supplementation is high.

• Primary Class: Bisphosphonate + Vitamin D supplement
• Subclass: Anti-resorptive agent + Fat-soluble vitamin combination
• Formulation Type: Combination therapy for bone health maintenance and fracture prevention

• Hypersensitivity to alendronic acid, cholecalciferol, or any component of the formulation
• Abnormalities of the esophagus (e.g., stricture, achalasia) that delay esophageal emptying
• Inability to stand or sit upright for at least 30 minutes
• Hypocalcemia (must be corrected before initiation)
• Severe renal impairment (creatinine clearance <35 mL/min)
• Hypercalcemia or hypervitaminosis D

• Esophageal Adverse Reactions: Risk of esophagitis, ulcers, and erosions; instruct patient on proper administration.
• Hypocalcemia: Must be corrected before therapy. Monitor calcium and vitamin D levels.
• Osteonecrosis of the Jaw (ONJ): Rare but serious, especially in cancer patients or after dental procedures.
• Atypical Femoral Fractures: Discontinue if prodromal thigh/groin pain occurs.
• Renal Impairment: Use cautiously in patients with mild-to-moderate renal dysfunction.
• Vitamin D Toxicity Risk: With prolonged high dosing or renal impairment.
• Monitoring: Periodic assessment of bone mineral density, calcium, phosphorus, renal function, and 25(OH)D levels.

Common (≥1%):

• Gastrointestinal: Abdominal pain, dyspepsia, constipation, diarrhea, nausea
• Musculoskeletal: Bone, joint, or muscle pain
• Nervous System: Headache, dizziness

Less Common:

• Esophagitis, esophageal ulceration or perforation
• Hypocalcemia, muscle cramps
• Rash, photosensitivity

Serious & Rare:

• Osteonecrosis of the jaw
• Severe musculoskeletal pain
• Atypical femoral fractures
• Anaphylaxis or angioedema (rare hypersensitivity)

• Calcium or other mineral supplements, antacids, and iron: Decrease absorption of alendronic acid; separate administration by at least 30 minutes.
• Thiazide diuretics: May increase risk of hypercalcemia when combined with vitamin D.
• Magnesium-containing antacids: May increase risk of hypermagnesemia.
• NSAIDs: Increased risk of GI irritation when used concomitantly.
• Systemic corticosteroids: May exacerbate osteoporosis; vitamin D is useful but monitor calcium.

Enzyme Systems:

• Vitamin D metabolism involves CYP27B1 and CYP24A1 but no significant CYP450 induction/inhibition by alendronic acid.

• Recent guidelines emphasize combined vitamin D and bisphosphonate therapy as superior in osteoporosis management versus bisphosphonate monotherapy, especially in individuals with vitamin D insufficiency.
• EMA and FDA have highlighted ongoing risk of atypical femoral fractures and recommend therapy review after 3–5 years.
• Updated dental management protocols suggest dental screening before initiation to prevent ONJ.

• Temperature: Store below 30°C.
• Humidity/Light: Protect from moisture and direct light.
• Handling Precautions: Do not split or chew tablets. Store in original blister to prevent exposure to humidity.
• Reconstitution: Not applicable. Tablets are to be used as-is.