Usage
- Medical Conditions: Alendronic acid + vitamin D3 is prescribed for the treatment and prevention of osteoporosis in postmenopausal women and in men. It helps increase bone mass and reduce the risk of fractures, including hip and spine fractures. It’s also used for glucocorticoid-induced osteoporosis.
- Pharmacological Classification: Bisphosphonate, Vitamin Supplement
- Mechanism of Action: Alendronic acid inhibits osteoclast activity, the cells responsible for bone resorption. Vitamin D3 enhances calcium absorption, essential for bone formation. This combined action leads to increased bone mineral density and reduced fracture risk.
Alternate Names
- International/Regional Variations: Alendronate sodium + cholecalciferol.
- Brand Names: Fosamax Plus D, Fosavance.
How It Works
- Pharmacodynamics: Alendronate binds to hydroxyapatite crystals in bone, inhibiting osteoclast activity and bone resorption. Vitamin D3 promotes calcium absorption in the gut and maintains serum calcium levels, crucial for bone mineralization.
- Pharmacokinetics:
- Alendronate: Poorly absorbed orally (less than 10%). Absorption is further reduced by food, beverages, and some medications. Distributes rapidly to bone or is excreted in urine. Not metabolized. Eliminated primarily through renal excretion.
- Vitamin D3: Absorbed in the small intestine. Converted to active metabolites in the liver and kidneys. Stored in adipose tissue.
- Mode of Action: Alendronate inhibits osteoclast activity by disrupting the mevalonate pathway within these cells, leading to apoptosis (programmed cell death). Vitamin D3 binds to vitamin D receptors, affecting gene transcription and influencing calcium homeostasis.
- Receptor Binding, Enzyme Inhibition: Alendronate targets farnesyl pyrophosphate synthase in the mevalonate pathway of osteoclasts. Vitamin D3 acts through vitamin D receptors.
- Elimination Pathways: Alendronate is primarily excreted unchanged in the urine. Vitamin D3 metabolites are excreted in bile and feces.
Dosage
Standard Dosage
Adults:
- One 70 mg alendronate + 2800 IU (or 5600 IU) vitamin D3 tablet orally once weekly. The 5600 IU dose is generally more appropriate for postmenopausal women and men with osteoporosis at risk for vitamin D insufficiency.
- Administer at least 30 minutes before the first food, beverage, or other medication of the day, with a full glass of plain water only.
Children: Use is not recommended. Safety and efficacy in pediatric patients have not been established.
Special Cases:
- Elderly Patients: No dosage adjustment is necessary.
- Patients with Renal Impairment: Not recommended for creatinine clearance less than 35 mL/min. No dosage adjustment is necessary for creatinine clearance greater than 35 mL/min.
- Patients with Hepatic Dysfunction: No specific dosage adjustment is provided in the available resources.
- Patients with Comorbid Conditions: Caution should be exercised in patients with active upper gastrointestinal problems. Correct hypocalcemia before initiating therapy. Monitor serum calcium and phosphate levels in patients taking glucocorticoids.
Clinical Use Cases
Alendronic acid + vitamin D3 is not typically indicated for acute medical settings such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. It is primarily used for long-term management of osteoporosis.
Dosage Adjustments
Adjustments should be based on creatinine clearance. Consider additional vitamin D supplementation in patients at risk for vitamin D insufficiency.
Side Effects
Common Side Effects
- Gastrointestinal: Abdominal pain, dyspepsia, acid reflux, constipation, diarrhea, nausea.
- Musculoskeletal: Bone, muscle, or joint pain.
- Neurological: Headache, dizziness.
Rare but Serious Side Effects
- Esophageal irritation or ulceration.
- Osteonecrosis of the jaw (rare, typically associated with dental procedures).
- Atypical femoral fractures.
- Severe hypocalcemia.
Long-Term Effects
- Increased risk of atypical femoral fractures with prolonged use.
- Potential for esophageal strictures with chronic irritation.
Adverse Drug Reactions (ADR)
- Severe allergic reactions (anaphylaxis).
- Esophageal perforation.
Contraindications
- Hypersensitivity to alendronate or vitamin D3.
- Esophageal abnormalities (achalasia, stricture).
- Inability to sit or stand upright for at least 30 minutes.
- Hypocalcemia.
- Severe renal insufficiency (creatinine clearance < 35 mL/min).
Drug Interactions
- Calcium supplements, antacids, and other medications containing polyvalent cations can reduce alendronate absorption.
- NSAIDs may increase the risk of gastrointestinal adverse events.
- Medications such as cholestyramine, orlistat, mineral oil, and some corticosteroids can reduce vitamin D absorption.
- Certain medications (e.g., anticonvulsants, cimetidine, thiazides) can increase vitamin D catabolism.
- Food and beverages can decrease alendronate absorption.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Not established. Alendronate should not be used during pregnancy.
- Fetal Risks: Potential for dystocia related to hypocalcemia in animal studies.
- Breastfeeding: Alendronate excretion in breast milk is unknown. Cholecalciferol passes into breast milk. Alendronate should not be used during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Inhibits osteoclast-mediated bone resorption (alendronate) and enhances calcium absorption (vitamin D3).
- Side Effects: GI disturbances, musculoskeletal pain, esophageal irritation, osteonecrosis of the jaw (rare).
- Contraindications: Esophageal abnormalities, inability to sit upright, hypocalcemia, severe renal impairment.
- Drug Interactions: Calcium supplements, antacids, NSAIDs, medications affecting vitamin D absorption.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: 70 mg alendronate + 2800/5600 IU vitamin D3 once weekly.
- Monitoring Parameters: Serum calcium, phosphate, 25-hydroxyvitamin D, bone mineral density.
Popular Combinations
Calcium and vitamin D supplementation may be necessary for patients with inadequate dietary intake.
Precautions
- Ensure adequate calcium and vitamin D intake.
- Correct hypocalcemia before starting therapy.
- Advise patients about proper administration to minimize esophageal irritation.
- Monitor for signs of esophageal adverse events and osteonecrosis of the jaw.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Alendronic Acid + Vitamin D3?
A: One 70 mg alendronate + 2800 IU (or 5600 IU) vitamin D3 tablet once weekly. The 5600 IU dose is generally more appropriate for most patients with osteoporosis.
Q2: How should Alendronic Acid + Vitamin D3 be taken?
A: Take with a full glass of plain water only, at least 30 minutes before the first food, beverage, or other medication of the day. Remain upright for at least 30 minutes after taking the dose.
Q3: What are the common side effects of Alendronic Acid + Vitamin D3?
A: Common side effects include gastrointestinal issues (abdominal pain, heartburn, constipation, diarrhea), bone or joint pain, headache, and dizziness.
Q4: What are the serious side effects of Alendronic Acid + Vitamin D3?
A: Rare but serious side effects include esophageal irritation, osteonecrosis of the jaw, atypical femoral fractures, and severe hypocalcemia.
Q5: Who should not take Alendronic Acid + Vitamin D3?
A: Contraindicated in patients with hypersensitivity, esophageal abnormalities, inability to sit upright, hypocalcemia, and severe renal impairment.
Q6: What are the drug interactions of Alendronic Acid + Vitamin D3?
A: Interacts with calcium supplements, antacids, NSAIDs, and medications affecting vitamin D absorption. Avoid food and beverages (other than plain water) for at least 30 minutes after administration.
Q7: Can Alendronic Acid + Vitamin D3 be taken during pregnancy or breastfeeding?
A: No, it is contraindicated during pregnancy and breastfeeding.
Q8: What should patients be monitored for while taking Alendronic Acid + Vitamin D3?
A: Serum calcium, phosphate, 25-hydroxyvitamin D levels, and bone mineral density should be monitored, along with any signs of esophageal or jaw problems.
Q9: What if a patient misses a dose of Alendronic Acid + Vitamin D3?
A: Take the missed dose the next morning after remembering. Do not take two doses on the same day. Return to the regular once-weekly schedule on the originally chosen day.
Q10: How long should a patient take Alendronic Acid + Vitamin D3?
A: The optimal duration of treatment should be evaluated on a patient-specific basis, considering the benefits and potential risks, especially after 5 years of use.
