Alendronic acid + Colecalciferol

Oral
Osteoporosis in men, Osteoporosis in postmenopausal women

CrCl (mL/min)	Dosage
<35	Not recommended.

Alendronic acid + Colecalciferol Should be taken on an empty stomach. Take in upright position w/ water at least 30 min before food & remain in upright position for at least 30 min to reduce oesophageal irritation.

Hypocalcaemia; abnormalities of the oesophagus that delay oesophageal emptying (e.g. stricture or achalasia); inability to stand or sit upright for at least 30 minutes.

Patient with active upper gastrointestinal problems (e.g. dysphagia, known Barrett's oesophagus or other oesophageal diseases, duodenitis, gastritis, ulcers); recent history (within the previous year) of major gastrointestinal disease (e.g. active gastrointestinal bleeding, peptic ulcer, surgery of the upper gastrointestinal tract other than pyloroplasty); risk factors for osteonecrosis of the jaw (e.g. cancer, anaemia, coagulopathy; history of dental disease, poor oral hygiene, periodontal disease, poorly fitting dentures, invasive dental procedures [e.g. tooth extraction, dental implants]; smoking; concomitant treatment with chemotherapy, corticosteroids, angiogenesis inhibitors or radiotherapy); risk factors for osteonecrosis of external auditory canal (e.g. infection, trauma); other disorders affecting mineral metabolism (e.g. hypoparathyroidism, vitamin D deficiency); condition associated with unregulated overproduction of calcitriol (e.g. leukaemia, lymphoma, sarcoidosis); gastrointestinal malabsorption syndrome. Ensure adequate Ca and vitamin D intake during treatment; dietary supplementation is recommended if dietary intake is inadequate. Renal impairment (CrCl <35 mL/min). Pregnancy and lactation; alendronic acid + colecalciferol is indicated for postmenopausal women, therefore it is not intended for use in women of reproductive potential.

Significant: Atypical subtrochanteric and diaphyseal femoral fractures (particularly during prolonged use); severe (occasionally debilitating) bone, joint and/or muscle pain; oesophagitis, oesophageal ulcers, oesophageal erosions, dysphagia; osteonecrosis of the jaw and external auditory canal; hypophosphataemia or hyperphosphataemia; ocular effects (e.g. uveitis, episcleritis, scleritis). Rarely, symptomatic hypocalcaemia, oesophageal stricture, gastric and duodenal ulcers.
Ear and labyrinth disorders: Vertigo.
Gastrointestinal disorders: Abdominal pain, abdominal distension, acid regurgitation, dyspepsia, constipation, diarrhoea, flatulence, dysgeusia.
General disorders and administration site conditions: Asthenia, peripheral oedema.
Musculoskeletal and connective tissue disorders: Joint swelling.
Nervous system disorders: Headache, dizziness.
Skin and subcutaneous tissue disorders: Alopecia, pruritus.

PO: C

Maintain good oral hygiene.

Correct hypocalcaemia and vitamin D deficiency before starting treatment. Evaluate serial BMD at baseline and every 1-3 years during treatment, then every 2-4 years during a drug holiday. Monitor height and weight (annually); serum Ca and 25-hydroxyvitamin D. Consider monitoring of biochemical markers of bone turnover (e.g. fasting serum C-terminal telopeptide [CTX] or urinary N-terminal telopeptide [NTX]) at baseline, 3 months, and 6 months. Assess for signs and symptoms of chronic back pain and oesophageal reaction (e.g. dysphagia, retrosternal pain, new or worsening heartburn).

Symptoms: Alendronic acid: Hypocalcaemia, hypophosphataemia, upper gastrointestinal effects (e.g. heartburn, upset stomach, gastritis, ulcer, oesophagitis). Management: Do not induce vomiting to prevent oesophageal irritation; patient must remain in a fully upright position. Milk or antacids may be given to bind alendronic acid.

Alendronic acid: Antacids, Ca supplements or other oral medications containing polyvalent cations may interfere with the absorption of alendronic acid. Increased risk of gastrointestinal adverse events with aspirin or NSAIDs.
Colecalciferol: Mineral oil, orlistat, and bile acid sequestrants (e.g. colestyramine, colestipol) may impair vitamin D absorption. Anticonvulsants, cimetidine and thiazides may increase vitamin D catabolism.

Alendronic acid: May reduce absorption with food and beverages (particularly coffee, orange juice, and mineral water).

Alendronic acid: May interfere with diagnostic imaging agents (e.g. technetium-99m-diphosphonate) in bone scans.

Description:
Mechanism of Action: Alendronic acid, an aminobisphosphonate, inhibits bone resorption through actions on osteoclasts or osteoclast precursors. It decreases the rate of bone resorption, resulting in indirect increase in bone mineral density (BMD).
Colecalciferol is a provitamin. Its active metabolite, 1,25-dihydroxyvitamin D₃ (calcitriol), stimulates Ca and phosphate absorption from the small intestine and regulates serum Ca levels, renal excretion of Ca and phosphate, and bone formation and resorption.
Synonym(s): Colecalciferol: Cholecalciferol; vitamin D₃.
Pharmacokinetics:
Absorption: Alendronic acid: Bioavailability: 0.6% (fasting). Food and beverages may reduce absorption.
Colecalciferol: Absorbed in the small intestine.
Distribution: Alendronic acid: Plasma protein binding: 78%.
Colecalciferol: Enters the blood as part of chylomicrons; rapidly distributed mostly to the liver. Enters breast milk. Binds to vitamin D-binding protein.
Metabolism: Alendronic acid: Not metabolised.
Colecalciferol: Metabolised in the liver via hydroxylation into 25-hydroxyvitamin D₃ (calcifediol), then metabolised in the kidney to the active metabolite 1,25-dihydroxyvitamin D₃ (calcitriol); further hydroxylation occurs before elimination and a small percentage of colecalciferol undergoes glucuronidation before elimination.
Excretion: Alendronic acid: Via urine; faeces (as unabsorbed drug). Elimination half-life: >10 years.
Colecalciferol: Via faeces.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 2088, Alendronic Acid. https://pubchem.ncbi.nlm.nih.gov/compound/Alendronic-Acid. Accessed Oct. 30, 2024.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 5280795, Cholecalciferol. https://pubchem.ncbi.nlm.nih.gov/compound/Cholecalciferol. Accessed Oct. 30, 2024.

Store between 15-30°C. Protect from light and moisture.

Agents Affecting Bone Metabolism

M05BB03 - alendronic acid and colecalciferol ; Belongs to the class bisphosphonates, combinations. Used in the treatment of bone diseases.

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