Alendronic Acid/ Cholecalciferol

Registered South African indications:

• Postmenopausal osteoporosis
  - To reduce the risk of fractures, including those of the hip and spine (vertebral compression fractures) and to help ensure vitamin D adequacy

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Abnormalities of the oesophagus which delay oesophageal emptying such as stricture or achalasia
• Inability to stand or sit upright for at least 30 minutes
• Hypoglycaemia
• Severe renal insufficiency (CrCl < 35ml/min)
• Pregnancy
• Breastfeeding
• Children below the age of 18 years

• Mild to moderate renal impairment
• Hepatic impairment
• Dysphagia
• Gastritis
• Duodenitis
• Recent peptic ulcer
• Active gastrointestinal bleeding
• Upper gastrointestinal surgery
• Barrett's oesophagus
• Risk factors for osteonecrosis of the jaw
• Risk factors for osteonecrosis of the auditory canal 
• Other risk factors for osteoporosis 
• History of dental disease
• Poor oral hygiene
• Periodontal disease
• Invasive procedures
• Poorly fitting dentures
• Hypoparathyroidism
• Leukaemia
• Lymphoma
• Sarcoidosis
• Fructose intolerance
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption
• Sucrase-isomaltase insufficiency

Forms avail. in SA and covered in this monograph: tab

South African registered indications and dosages

Postmenopausal osteoporosis
- To reduce the risk of fractures, including those of the hip and spine (vertebral compression fractures) and to help ensure vitamin D adequacy

Patients receiving separate Vitamin D supplement (400 IU) daily

Alendronic acid/ Cholecalciferol
70mg/70µg

• Oral (tab): 1 tab, weekly

Patients not receiving separate Vitamin D supplement

Alendronic acid/ Cholecalciferol
70mg/140µg

• Oral (tab): 1 tab, weekly

Patients should receive supplemental calcium and/or vitamin D if intake is inadequate. Consider the vitamin D intake of the individual patient from vitamins and dietary supplements. Alendronic acid/cholecalciferol provides a week’s supply of vitamin D, based on a daily dose of 400 IU and 800 IU respectively, in a single once-a-week dose

Method of administration

To be taken at least 30min before food with a full glass of plain water, beverage or medication of the day to facilitate delivery to the stomach and to reduce the potential for oesophageal irritation
Should be swallowed whole. Do not crush or chew the tablet or allow the tablet to dissolve in the mouth because of a potential for oropharyngeal ulceration
Other beverages (including mineral water), food and some medicines are likely to reduce the absorption of alendronate
Do not lie down for at least 30 minutes and not until after they have eaten. Should not be taken at bedtime or before arising for the day. Failure to follow these instructions may increase the risk of oesophageal adverse experiences

Not established for use in children below 18 years (See contraindications)

Pregnancy

South African recommendations

• Contraindicated
• Alendronic acid/cholecalciferol has not been studied in pregnant women and is therefore contraindicated
• Studies in animals have shown reproductive toxicity

Breastfeeding

South African recommendations

• Contraindicated
• Alendronic acid/cholecalciferol is contraindicated in breastfeeding women as safety and efficacy have not been established

Fertility

South African recommendations

• There is no data on foetal risk in humans. However, there is a theoretical risk of foetal harm, predominantly skeletal, if a woman becomes pregnant after completing a course of bisphosphonate therapy
• The impact of variables such as time between cessation of bisphosphonate therapy to conception, the particular bisphosphonate used, and the route of administration (intravenous versus oral) on the risk has not been studied

South African recommendations

• Mild to moderate (CrCl 35 to 60ml/min): Caution; no dose adjustment recommended
• Severe (CrCl < 35ml/min): Contraindicated

• Caution; no dose adjustment recommended

• No dose adjustment recommended

Central Nervous System Disorders

• Headache 
• Dizziness
• Vertigo
• Dysgeusia
• Asthenia

Gastrointestinal Disorders

• Abdominal pain 
• Dyspepsia
• Constipation
• Diarrhoea 
• Flatulence
• Oesophageal ulcer
• Dysphagia 
• Abdominal distension 
• Acid regurgitation
• Nausea and vomiting 
• Gastritis
• Oesophagitis
• Oesophageal erosions 
• Melena
• Oesophageal stricture
• Oropharyngeal ulceration
• Upper gastrointestinal perforations, ulcers, or bleeding

Endocrine and Metabolic Disorders

• Symptomatic hypocalcaemia

Musculoskeletal Disorders

• Musculoskeletal pain 
• Joint swelling
• osteonecrosis of the jaw
• Atypical subtrochanteric and diaphyseal femoral fractures

Skin and Subcutaneous Tissue Disorders

• Alopecia 
• Pruritus
• Rash
• Erythema
• Rash with photosensitivity
• Severe skin reactions

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity

Sensory Disorders

• Osteonecrosis of the external auditory canal
• Eye inflammation

• Food
• Beverages
• Calcium supplements
• Antacids
• Non-steroidal anti-inflammatory drugs
• Mineral oils
• Orlistat
• Cholestyramine
• Colestipol
• Anticonvulsants
• Cimetidine
• Thiazide diuretics
• Glucocorticoids

None routine. Specific cases may require

• Serum calcium
• Urinary calcium

Alendronic acid
Alendronic acid is a bisphosphonate that inhibits osteoclastic bone resorption with no direct effect on bone formation. Preferential localisation of alendronic acid to sites of active resorption has been shown in preclinical studies.  The activity of osteoclasts is inhibited, but recruitment or attachment of osteoclasts is not affected. The bone formed during treatment with alendronic acid is of normal quality.

Colecalciferol
Colecalciferol is produced within the skin under the influence of UV radiation including sunlight. In its biologically active form, colecalciferol stimulates intestinal calcium absorption, incorporation of calcium into the osteoid, and release of calcium from bone tissue. In the small intestine, it promotes rapid and delayed calcium uptake. In the kidney, it inhibits the excretion of calcium and phosphate by promoting tubular resorption. The production of parathyroid hormone (PTH) in the parathyroids is inhibited directly by the biologically active form of colecalciferol. PTH secretion is inhibited additionally by the increased calcium uptake in the small intestine under the influence of biologically active cholecalciferol.

COMBINATION PREPARATIONS

Alendronic acid/ Cholecalciferol

Tablet 70mg/140μg (equiv. to Vit D 5600 I.U)

• Fosavance 5600 (MSD) originator