Drugs List

Therapeutic Indications

Uses

Treatment of osteoporosis in postmenopausal women to prevent fractures

Treatment of postmenopausal osteoporosis in patients at risk of vitamin D insufficiency. Treatment reduces risk of vertebral and hip fractures.

Contraindications

Children under 18 years
Inability to stand or sit upright for at least 30 minutes
Achalasia
Breastfeeding
Delayed oesophageal emptying
Galactosaemia
Hereditary fructose intolerance
Hypocalcaemia
Oesophageal obstruction
Oesophageal strictures
Pregnancy
Renal impairment - creatinine clearance below 35ml/minute

Precautions and Warnings

Duodenitis
Dysphagia
Gastritis
Gastrointestinal haemorrhage
Glucose-galactose malabsorption syndrome
History of gastrointestinal ulceration
Hypoparathyroidism
Lactose intolerance
Leukaemia
Lymphoma
Malabsorption syndrome
Oesophagitis
Peptic ulcer
Sarcoidosis
Upper gastrointestinal surgery

Calcium supplements may be required if risk of calcium/vitamin D deficiency
Consider a dental exam & appropriate preventive dentistry before treatment
Consider other causes of osteoporosis
Contains lactose
Preparation contains sucrose
Patient must remain upright for at least 30 minutes after dose
Correct disturbances of calcium and mineral metabolism before initiation
Evaluate benefit/risk in long term use ( > 5 years)
Monitor serum calcium levels
Monitor serum/urinary calcium in sarcoidosis, leukaemia & lymphoma patients
Advise patient to report any ear pain, discharge or infection
Advise patient to report any new thigh, hip or groin pain
Patients should seek medical attention upon signs of oesophageal irritation
Consider discontinuation if atypical femur fracture is suspected
Discontinue if symptoms of oesophageal irritation occur
Advise patients to avoid aspirin and NSAID use
Adequate daily intake of calcium essential
Advise patient not to take two doses on the same day if a dose is missed
Advise patient of need for high oral hygiene standards
Advise patient to follow dosage instructions closely
Advise patient to report any dental mobility, pain or swelling
Patient to inform dentist of bisphosphonate use: avoid invasive procedures

Osteonecrosis of the jaw (ONJ) has been reported in patients treated with bisphosphonates, most cases have been in patients with advanced malignancies involving bone. In studies patients who developed ONJ had known risk factors, including a diagnosis of cancer with bone lesions, concomitant therapies (e.g., chemotherapy, antiangiogenic biologics, corticosteroids, radiotherapy to head and neck), poor oral hygiene, invasive dental procedures including extractions and dental implants, co-morbid disorders (e.g., pre-existing dental disease, anaemia, coagulopathy, infection) and previous treatment with bisphosphonates.

Osteonecrosis of the external auditory canal has been reported very rarely with bisphosphonates, mainly in association with long term therapy (2 years or longer). Risk factors include steroid use and chemotherapy and/or local risk factors as infection or trauma. The possibility of osteonecrosis of the external auditory canal should be considered in patients receiving bisphosphonates who present with ear symptoms including chronic ear infections.

Atypical femoral fractures have been reported in patients receiving bisphosphonates. Atypical femoral fractures may occur with little or no trauma in the subtrochanteric and diaphyseal regions of the femur. Patients presenting with symptoms of atypical femoral fracture should be evaluated for an incomplete femoral fracture and discontinuation must be considered.

Alendronic acid can cause irritation of the upper gastrointestinal mucosa. In patients with Barrett's oesophagus, the benefits and potential risks should be considered on an individual patient basis.

Pregnancy and Lactation

Pregnancy

Alendronic acid with colecalciferol is contraindicated in pregnancy.

The manufacturer does not recommend the use of alendronic acid with colecalciferol during pregnancy.

However, due to the low oral bioavailability and rapid plasma clearance, the amount potentially crossing the placenta may not be clinically significant in normal dosing (Briggs, 2015).

Alendronic acid is slowly released from bone, therefore its use before pregnancy may result in low-level continuous exposure throughout gestation (Briggs, 2015).

Schaefer (2015) advises that accidental dosing of alendronic acid during pregnancy, or pregnancy arising during treatment, is not cause for interruption of the pregnancy or additional diagnostic procedures.

Some experts recommend monitoring the infant's serum calcium during the first 2 months postpartum if the mother receives a bisphosphonate during pregnancy (Lactmed, 2018).

Animal studies have shown reproductive toxicity and dystocia related hypocalcaemia, high doses of vitamin D have also been shown to be teratogenic in animal experiments. High doses of vitamin D may potentially cause hypercalcaemia in the mother and foetus.

Lactation

Alendronic acid with colecalciferol is contraindicated in breastfeeding.

Manufacturer does not recommend using alendronic acid with colecalciferol during breastfeeding.

The molecular weight of alendronic acid is low enough to allow secretion in milk. However, the low plasma concentrations and rapid plasma clearance expected with alendronic acid suggests that amounts of alendronic acid in milk are likely to be minimal (Briggs, 2015). If alendronic acid is required during breastfeeding, Schaefer (2015) advises that the mother avoids nursing for a minimum of 2 hours after dosing.

Some experts recommend monitoring the infant's serum calcium during the first 2 months postpartum if the mother receives a bisphosphonate during pregnancy or nursing (Lactmed, 2018).

Limited data indicate that breastfeeding after cessation of long-term bisphosphonate treatment appears to have no adverse effects on the infant.

Vitamin D is considered low risk during breastfeeding. Vitamin D is secreted in breast milk in limited amounts. The amount of vitamin D in milk has a direct relationship with the amount of vitamin D present in maternal serum. Excessive maternal intake of vitamin D may produce elevated calcium levels in the infant.

Side Effects

Abdominal distension
Abdominal pain
Acid regurgitation
Alopecia
Angioedema
Asthenia
Atypical femoral fracture
Constipation
Decrease in plasma calcium
Decrease in serum phosphate
Diarrhoea
Dizziness
Dysgeusia
Dyspepsia
Dysphagia
Episcleritis
Erythema
Fever
Flatulence
Gastritis
Gastro-intestinal perforation
Gastro-intestinal ulceration
Gastrointestinal bleeding
Headache
Hypersensitivity reactions
Hypocalcaemia
Joint swelling
Malaise
Melaena
Musculoskeletal pain
Myalgia
Nausea
Oesophageal erosions
Oesophageal stricture
Oesophageal ulceration
Oesophagitis
Oropharyngeal ulceration
Osteonecrosis (primarily of the jaw)
Osteonecrosis of the external auditory canal
Peripheral oedema
Photosensitivity
Pruritus
Rash
Scleritis
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Urticaria
Uveitis
Vertigo
Vomiting

Presentation

Tablets containing alendronic acid with colecalciferol.

Drugs List

Therapeutic Indications

Uses

Treatment of osteoporosis in postmenopausal women to prevent fractures

Treatment of postmenopausal osteoporosis in patients at risk of vitamin D insufficiency. Treatment reduces risk of vertebral and hip fractures.

Dosage

Adults

Contraindications

Children under 18 years
Inability to stand or sit upright for at least 30 minutes
Achalasia
Breastfeeding
Delayed oesophageal emptying
Galactosaemia
Hereditary fructose intolerance
Hypocalcaemia
Oesophageal obstruction
Oesophageal strictures
Pregnancy
Renal impairment - creatinine clearance below 35ml/minute

Precautions and Warnings

Duodenitis
Dysphagia
Gastritis
Gastrointestinal haemorrhage
Glucose-galactose malabsorption syndrome
History of gastrointestinal ulceration
Hypoparathyroidism
Lactose intolerance
Leukaemia
Lymphoma
Malabsorption syndrome
Oesophagitis
Peptic ulcer
Sarcoidosis
Upper gastrointestinal surgery

Calcium supplements may be required if risk of calcium/vitamin D deficiency
Consider a dental exam & appropriate preventive dentistry before treatment
Consider other causes of osteoporosis
Contains lactose
Preparation contains sucrose
Patient must remain upright for at least 30 minutes after dose
Correct disturbances of calcium and mineral metabolism before initiation
Evaluate benefit/risk in long term use ( > 5 years)
Monitor serum calcium levels
Monitor serum/urinary calcium in sarcoidosis, leukaemia & lymphoma patients
Advise patient to report any ear pain, discharge or infection
Advise patient to report any new thigh, hip or groin pain
Patients should seek medical attention upon signs of oesophageal irritation
Consider discontinuation if atypical femur fracture is suspected
Discontinue if symptoms of oesophageal irritation occur
Advise patients to avoid aspirin and NSAID use
Adequate daily intake of calcium essential
Advise patient not to take two doses on the same day if a dose is missed
Advise patient of need for high oral hygiene standards
Advise patient to follow dosage instructions closely
Advise patient to report any dental mobility, pain or swelling
Patient to inform dentist of bisphosphonate use: avoid invasive procedures

Osteonecrosis of the jaw (ONJ) has been reported in patients treated with bisphosphonates, most cases have been in patients with advanced malignancies involving bone. In studies patients who developed ONJ had known risk factors, including a diagnosis of cancer with bone lesions, concomitant therapies (e.g., chemotherapy, antiangiogenic biologics, corticosteroids, radiotherapy to head and neck), poor oral hygiene, invasive dental procedures including extractions and dental implants, co-morbid disorders (e.g., pre-existing dental disease, anaemia, coagulopathy, infection) and previous treatment with bisphosphonates.

Osteonecrosis of the external auditory canal has been reported very rarely with bisphosphonates, mainly in association with long term therapy (2 years or longer). Risk factors include steroid use and chemotherapy and/or local risk factors as infection or trauma. The possibility of osteonecrosis of the external auditory canal should be considered in patients receiving bisphosphonates who present with ear symptoms including chronic ear infections.

Atypical femoral fractures have been reported in patients receiving bisphosphonates. Atypical femoral fractures may occur with little or no trauma in the subtrochanteric and diaphyseal regions of the femur. Patients presenting with symptoms of atypical femoral fracture should be evaluated for an incomplete femoral fracture and discontinuation must be considered.

Alendronic acid can cause irritation of the upper gastrointestinal mucosa. In patients with Barrett's oesophagus, the benefits and potential risks should be considered on an individual patient basis.

Pregnancy and Lactation

Pregnancy

Alendronic acid with colecalciferol is contraindicated in pregnancy.

The manufacturer does not recommend the use of alendronic acid with colecalciferol during pregnancy.

However, due to the low oral bioavailability and rapid plasma clearance, the amount potentially crossing the placenta may not be clinically significant in normal dosing (Briggs, 2015).

Alendronic acid is slowly released from bone, therefore its use before pregnancy may result in low-level continuous exposure throughout gestation (Briggs, 2015).

Schaefer (2015) advises that accidental dosing of alendronic acid during pregnancy, or pregnancy arising during treatment, is not cause for interruption of the pregnancy or additional diagnostic procedures.

Some experts recommend monitoring the infant's serum calcium during the first 2 months postpartum if the mother receives a bisphosphonate during pregnancy (Lactmed, 2018).

Animal studies have shown reproductive toxicity and dystocia related hypocalcaemia, high doses of vitamin D have also been shown to be teratogenic in animal experiments. High doses of vitamin D may potentially cause hypercalcaemia in the mother and foetus.

Lactation

Alendronic acid with colecalciferol is contraindicated in breastfeeding.

Manufacturer does not recommend using alendronic acid with colecalciferol during breastfeeding.

The molecular weight of alendronic acid is low enough to allow secretion in milk. However, the low plasma concentrations and rapid plasma clearance expected with alendronic acid suggests that amounts of alendronic acid in milk are likely to be minimal (Briggs, 2015). If alendronic acid is required during breastfeeding, Schaefer (2015) advises that the mother avoids nursing for a minimum of 2 hours after dosing.

Some experts recommend monitoring the infant's serum calcium during the first 2 months postpartum if the mother receives a bisphosphonate during pregnancy or nursing (Lactmed, 2018).

Limited data indicate that breastfeeding after cessation of long-term bisphosphonate treatment appears to have no adverse effects on the infant.

Vitamin D is considered low risk during breastfeeding. Vitamin D is secreted in breast milk in limited amounts. The amount of vitamin D in milk has a direct relationship with the amount of vitamin D present in maternal serum. Excessive maternal intake of vitamin D may produce elevated calcium levels in the infant.

Counselling

The tablet should be swallowed whole and not sucked or chewed and washed down with a full glass of plain (not mineral) water only.

All doses should be taken 30 minutes before the first food, beverage or medication of the day.

Also advise patient that they should remain upright for at least 30 minutes after dose and until after first food of the day. They should not take the tablets at bedtime or before rising for the day.

Inform patient that failure to follow these instructions may increase their risk of oesophageal problems.

Advise patient to wait at least 30 minutes after taking alendronic acid before taking any other oral medication.

Advise patient that if they forget a dose, they should take it the morning after they remember, but they should not take two doses in a single day. Patients should return to the original schedule of one tablet once a week on their chosen day.

Advise patient to maintain adequate oral hygiene during and after treatment with bisphosphonates.

Advise patient not to self medicate with aspirin or NSAIDS.

Advise patient to discontinue treatment and seek medical attention if they develop signs of oesophageal irritation (dysphagia, new or worsening heartburn, pain on swallowing or retrosternal pain).

Advise patient to report any oral symptoms such as dental mobility, pain or swelling.

Advise patient to report any ear pain, discharge or infection.

Side Effects

Abdominal distension
Abdominal pain
Acid regurgitation
Alopecia
Angioedema
Asthenia
Atypical femoral fracture
Constipation
Decrease in plasma calcium
Decrease in serum phosphate
Diarrhoea
Dizziness
Dysgeusia
Dyspepsia
Dysphagia
Episcleritis
Erythema
Fever
Flatulence
Gastritis
Gastro-intestinal perforation
Gastro-intestinal ulceration
Gastrointestinal bleeding
Headache
Hypersensitivity reactions
Hypocalcaemia
Joint swelling
Malaise
Melaena
Musculoskeletal pain
Myalgia
Nausea
Oesophageal erosions
Oesophageal stricture
Oesophageal ulceration
Oesophagitis
Oropharyngeal ulceration
Osteonecrosis (primarily of the jaw)
Osteonecrosis of the external auditory canal
Peripheral oedema
Photosensitivity
Pruritus
Rash
Scleritis
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Urticaria
Uveitis
Vertigo
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: November 2015

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Bentexo 70mg/ 5600IU tablets. Consilient Health Ltd. Revised March 2018.
Summary of Product Characteristics: Fosavance tablets. Merck Sharp and Dohme Ltd. Revised February 2017.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 18 January 2019.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Alendronate. Last revised: 03 December 2018.