Drugs List

Therapeutic Indications

Uses

Treatment of osteoporosis in postmenopausal women to prevent fractures

Contraindications

Children under 18 years
Inability to stand or sit upright for at least 30 minutes
Achalasia
Breastfeeding
Delayed oesophageal emptying
Hypocalcaemia
Oesophageal obstruction
Oesophageal strictures
Pregnancy
Renal impairment - glomerular filtration rate below 35ml/minute

Precautions and Warnings

Duodenitis
Dysphagia
Galactosaemia
Gastritis
Gastrointestinal haemorrhage
Glucose-galactose malabsorption syndrome
History of gastrointestinal ulceration
Hypoparathyroidism
Lactose intolerance
Oesophagitis
Peptic ulcer
Upper gastrointestinal surgery
Vitamin D deficiency

Sodium content of effervescent preparation may be significant
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
Some formulations contain hydroxybenzoate
Some formulations contain lactose
Some formulations contain sunset yellow (E110); may cause allergic reaction
Patient must remain upright for at least 30 minutes after dose
Correct disturbances of calcium and mineral metabolism before initiation
Dental check-ups advisable during long-term treatment
Ensure patient's dietary intake of calcium and vitamin D is adequate
Evaluate benefit/risk in long term use ( > 5 years)
Monitor serum calcium levels
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 femoral fracture occurs
Discontinue if symptoms of oesophageal irritation occur
Advise patients to avoid aspirin and NSAID use
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.

Dental examination with appropriate preventative procedures and an individual benefit-risk assessment is recommended prior to bisphosphonate therapy in patients with risk factors for ONJ. While on treatment, patients should avoid invasive dental procedures if possible. Good oral hygiene practices and regular routine dental check-ups should be maintained during treatment with bisphosphonates.

For patients who develop ONJ during treatment, dental surgery may exacerbate the condition. If ONJ occurs during treatment with bisphosphonates, use clinical judgement and guide the management plan of each patient based on individual benefit/risk evaluation. The management plan for patients with ONJ should be set up in close collaboration between the treating physician and a dentist or oral surgeon with expertise in ONJ. Temporary interruption of treatment should be considered until the condition resolves and contributing risk factors are mitigated where possible.

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. Consider discontinuation of bisphosphonate therapy in patients suspected to have an atypical femoral fracture pending an individual risk/benefit assessment. During bisphosphonate therapy, advise patients to report new or unusual thigh, hip or groin pain. Patients presenting with such symptoms should be evaluated for an incomplete femoral fracture.

Alendronic acid is not recommended for children under 18 years of age. A study in a small number of paediatric patients with osteogenesis imperfecta were insufficient to support its use in children. However, some sources suggest that bisphosphonates have been used in the management of severe forms of osteogenesis imperfecta and other causes of osteoporosis in children to reduce the number of fractures, although the long term effects of bisphosphonates in children have not been established. Single doses of bisphosphonates are also used to manage hypercalcaemia, but this treatment should be initiated under specialist advice only.

Pregnancy and Lactation

Pregnancy

Alendronic acid is contraindicated in pregnancy.

There are no adequate data from the use of alendronic acid in pregnant women.

Animal studies suggest possible placenta transfer and effect on skeletal development. As bioavailability of alendronic acid is low and plasma clearance is rapid, clinically significant amounts may not cross the human placenta. However the drug is slowly released from the bone, so that use before pregnancy may result in low level continuous exposure throughout gestation. The use of alendronic acid in women who may become pregnant or during pregnancy is not recommended.

Accidental acute use of individual doses of alendronic acid in the first trimester does not justify for either interruption of the pregnancy or additional diagnostic procedures.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Alendronic acid is contraindicated in breastfeeding.

It is not known whether alendronic acid is excreted into human breast milk. Alendronic acid is poorly absorbed orally, average 1% in adults on an empty stomach, so absorption of alendronate by a breastfeeding infant is unlikely. The molecular weight is low enough to be excreted into breast milk, but low plasma concentrations and rapid plasma clearance suggests that minimal amounts will be excreted into milk.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

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
Duodenal ulcer
Dysgeusia
Dyspepsia
Dysphagia
Episcleritis
Erythema
Fever
Flatulence
Gastric ulceration
Gastritis
Gastro-intestinal perforation
Gastro-intestinal ulceration
Gastrointestinal bleeding
Headache
Hypersensitivity reactions
Hypocalcaemia (symptomatic)
Joint swelling
Malaise
Melaena
Muscle cramps
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

Oral formulations of high strength alendronic acid (70 mg)

Drugs List

Therapeutic Indications

Uses

Treatment of osteoporosis in postmenopausal women to prevent fractures

Dosage

Clinical judgement of the treating physician should guide management plan for each patient based on individual benefit / risk assessment.

Adults

Contraindications

Children under 18 years
Inability to stand or sit upright for at least 30 minutes
Achalasia
Breastfeeding
Delayed oesophageal emptying
Hypocalcaemia
Oesophageal obstruction
Oesophageal strictures
Pregnancy
Renal impairment - glomerular filtration rate below 35ml/minute

Precautions and Warnings

Duodenitis
Dysphagia
Galactosaemia
Gastritis
Gastrointestinal haemorrhage
Glucose-galactose malabsorption syndrome
History of gastrointestinal ulceration
Hypoparathyroidism
Lactose intolerance
Oesophagitis
Peptic ulcer
Upper gastrointestinal surgery
Vitamin D deficiency

Sodium content of effervescent preparation may be significant
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
Some formulations contain hydroxybenzoate
Some formulations contain lactose
Some formulations contain sunset yellow (E110); may cause allergic reaction
Patient must remain upright for at least 30 minutes after dose
Correct disturbances of calcium and mineral metabolism before initiation
Dental check-ups advisable during long-term treatment
Ensure patient's dietary intake of calcium and vitamin D is adequate
Evaluate benefit/risk in long term use ( > 5 years)
Monitor serum calcium levels
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 femoral fracture occurs
Discontinue if symptoms of oesophageal irritation occur
Advise patients to avoid aspirin and NSAID use
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.

Dental examination with appropriate preventative procedures and an individual benefit-risk assessment is recommended prior to bisphosphonate therapy in patients with risk factors for ONJ. While on treatment, patients should avoid invasive dental procedures if possible. Good oral hygiene practices and regular routine dental check-ups should be maintained during treatment with bisphosphonates.

For patients who develop ONJ during treatment, dental surgery may exacerbate the condition. If ONJ occurs during treatment with bisphosphonates, use clinical judgement and guide the management plan of each patient based on individual benefit/risk evaluation. The management plan for patients with ONJ should be set up in close collaboration between the treating physician and a dentist or oral surgeon with expertise in ONJ. Temporary interruption of treatment should be considered until the condition resolves and contributing risk factors are mitigated where possible.

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. Consider discontinuation of bisphosphonate therapy in patients suspected to have an atypical femoral fracture pending an individual risk/benefit assessment. During bisphosphonate therapy, advise patients to report new or unusual thigh, hip or groin pain. Patients presenting with such symptoms should be evaluated for an incomplete femoral fracture.

Alendronic acid is not recommended for children under 18 years of age. A study in a small number of paediatric patients with osteogenesis imperfecta were insufficient to support its use in children. However, some sources suggest that bisphosphonates have been used in the management of severe forms of osteogenesis imperfecta and other causes of osteoporosis in children to reduce the number of fractures, although the long term effects of bisphosphonates in children have not been established. Single doses of bisphosphonates are also used to manage hypercalcaemia, but this treatment should be initiated under specialist advice only.

Pregnancy and Lactation

Pregnancy

Alendronic acid is contraindicated in pregnancy.

There are no adequate data from the use of alendronic acid in pregnant women.

Animal studies suggest possible placenta transfer and effect on skeletal development. As bioavailability of alendronic acid is low and plasma clearance is rapid, clinically significant amounts may not cross the human placenta. However the drug is slowly released from the bone, so that use before pregnancy may result in low level continuous exposure throughout gestation. The use of alendronic acid in women who may become pregnant or during pregnancy is not recommended.

Accidental acute use of individual doses of alendronic acid in the first trimester does not justify for either interruption of the pregnancy or additional diagnostic procedures.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Alendronic acid is contraindicated in breastfeeding.

It is not known whether alendronic acid is excreted into human breast milk. Alendronic acid is poorly absorbed orally, average 1% in adults on an empty stomach, so absorption of alendronate by a breastfeeding infant is unlikely. The molecular weight is low enough to be excreted into breast milk, but low plasma concentrations and rapid plasma clearance suggests that minimal amounts will be excreted into milk.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

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.

The oral solution should be followed by at least 30 ml of plain water.

The effervescent tablet should be dissolved in half a glass of plain water (not less than 120 ml). The solution should be drunk once the fizzing has subsided, followed by at least 30 ml of plain water.

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

Also advise patients 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 patients that failure to follow these instructions may increase their risk of oesophageal problems.

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

Advise patients that if they forget a dose, they should take it the morning after they remember, but they should not take two 70 mg single dose in a single day. Patients should return to the original schedule of one 70 mg single dose once a week on their chosen day.

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

Advise patients not to self medicate with aspirin or ibuprofen.

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
Duodenal ulcer
Dysgeusia
Dyspepsia
Dysphagia
Episcleritis
Erythema
Fever
Flatulence
Gastric ulceration
Gastritis
Gastro-intestinal perforation
Gastro-intestinal ulceration
Gastrointestinal bleeding
Headache
Hypersensitivity reactions
Hypocalcaemia (symptomatic)
Joint swelling
Malaise
Melaena
Muscle cramps
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: September 2015

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.

Summary of Product Characteristics: Alendronic Acid 70mg tablets. Actavis UK Ltd. Revised April 2014.
Summary of Product Characteristics: Alendronic Acid Once Weekly 70mg tablets. Accord Healthcare Ltd. Revised December 2013.
Summary of Product Characteristics: Alendronic Acid 70mg tablets. Wockhardt UK Ltd. Revised July 2014.
Summary of Product Characteristics: Alendronic Acid 70mg tablets. Zentiva. Revised July 2015.
Summary of Product Characteristics: Fosamax Once Weekly 70mg Tablets. Merck Sharp and Dohme Ltd. Revised September 2015.

Summary of Product Characteristics: Binosto 70mg effervescent tablets. Internis Pharmaceuticals Ltd. Revised July 2015.

Summary of Product Characteristics: Alendronic Acid 70mg Oral Solution. Rosemont Pharmaceuticals Ltd. Revised July 2011

MHRA Drug Safety Update July 2008
Available at: https://www.mhra.gov.uk
Last accessed: 09 September 2015

MHRA Drug Safety Update December 2015
Available at: https://www.mhra.gov.uk
Last accessed: 13 January 2016

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 16 August 2017

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: 10 March 2015
Last accessed: 09 September 2015