Drugs List

Therapeutic Indications

Uses

Treatment of osteoporosis in postmenopausal women to reduce the risk of vertebral fractures.
Efficacy in reducing femoral neck fractures has not been demonstrated.

Administration

For oral use.

Take after an overnight fast (at least 6 hours) and 1 hour before the first food or drink (other than water) or other medicinal products/supplements of the day.

Swallow whole with 180 to 240 ml of water while patient is sitting or standing in an upright position.

Patient should not lie down for 1 hour after dose.

N.B. Mineral waters should not be used to take ibandronic acid as they may have a high concentration of calcium.

The tablet should not be sucked or chewed as there is a potential for oropharyngeal ulceration.

Contraindications

Oesophageal abnormalities or factors which delay oesophageal emptying such as stricture or achalasia
Hypocalcaemia
Inability to stand or sit upright for 60 minutes

Pregnancy - see Pregnancy section
Breastfeeding - see Lactation section

Renal impairment - creatinine clearance less than 30ml/min
Children under 18 years

Galactosaemia

Precautions and Warnings

There is limited evidence to support the efficacy of bisphosphonates in elderly women over 80 years.

Correct hypocalcaemia prior to therapy. Other disturbances of bone and mineral metabolism should also treated before therapy is initiated.

Ensure adequate intake of calcium and vitamin D during therapy, through supplements if dietary intake inadequate.

Patients with a history of prolonged oesophageal transit time should pay particular care to the dosing instructions as bisphosphonates have been associated with dysphagia, oesophagitis and oesophageal or gastric ulcers.

Discontinue therapy if signs or symptoms of oesophageal reaction occurs during therapy and advise patients to seek medical attention if they develop symptoms such as new or worsening dysphagia, pain on swallowing, retrosternal pain or heartburn.

Patients should not eat for at least 6 hours prior to dose or 1 hour after dose.
In particular, foods containing calcium (including milk), aluminium, magnesium or iron are likely to affect absorption.

As NSAIDS are associated with gastrointestinal irritation, caution should be taken during concurrent oral medication with ibandronic acid.

Monitor the patient's renal function and serum calcium, phosphate and magnesium levels during treatment.

Osteonecrosis of the jaw has been reported in cancer patients taking bisphosphonate regimens often with concurrent chemotherapy and corticosteroids. These cases have mainly been associated with dental procedures such as tooth extraction and many have shown signs of local infection including osteomyelitis.

Perform dental examination with appropriate preventative procedures prior to ibandronic acid therapy in patients with risk factors (cancer chemotherapy, corticosteroids, poor oral hygiene).

Invasive dental procedures should be avoided in patients taking bisphosphonates. Advise patients to inform their dentist that they are taking bisphosphonates and should not not undergo invasive dental procedures. There is no data available to suggest discontinuation of bisphosphonate treatment prior to dentistry reduces the risk of osteonecrosis of the jaw. Recovery from such procedures is likely to be prolonged.

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 stress fractures of the proximal femoral shaft with poor healing have been reported for treatment with another bisphosphonate, alendronic acid. Limited data exists regarding a relationship for other bisphosphonates and atypical stress fractures. However, the possibility of atypical stress fractures cannot be excluded. Patients who develop atypical stress fractures should discontinue treatment and receive no further bisphosphonate treatment.

Tablets contain lactose. Contraindicated in patients with galactosaemia and must be prescribed with caution to patients with glucose-galactose malabsorption syndrome or lactose intolerance.

CSM Warnings

The CHM recommends the following:

Atypical stress fractures of the proximal femoral shaft with poor healing have been reported rarely with long-term bisphosphonate treatment;

Patients should be re-evaluated periodically based on an assessment of the benefits and risks of the bisphosphonate treatment, especially after 5 years or more of treatment;

Patients should report any thigh, hip or groin pain during treatment with a bisphosphonate;

Discontinuation of bisphosphonate treatment in patients suspected to have an atypical femoral fracture should be considered after an assessment of the benefits and risks of continued treatment.

Pregnancy and Lactation

Pregnancy

Not recommended for use during pregnancy.

Animal studies have shown reproduction toxicological effects and although the significance to humans is unknown, ibandronic acid should not be used in human pregnancy. If exposure occurs during gestation, detailed ultrasound examination of the foetal skeleton appears to be warranted (Briggs, 2011) although Schaeffer (2007) states that accidental use of a single dose does not justify interruption of the pregnancy or additional diagnostic procedures.

There are no adequate reproductive studies in humans. Animal studies have shown some evidence of reproductive toxicity and effects on skeletal development. Briggs (2011) states that the amount of drug retained in the bone and eventually released back into systemic circulation is directly related to the dose and duration of treatment and that ibandronate probably crosses the placenta, treatment of the mother before conception could result in continuous exposure of the embryo and foetus to an unknown amount of the drug. Therefore treatment with ibandronic acid in women who may become pregnant or during pregnancy is not recommended.

However Schaeffer (2007) states accidental acute use of individual doses in the first trimester does not justify 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 14-17 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 at ( https://www.toxbase.org/ ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Licensed in pregnancy? - No, contraindicated

Recommended for use in pregnancy? - No

Known human teratogen? - Unknown

Lactation

Women should not breast feed during therapy.

It is unknown if ibandronic acid is excreted in breast milk, however Briggs (2011) suggests that with a molecular weight of around 318 (for the free acid), prolonged elimination half life and lack of metabolism that the active drug will be excreted in breast milk. Animal studies have shown the presence of low levels of ibandronic acid in rat milk following intravenous administration.

The low oral bioavailability of ibandronic acid (less than 1% fasting, lower with food) and the fact that it binds to calcium in milk make it likely that the amount absorbed by a nursing infant would be insignificant.

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

Drug excreted in breast milk? - Unknown - a low molecular weight, long elimination half life and lack of metabolism suggest it is possible.

Considered suitable or recommended by manufacturer? - No

Side Effects

Dyspepsia
Nausea
Abdominal pain
Diarrhoea
Flatulence
Gastroesophageal reflux disease
Headache
Influenza-like symptoms
Fatigue
Myalgia
Arthralgia
Rash
Muscle cramps
Musculoskeletal pain
Stiffness
Vomiting
Gastritis
Oesophageal ulceration
Oesophageal stricture
Duodenitis
Hypersensitivity reactions
Angioedema
Facial oedema
Urticaria
Dizziness
Oesophagitis
Fever
Chills
Decreased appetite
Bone pain
Dysphagia
Back pain
Anaemia
Bronchospasm
Taste disturbances
Paraesthesia
Azotaemia
Ocular inflammation
Osteonecrosis (primarily of the jaw)
Atypical femoral fracture
Hypocalcaemia
Hypophosphataemia
Pharyngitis
Asthenia
Pruritus
Gastric ulceration
Duodenal ulcer
Uveitis
Episcleritis
Scleritis
Stevens-Johnson syndrome
Erythema multiforme
Bullous dermatoses
Osteonecrosis of the external auditory canal

Presentation

Tablets containing 150mg ibandronic acid (as ibandronic sodium monohydrate).

Drugs List

Therapeutic Indications

Uses

Treatment of osteoporosis in postmenopausal women to reduce the risk of vertebral fractures.
Efficacy in reducing femoral neck fractures has not been demonstrated.

Dosage

Adults

Children

Patients with Renal Impairment

Additional Dosage Information

Administration

For oral use.

Take after an overnight fast (at least 6 hours) and 1 hour before the first food or drink (other than water) or other medicinal products/supplements of the day.

Swallow whole with 180 to 240 ml of water while patient is sitting or standing in an upright position.

Patient should not lie down for 1 hour after dose.

N.B. Mineral waters should not be used to take ibandronic acid as they may have a high concentration of calcium.

The tablet should not be sucked or chewed as there is a potential for oropharyngeal ulceration.

Contraindications

Oesophageal abnormalities or factors which delay oesophageal emptying such as stricture or achalasia
Hypocalcaemia
Inability to stand or sit upright for 60 minutes

Pregnancy - see Pregnancy section
Breastfeeding - see Lactation section

Renal impairment - creatinine clearance less than 30ml/min
Children under 18 years

Galactosaemia

Precautions and Warnings

There is limited evidence to support the efficacy of bisphosphonates in elderly women over 80 years.

Correct hypocalcaemia prior to therapy. Other disturbances of bone and mineral metabolism should also treated before therapy is initiated.

Ensure adequate intake of calcium and vitamin D during therapy, through supplements if dietary intake inadequate.

Patients with a history of prolonged oesophageal transit time should pay particular care to the dosing instructions as bisphosphonates have been associated with dysphagia, oesophagitis and oesophageal or gastric ulcers.

Discontinue therapy if signs or symptoms of oesophageal reaction occurs during therapy and advise patients to seek medical attention if they develop symptoms such as new or worsening dysphagia, pain on swallowing, retrosternal pain or heartburn.

Patients should not eat for at least 6 hours prior to dose or 1 hour after dose.
In particular, foods containing calcium (including milk), aluminium, magnesium or iron are likely to affect absorption.

As NSAIDS are associated with gastrointestinal irritation, caution should be taken during concurrent oral medication with ibandronic acid.

Monitor the patient's renal function and serum calcium, phosphate and magnesium levels during treatment.

Osteonecrosis of the jaw has been reported in cancer patients taking bisphosphonate regimens often with concurrent chemotherapy and corticosteroids. These cases have mainly been associated with dental procedures such as tooth extraction and many have shown signs of local infection including osteomyelitis.

Perform dental examination with appropriate preventative procedures prior to ibandronic acid therapy in patients with risk factors (cancer chemotherapy, corticosteroids, poor oral hygiene).

Invasive dental procedures should be avoided in patients taking bisphosphonates. Advise patients to inform their dentist that they are taking bisphosphonates and should not not undergo invasive dental procedures. There is no data available to suggest discontinuation of bisphosphonate treatment prior to dentistry reduces the risk of osteonecrosis of the jaw. Recovery from such procedures is likely to be prolonged.

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 stress fractures of the proximal femoral shaft with poor healing have been reported for treatment with another bisphosphonate, alendronic acid. Limited data exists regarding a relationship for other bisphosphonates and atypical stress fractures. However, the possibility of atypical stress fractures cannot be excluded. Patients who develop atypical stress fractures should discontinue treatment and receive no further bisphosphonate treatment.

Tablets contain lactose. Contraindicated in patients with galactosaemia and must be prescribed with caution to patients with glucose-galactose malabsorption syndrome or lactose intolerance.

CSM Warnings

The CHM recommends the following:

Atypical stress fractures of the proximal femoral shaft with poor healing have been reported rarely with long-term bisphosphonate treatment;

Patients should be re-evaluated periodically based on an assessment of the benefits and risks of the bisphosphonate treatment, especially after 5 years or more of treatment;

Patients should report any thigh, hip or groin pain during treatment with a bisphosphonate;

Discontinuation of bisphosphonate treatment in patients suspected to have an atypical femoral fracture should be considered after an assessment of the benefits and risks of continued treatment.

Pregnancy and Lactation

Pregnancy

Not recommended for use during pregnancy.

Animal studies have shown reproduction toxicological effects and although the significance to humans is unknown, ibandronic acid should not be used in human pregnancy. If exposure occurs during gestation, detailed ultrasound examination of the foetal skeleton appears to be warranted (Briggs, 2011) although Schaeffer (2007) states that accidental use of a single dose does not justify interruption of the pregnancy or additional diagnostic procedures.

There are no adequate reproductive studies in humans. Animal studies have shown some evidence of reproductive toxicity and effects on skeletal development. Briggs (2011) states that the amount of drug retained in the bone and eventually released back into systemic circulation is directly related to the dose and duration of treatment and that ibandronate probably crosses the placenta, treatment of the mother before conception could result in continuous exposure of the embryo and foetus to an unknown amount of the drug. Therefore treatment with ibandronic acid in women who may become pregnant or during pregnancy is not recommended.

However Schaeffer (2007) states accidental acute use of individual doses in the first trimester does not justify 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 14-17 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 at ( https://www.toxbase.org/ ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Licensed in pregnancy? - No, contraindicated

Recommended for use in pregnancy? - No

Known human teratogen? - Unknown

Lactation

Women should not breast feed during therapy.

It is unknown if ibandronic acid is excreted in breast milk, however Briggs (2011) suggests that with a molecular weight of around 318 (for the free acid), prolonged elimination half life and lack of metabolism that the active drug will be excreted in breast milk. Animal studies have shown the presence of low levels of ibandronic acid in rat milk following intravenous administration.

The low oral bioavailability of ibandronic acid (less than 1% fasting, lower with food) and the fact that it binds to calcium in milk make it likely that the amount absorbed by a nursing infant would be insignificant.

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

Drug excreted in breast milk? - Unknown - a low molecular weight, long elimination half life and lack of metabolism suggest it is possible.

Considered suitable or recommended by manufacturer? - No

Effects on Ability to Drive and Operate Machinery

No effects known. However side effects such as dizziness have been reported and must be taken into consideration prior to driving or operating any machinery.

Counselling

Advise patients to discontinue treatment and seek medical attention if they develop symptoms of oesophageal reaction such as; new or worsening dysphagia, pain on swallowing, retrosternal pain or heartburn.

Advise patient to ensure adequate calcium and vitamin D intake.

Patients must follow the dose instructions carefully.

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

Advise patients to inform their dentist that they are taking bisphosphonates and should not undergo invasive dental procedures.

Advise patients to report any new thigh, hip or groin pain during treatment with ibandronic acid.

Advise patient not to eat at least 6 hours prior and 30 minutes following tablet, to take the tablet with a full glass of water and not to lie down for 60 minutes after the dose has been taken ( see Administration ).

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

Side Effects

Dyspepsia
Nausea
Abdominal pain
Diarrhoea
Flatulence
Gastroesophageal reflux disease
Headache
Influenza-like symptoms
Fatigue
Myalgia
Arthralgia
Rash
Muscle cramps
Musculoskeletal pain
Stiffness
Vomiting
Gastritis
Oesophageal ulceration
Oesophageal stricture
Duodenitis
Hypersensitivity reactions
Angioedema
Facial oedema
Urticaria
Dizziness
Oesophagitis
Fever
Chills
Decreased appetite
Bone pain
Dysphagia
Back pain
Anaemia
Bronchospasm
Taste disturbances
Paraesthesia
Azotaemia
Ocular inflammation
Osteonecrosis (primarily of the jaw)
Atypical femoral fracture
Hypocalcaemia
Hypophosphataemia
Pharyngitis
Asthenia
Pruritus
Gastric ulceration
Duodenal ulcer
Uveitis
Episcleritis
Scleritis
Stevens-Johnson syndrome
Erythema multiforme
Bullous dermatoses
Osteonecrosis of the external auditory canal

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 ).

Shelf Life and Storage

No special storage instructions.

Further Information

Last Full Review Date: March 2012

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.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Summary of Product Characteristics: Bonviva 150mg Film-Coated tablets. Roche Products Ltd. Revised May 2015.

Summary of Product Characteristics: Quodixor 150mg Film-Coated tablets. Aspire Pharma. Revised February 2012.

MHRA Drug Safety Update: Volume 2 Issue 8, March 2009
https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON041211
Last Accessed: 25/01/2010

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: 17 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
Ibandronate Last revised: 4, January 2011
Last accessed: 12, March 2012