Drugs List

Therapeutic Indications

Uses

Prevention of skeletal events (pathological fractures, bone complications requiring radiotherapy or surgery) in patients with breast cancer and bone metastases.

Administration

For oral use.

Take dose after an overnight fast (at least 6 hours) and before the first food or drink of the day. Avoid medicinal products or supplements (including calcium) before taking ibandronic acid tablets. Fast for another 30 minutes after administration.

Swallow tablets whole with 180 to 240ml plain water whilst standing or sitting in an upright position.
Take with plain water only. Note that some mineral waters have higher concentrations of calcium and so should not be used.

The patient should not lie down for 60 minutes after taking tablet.

Tablets should not be sucked or chewed because of a potential for oropharyngeal ulceration.

Contraindications

Children under 18 years

Pregnancy - see Pregnancy section

Breastfeeding - see Lactation section

Hypocalcaemia

Oesophageal stricture or achalasia

Ibandronic acid tablets are contraindicated in patients unable to stand or sit upright for 60 minutes

Galactosaemia

Precautions and Warnings

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

Hypocalcaemia and other bone and mineral metabolism disturbances should be corrected before treatment for metastatic bone disease. Ensure adequate intake of calcium and vitamin D for all patients (supplements may be required).

Oral bisphosphonates have been associated with dysphagia, oesophagitis and oesophageal or gastric ulcers. Advise patients to follow the dosing instructions closely.

Discontinue ibandronic acid treatment if signs or symptoms indicate a possible oesophageal reaction such as oesophageal irritation, new or worsening dysphagia, pain on swallowing, retrosternal pain or heartburn.

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

Renal function, serum calcium, serum phosphate and serum magnesium must be closely monitored during treatment.

Clinical studies involving long term treatment with ibandronic acid have not shown any evidence of deterioration in renal function.

Renal impairment - see Dosage - Renal impairment.

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 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.

Ibandronic acid tablets contain lactose and should therefore not be administered in patients with rare hereditary problems of galactose intolerance, glucose-galactose malabsorption 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 as 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 that 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 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

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

Side Effects

Hypocalcaemia
Dyspepsia
Nausea
Abdominal pain
Oesophagitis
Asthenia
Anaemia
Dysgeusia
Paraesthesia
Dry mouth
Gastro-intestinal haemorrhage
Dysphagia
Gastritis
Pruritus
Azotaemia
Chest pain
Influenza-like syndrome
Malaise
Pain
Hyperparathyroidism
Osteonecrosis (primarily of the jaw)
Gastric ulceration
Duodenal ulcer
Ocular inflammation
Uveitis
Episcleritis
Scleritis
Hypophosphataemia
Diarrhoea
Vomiting
Headache
Angioedema
Pharyngitis
Atypical femoral fracture
Osteonecrosis of the external auditory canal

Other side effects reported with other bisphosphonates include:

Constipation
Exacerbation of existing gastrointestinal problems
Myalgia
Hypersensitivity reactions
Rash
Leucopenia
Fever
Urticaria

Presentation

Tablets containing 50mg ibandronic acid (as ibandronate sodium monohydrate).

Drugs List

Therapeutic Indications

Uses

Prevention of skeletal events (pathological fractures, bone complications requiring radiotherapy or surgery) in patients with breast cancer and bone metastases.

Dosage

Treatment should only be initiated by physicians experienced in the treatment of cancer.

Adults

Children

Patients with Renal Impairment

Administration

For oral use.

Take dose after an overnight fast (at least 6 hours) and before the first food or drink of the day. Avoid medicinal products or supplements (including calcium) before taking ibandronic acid tablets. Fast for another 30 minutes after administration.

Swallow tablets whole with 180 to 240ml plain water whilst standing or sitting in an upright position.
Take with plain water only. Note that some mineral waters have higher concentrations of calcium and so should not be used.

The patient should not lie down for 60 minutes after taking tablet.

Tablets should not be sucked or chewed because of a potential for oropharyngeal ulceration.

Contraindications

Children under 18 years

Pregnancy - see Pregnancy section

Breastfeeding - see Lactation section

Hypocalcaemia

Oesophageal stricture or achalasia

Ibandronic acid tablets are contraindicated in patients unable to stand or sit upright for 60 minutes

Galactosaemia

Precautions and Warnings

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

Hypocalcaemia and other bone and mineral metabolism disturbances should be corrected before treatment for metastatic bone disease. Ensure adequate intake of calcium and vitamin D for all patients (supplements may be required).

Oral bisphosphonates have been associated with dysphagia, oesophagitis and oesophageal or gastric ulcers. Advise patients to follow the dosing instructions closely.

Discontinue ibandronic acid treatment if signs or symptoms indicate a possible oesophageal reaction such as oesophageal irritation, new or worsening dysphagia, pain on swallowing, retrosternal pain or heartburn.

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

Renal function, serum calcium, serum phosphate and serum magnesium must be closely monitored during treatment.

Clinical studies involving long term treatment with ibandronic acid have not shown any evidence of deterioration in renal function.

Renal impairment - see Dosage - Renal impairment.

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 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.

Ibandronic acid tablets contain lactose and should therefore not be administered in patients with rare hereditary problems of galactose intolerance, glucose-galactose malabsorption 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 as 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 that 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 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

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

Effects on Ability to Drive and Operate Machinery

No studies on the effects of ibandronic acid on the ability to drive and use machines have been performed.

Counselling

Advise patient not to eat for 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 patients to stop tablets and seek medical advice if symptoms indicate a possible oesophageal reaction such as oesophageal irritation, new or worsening dysphagia, pain on swallowing, retrosternal pain or heartburn.

Advise patients to maintain adequate oral hygiene during and after treatment with bisphosphonates. Remind patients to advise their dentist that they are taking a bisphosphonate.

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 to report any ear pain, discharge or infection.

Side Effects

Hypocalcaemia
Dyspepsia
Nausea
Abdominal pain
Oesophagitis
Asthenia
Anaemia
Dysgeusia
Paraesthesia
Dry mouth
Gastro-intestinal haemorrhage
Dysphagia
Gastritis
Pruritus
Azotaemia
Chest pain
Influenza-like syndrome
Malaise
Pain
Hyperparathyroidism
Osteonecrosis (primarily of the jaw)
Gastric ulceration
Duodenal ulcer
Ocular inflammation
Uveitis
Episcleritis
Scleritis
Hypophosphataemia
Diarrhoea
Vomiting
Headache
Angioedema
Pharyngitis
Atypical femoral fracture
Osteonecrosis of the external auditory canal

Other side effects reported with other bisphosphonates include:

Constipation
Exacerbation of existing gastrointestinal problems
Myalgia
Hypersensitivity reactions
Rash
Leucopenia
Fever
Urticaria

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

Store in the original packaging
Protect from moisture

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.

Summary of Product Characteristics: Bondronat 50mg Film-coated Tablets. Roche Products Ltd. Revised July 2011.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

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

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