Drugs List

Therapeutic Indications

Uses

Treatment of osteoporosis in postmenopausal women to prevent fractures

Treatment of osteoporosis in postmenopausal women in order to reduce the risk of fractures; efficacy on vertebral fractures has been demonstrated, but not on femoral neck fractures.

Administration

For intravenous injection only.

Other routes of administration are hazardous and may cause tissue damage.

Contraindications

Children under 18 years
Breastfeeding
Hypocalcaemia
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute

Precautions and Warnings

Risk of cardiac failure

Avoid overhydration in patients at risk of cardiac failure
Consider a dental exam & appropriate preventive dentistry before treatment
Ensure adequate vitamin D and calcium supplementation
Resuscitation facilities must be immediately available
Correct disturbances of calcium and mineral metabolism before initiation
Monitor renal function in patients with risk factors for renal impairment
Advise patient to report any ear pain, discharge or infection
Advise patient to report any new thigh, hip or groin pain
Consider osteonecrosis of external auditory canal if ear symptoms occur
Consider discontinuation if atypical femoral fracture occurs
Consider withholding treatment if osteonecrosis of the jaw occurs
Advise patient of need for high oral hygiene standards
Give patient package leaflet and patient reminder card
Patient to inform dentist of bisphosphonate use: avoid invasive procedures

Ibandronic acid, like other bisphosphonates administered intravenously, may cause transient decrease in serum calcium levels. Existing hypocalcaemia must be corrected before starting treatment.

Osteonecrosis of the jaw (ONJ) has been reported rarely in patients taking ibandronic acid, 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. Additional risk factors for ONJ include smoking, anaemia, coagulopathies, poor oral hygiene and concomitant treatment with corticosteroids, chemotherapy, angiogenesis inhibitors and radiotherapy to the head and neck.

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 fractures of the femur have been reported in patients receiving bisphosphonate therapy, particularly in patients receiving long-term osteoporosis treatment. Atypical femoral fractures may be associated with thigh or groin pain; any patient presenting or reporting such symptoms should be examined for fracture in both femurs, as fractures are often bilateral.

Pregnancy and Lactation

Pregnancy

Ibandronic acid is contraindicated in pregnancy.

There are no adequate reproductive studies in humans. Animal studies have shown reproductive toxicity and effects on skeletal development, and although the significance to humans is unknown, ibandronic acid should not be used in human pregnancy. The manufacturer states that ibandronic acid should not be used during pregnancy.

Briggs (2015) states that ibandronic acid probably crosses the placenta, and 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, therefore treatment of the mother before conception could result in continuous exposure of the embryo and foetus to an unknown amount of the drug. Uptake of ibandronic acid is also thought to be higher in fetal bone than in maternal bone. However, Schaeffer (2015) states that accidental use of a single dose does not justify interruption of the pregnancy or additional diagnostic procedures.

If exposure occurs during gestation, detailed ultrasound examination of the foetal skeleton appears to be warranted, and infants exposed to ibandronic acid in utero should be monitored for hypocalcemia during the first few days after birth (Briggs, 2015).

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

Ibandronic acid is contraindicated in breastfeeding.

It is unknown if ibandronic acid is excreted in breast milk, however Briggs (2015) states that a low molecular weight, prolonged elimination half life and lack of metabolism means that the active drug is likely to be excreted in breast milk. Animal studies have shown the presence of low levels of ibandronic acid in rat milk following intravenous administration. The use of ibandronic acid in breastfeeding is contraindicated by the manufacturer.

The low oral bioavailability of ibandronic acid and it's high calcium binding in milk may limit absorption of the active drug by a nursing infant (Briggs, 2015).

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 pain
Anaphylactic reaction
Anaphylactic shock
Angioedema
Arthralgia
Asthenia
Atypical femoral fracture
Back pain
Bone pain
Bullous dermatoses
Chills
Constipation
Decreased appetite
Diarrhoea
Dyspepsia
Episcleritis
Erythema multiforme
Exacerbation of pre-existing asthma
Facial oedema
Fatigue
Fever
Gastritis
Headache
Hypersensitivity reactions
Influenza-like symptoms
Injection site reactions
Musculoskeletal pain
Myalgia
Nausea
Ocular inflammation
Osteonecrosis (primarily of the jaw)
Osteonecrosis of the external auditory canal
Phlebitis
Rash
Scleritis
Stevens-Johnson syndrome
Thrombophlebitis
Urticaria
Uveitis

Presentation

Injections of ibandronic acid.

Drugs List

Therapeutic Indications

Uses

Treatment of osteoporosis in postmenopausal women to prevent fractures

Treatment of osteoporosis in postmenopausal women in order to reduce the risk of fractures; efficacy on vertebral fractures has been demonstrated, but not on femoral neck fractures.

Dosage

Adults

Additional Dosage Information

Administration

For intravenous injection only.

Other routes of administration are hazardous and may cause tissue damage.

Contraindications

Children under 18 years
Breastfeeding
Hypocalcaemia
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute

Precautions and Warnings

Risk of cardiac failure

Avoid overhydration in patients at risk of cardiac failure
Consider a dental exam & appropriate preventive dentistry before treatment
Ensure adequate vitamin D and calcium supplementation
Resuscitation facilities must be immediately available
Correct disturbances of calcium and mineral metabolism before initiation
Monitor renal function in patients with risk factors for renal impairment
Advise patient to report any ear pain, discharge or infection
Advise patient to report any new thigh, hip or groin pain
Consider osteonecrosis of external auditory canal if ear symptoms occur
Consider discontinuation if atypical femoral fracture occurs
Consider withholding treatment if osteonecrosis of the jaw occurs
Advise patient of need for high oral hygiene standards
Give patient package leaflet and patient reminder card
Patient to inform dentist of bisphosphonate use: avoid invasive procedures

Ibandronic acid, like other bisphosphonates administered intravenously, may cause transient decrease in serum calcium levels. Existing hypocalcaemia must be corrected before starting treatment.

Osteonecrosis of the jaw (ONJ) has been reported rarely in patients taking ibandronic acid, 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. Additional risk factors for ONJ include smoking, anaemia, coagulopathies, poor oral hygiene and concomitant treatment with corticosteroids, chemotherapy, angiogenesis inhibitors and radiotherapy to the head and neck.

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 fractures of the femur have been reported in patients receiving bisphosphonate therapy, particularly in patients receiving long-term osteoporosis treatment. Atypical femoral fractures may be associated with thigh or groin pain; any patient presenting or reporting such symptoms should be examined for fracture in both femurs, as fractures are often bilateral.

Pregnancy and Lactation

Pregnancy

Ibandronic acid is contraindicated in pregnancy.

There are no adequate reproductive studies in humans. Animal studies have shown reproductive toxicity and effects on skeletal development, and although the significance to humans is unknown, ibandronic acid should not be used in human pregnancy. The manufacturer states that ibandronic acid should not be used during pregnancy.

Briggs (2015) states that ibandronic acid probably crosses the placenta, and 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, therefore treatment of the mother before conception could result in continuous exposure of the embryo and foetus to an unknown amount of the drug. Uptake of ibandronic acid is also thought to be higher in fetal bone than in maternal bone. However, Schaeffer (2015) states that accidental use of a single dose does not justify interruption of the pregnancy or additional diagnostic procedures.

If exposure occurs during gestation, detailed ultrasound examination of the foetal skeleton appears to be warranted, and infants exposed to ibandronic acid in utero should be monitored for hypocalcemia during the first few days after birth (Briggs, 2015).

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

Ibandronic acid is contraindicated in breastfeeding.

It is unknown if ibandronic acid is excreted in breast milk, however Briggs (2015) states that a low molecular weight, prolonged elimination half life and lack of metabolism means that the active drug is likely to be excreted in breast milk. Animal studies have shown the presence of low levels of ibandronic acid in rat milk following intravenous administration. The use of ibandronic acid in breastfeeding is contraindicated by the manufacturer.

The low oral bioavailability of ibandronic acid and it's high calcium binding in milk may limit absorption of the active drug by a nursing infant (Briggs, 2015).

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 pain
Anaphylactic reaction
Anaphylactic shock
Angioedema
Arthralgia
Asthenia
Atypical femoral fracture
Back pain
Bone pain
Bullous dermatoses
Chills
Constipation
Decreased appetite
Diarrhoea
Dyspepsia
Episcleritis
Erythema multiforme
Exacerbation of pre-existing asthma
Facial oedema
Fatigue
Fever
Gastritis
Headache
Hypersensitivity reactions
Influenza-like symptoms
Injection site reactions
Musculoskeletal pain
Myalgia
Nausea
Ocular inflammation
Osteonecrosis (primarily of the jaw)
Osteonecrosis of the external auditory canal
Phlebitis
Rash
Scleritis
Stevens-Johnson syndrome
Thrombophlebitis
Urticaria
Uveitis

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: February 2018

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: Bonviva 3mg/3ml solution for injection in pre-filled syringe. Roche Products Ltd. Revised April 2016.

Summary of Product Characteristics: Ibandronic Acid 3mgl Solution for Injection in pre-filled syringe. Accord Healthcare Ltd. Revised September 2017.

Summary of Product Characteristics: Ibandronic Acid 3mg/3ml Solution for Injection. Teva UK Ltd. Revised December 2016.

Summary of Product Characteristics: Ibandronic Acid 3mg/3ml Solution for Injection. Actavis UK Ltd. Revised May 2015.