Chemical formula: C₉H₂₃NO₇P₂ Molecular mass: 319.229 g/mol PubChem compound: 60852
Ibandronic acid interacts in the following cases:
For patients with moderate renal impairment (CLcr ≥30 and <50 mL/min) or severe renal impairment (CLcr <30 mL/min) being treated for the prevention of skeletal events in patients with breast cancer and metastatic bone disease the following dosing recommendations should be followed (see section 5.2):
| Creatinine Clearance (ml/min) | Dosage | Infusion Volume1 and Time2 |
|---|---|---|
| >50 CLcr <80 | 6 mg (6 ml of concentrate for solution for infusion) | 100 ml over 15 minutes |
| >30 CLcr <50 | 4 mg (4 ml of concentrate for solution for infusion) | 500 ml over 1 hour |
| <30 | 2 mg (2 ml of concentrate for solution for infusion) | 500 ml over 1 hour |
1 0.9% sodium chloride solution or 5% glucose solution
2 Administration every 3 to 4 week
A 15 minute infusion time has not been studied in cancer patients with CLCr <50 mL/min.
In healthy male volunteers and postmenopausal women, intravenous ranitidine caused an increase in ibandronic acid bioavailability of about 20% (which is within the normal variability of the bioavailability of ibandronic acid), probably as a result of reduced gastric acidity. However, no dosage adjustment is required when ibandronic acid is administered with H2-antagonists or medicinal products that increase gastric pH.
Caution is advised when bisphosphonates are administered with aminoglycosides, since both substances can lower serum calcium levels for prolonged periods. Attention should also be paid to the possible existence of simultaneous hypomagnesaemia.
There are no data on the effects of ibandronic acid in humans. In reproductive studies in rats by the oral route, ibandronic acid decreased fertility. In studies in rats using the intravenous route, ibandronic acid decreased fertility at high daily doses.
Since Acetylsalicylic acid, Nonsteroidal Anti-Inflammatory medicinal products (NSAIDs) and bisphosphonates are associated with gastrointestinal irritation, caution should be taken during concomitant administration.
Cases of anaphylactic reaction/shock, including fatal events, have been reported in patients treated with IV ibandronic acid. Appropriate medical support and monitoring measures should be readily available when Bondronat intravenous injection is administered. If anaphylactic or other severe hypersensitivity/allergic reactions occur, immediately discontinue the injection and initiate appropriate treatment.
Osteonecrosis of the external auditory canal has been reported with bisphosphonates, mainly in association with long-term therapy. Possible risk factors for osteonecrosis of the external auditory canal include steroid use and chemotherapy and/or local risk factors such 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.
Orally administered bisphosphonates may cause local irritation of the upper gastrointestinal mucosa. Because of these possible irritant effects and a potential for worsening of the underlying disease, caution should be used when ibandronic acid is given to patients with active upper gastrointestinal problems (e.g. known Barrett’s oesophagus, dysphagia, other oesophageal diseases, gastritis, duodenitis or ulcers).
Adverse experiences such as oesophagitis, oesophageal ulcers and oesophageal erosions, in some cases severe and requiring hospitalization, rarely with bleeding or followed by oesophageal stricture or perforation, have been reported in patients receiving treatment with oral bisphosphonates. The risk of severe oesophageal adverse experiences appears to be greater in patients who do not comply with the dosing instruction and/or who continue to take oral bisphosphonates after developing symptoms suggestive of oesophageal irritation. Patients should pay particular attention and be able to comply with the dosing instructions.
Physicians should be alert to any signs or symptoms signaling a possible oesophageal reaction and patients should be instructed to discontinue ibandronic acid and seek medical attention if they develop dysphagia, odynophagia, retrosternal pain or new or worsening heartburn.
While no increased risk was observed in controlled clinical trials there have been post-marketing reports of gastric and duodenal ulcers with oral bisphosphonate use, some severe and with complications.
Osteonecrosis of the jaw (ONJ) has been reported very rarely in the post marketing setting in patients receiving ibandronic acid for oncology indications.
The start of treatment or of a new course of treatment should be delayed in patients with unhealed open soft tissue lesions in the mouth.
A dental examination with preventive dentistry and an individual benefit-risk assessment is recommended prior to treatment with ibandronic acid in patients with concomitant risk factors.
The following risk factors should be considered when evaluating a patient’s risk of developing ONJ:
All patients should be encouraged to maintain good oral hygiene, undergo routine dental check-ups, and immediately report any oral symptoms such as dental mobility, pain or swelling, or non-healing of sores or discharge during treatment with ibandronic acid. While on treatment, invasive dental procedures should be performed only after careful consideration and be avoided in close proximity to ibandronic acid administration.
The management plan of the patients who develop 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 ibandronic acid treatment should be considered until the condition resolves and contributing risk factors are mitigated where possible.
There are no adequate data from the use of ibandronic acid in pregnant women. Studies in rats have shown reproductive toxicity. The potential risk for humans is unknown. Therefore, ibandronic acid should not be used during pregnancy.
It is not known whether ibandronic acid is excreted in human milk. Studies in lactating rats have demonstrated the presence of low levels of ibandronic acid in the milk following intravenous administration. Ibandronic acid should not be used during lactation.
There are no data on the effects of ibandronic acid in humans. In reproductive studies in rats by the oral route, ibandronic acid decreased fertility. In studies in rats using the intravenous route, ibandronic acid decreased fertility at high daily doses.
On the basis of the pharmacodynamic and pharmacokinetic profile and reported adverse reactions, it is expected that ibandronic acid has no or negligible influence on the ability to drive and use machines.
The most serious reported adverse reactions are anaphylactic reaction/shock, atypical fractures of the femur, osteonecrosis of the jaw, gastrointestinal irritation, and ocular inflammation.Treatment was most frequently associated with a decrease in serum calcium to below normal range (hypocalcaemia), followed by dyspepsia.
Listed below are the adverse reactions from 2 pivotal phase III studies (Prevention of skeletal events in patients with breast cancer and bone metastases: 286 patients treated with ibandronic acid 50 mg administered orally), and from post-marketing experience.
Adverse reactions are listed according to MedDRA system organ class and frequency category. Frequency categories are defined using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000),very rare (<1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Adverse Drug Reactions Reported for Oral Administration of Ibandronic acid:
Uncommon: Anaemia
Very rare: Hypersensitivity†, bronchospasm†, angioedema†, Anaphylactic reaction/shock†**
Not known: Asthma exacerbation
Common: Hypocalcaemia**
Uncommon: Paraesthesia, dysgeusia (taste perversion)
Rare: Ocular inflammation†**
Common: Oesophagitis, abdominal pain, dyspepsia, nausea
Uncommon: Haemorrage, duodenal ulcer, gastritis, dysphagia, dry mouth
Uncommon: Pruritus
Very rare: Stevens-Johnson Syndrome†, Erythema Multiforme†, Dermatitis Bullous†
Rare: Atypical subtrochanteric and diaphyseal femoral fractures†
Very rare: Osteonecrosis of jaw†**, Osteonecrosis of the external auditory canal (bisphosphonate class adverse reaction)†
Uncommon: Azotaemia (uraemia)
Common: Asthenia
Uncommon: Chest pain, influenza-like illness, malaise, pain
Uncommon: Blood parathyroid hormone increased
** See further information below
† Identified in post-marketing experience
The most serious reported adverse reactions are anaphylactic reaction/shock, atypical fractures of the femur, osteonecrosis for the jaw and ocular inflammation.
Treatment of tumour induced hypercalcaemia is most frequently associated with a rise in body temperature. Less frequently, a decrease in serum calcium below normal range (hypocalcaemia) is reported. In most cases no specific treatment was required and the symptoms subsided after a couple of hours/days.
In the prevention of skeletal events in patients with breast cancer and bone metastases, treatment is most frequently associated with asthenia followed by rise in body temperature and headache.
Listed below are the adverse drug reactions from the pivotal phase III studies (Treatment of tumour induced hypercalcaemia: 311 patients treated with ibandronic acid 2 mg or 4 mg; Prevention of skeletal events in patients with breast cancer and bone metastases: 152 patients treated with ibandronic acid 6 mg), and from post-marketing experience.
Adverse reactions are listed according to MedDRA system organ class and frequency category. Frequency categories are defined using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Adverse Reactions Reported for Intravenous Administration of Ibandronic acid:
Common: Infection
Uncommon: Cystitis, vaginitis, oral candidiasis
Uncommon: Benign skin neoplasm
Uncommon: Anaemia, blood dyscrasia
Very rare: Hypersensitivity†, bronchospasm†, angioedema†, anaphylactic reaction/shock†**
Not known: Asthma exacerbation
Common: Parathyroid disorder
Common: Hypocalcaemia**
Uncommon: Hypophosphataemia
Uncommon: Sleep disorder, anxiety, affection lability
Common: Headache, dizziness, dysgeusia (taste perversion)
Uncommon: Cerebrovascular disorder, nerve root lesion, amnesia, migraine, neuralgia, hypertonia, hyperaestesia, paraesthesia circumoral, parosmia
Common: Cataract
Rare: Ocular inflammation†**
Uncommon: Deafness
Common: Bundle branch block
Uncommon: Myocardial ischaemia, cardiovascular disorder, palpitations
Common: Pharyngitis
Uncommon: Lung oedema, stridor
Common: Diarrhoea, vomiting, dyspepsia, gastrointestinal pain, tooth disorder
Uncommon: Gastroenteritis, gastritis, mouth ulceration, dysphagia, cheilitis
Uncommon: Cholelithiasis
Common: Skin disorder, ecchymosis
Uncommon: Rash, alopecia
Very rare: Stevens-Johnson Syndrome†, Erythema Multiforme†, Dermatitis Bullous†
Common: Osteoarthritis, myalgia, arthralgia, joint disorder, bone pain
Rare: Atypical subtrochanteric and diaphyseal femoral fractures†
Very rare: Osteonecrosis of jaw†**, Osteonecrosis of the external auditory canal (bisphosphonat e class adverse reaction)†
Uncommon: Urinary retention, renal cyst
Uncommon: Pelvic pain
Common: Pyrexia, influenza-like illness**, oedema peripheral, asthenia, thirst
Uncommon: Hypothermia
Common: Gamma-GT increased, creatinine increased
Uncommon: Blood alkaline phosphatase increase, weight decrease
Uncommon: Injury, injection
** See further information below
† Identified in post-marketing experience
Decreased renal calcium excretion may be accompanied by a fall in serum phosphate levels not requiring therapeutic measures. The serum calcium level may fall to hypocalcaemic values.
A flu-like syndrome consisting of fever, chills, bone and/or muscle ache-like pain has occurred. In most cases no specific treatment was required and the symptoms subsided after a couple of hours/days.
Cases of osteonecrosis of the jaw have been reported, predominantly in cancer patients treated with medicinal products that inhibit bone resorption, such as ibandronic acid. Cases of ONJ have been reported in the post marketing setting for ibandronic acid.
Ocular inflammation events such as uveitis, episcleritis and scleritis have been reported with ibandronic acid. In some cases, these events did not resolve until the ibandronic acid was discontinued.
Cases of anaphylactic reaction/shock, including fatal events, have been reported in patients treated with intravenous ibandronic acid.
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