Iasibon

1 
 

  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Iasibon 1 mg concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One ampoule with 1 ml concentrate for solution for infusion contains 1 mg ibandronic acid (as sodium 
monohydrate). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate for solution for infusion.  
Clear, colourless solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Iasibon is indicated in adults for 
 
- Prevention of skeletal events (pathological fractures, bone complications requiring radiotherapy 

or surgery) in patients with breast cancer and bone metastases 
 

- Treatment of tumour-induced hypercalcaemia with or without metastases 
 
4.2 Posology and method of administration 
 
Iasibon therapy should only be initiated by physicians experienced in the treatment of cancer.  
 
Posology 
Prevention of skeletal events in patients with breast cancer and bone metastases 
 
The recommended dose for prevention of skeletal events in patients with breast cancer and bone 
metastases is 6 mg intravenous injection given every 3-4 weeks. The dose should be infused over at 
least 15 minutes.  
A shorter (i.e. 15 min) infusion time should only be used for patients with normal renal function or mild 
renal impairment. There are no data available characterising the use of a shorter infusion time in 
patients with creatinine clearance below 50 ml/min. Prescribers should consult the section Patients with 
Renal Impairment (see section 4.2) for recommendations on dosing and administration in this patient 
group. 
 
Treatment of tumour-induced hypercalcaemia 
 
Prior to treatment with Iasibon the patient should be adequately rehydrated with 9 mg/ml (0.9%) sodium 
chloride solution. Consideration should be given to the severity of the hypercalcaemia as well as the 
tumour type. In general patients with osteolytic bone metastases require lower doses than patients with 
the humoral type of hypercalcaemia. In most patients with severe hypercalcaemia (albumin-corrected 
serum calcium* ≥3 mmol/l or ≥12 mg/dl) 4 mg is an adequate single dose. In patients with moderate 
hypercalcaemia (albumin-corrected serum calcium <3 mmol/l or <12 mg/dl) 2 mg is an effective dose. 
The highest dose used in clinical trials was 6 mg but this dose does not add any further benefit in terms 
of efficacy. 
 



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* Note albumin-corrected serum calcium concentrations are calculated as follows: 
 
 Albumin-corrected serum calcium (mmol/l) = serum calcium (mmol/l) - [0.02 x albumin (g/l)] + 0.8 

or 
Albumin-corrected serum calcium (mg/dl) =serum calcium (mg/dl) + 0.8 x [4 - albumin (g/dl)] 
 
To convert the albumin-corrected serum calcium in mmol/l value to mg/dl, multiply by 4. 
 
In most cases a raised serum calcium level can be reduced to the normal range within 7 days. The 
median time to relapse (return of albumin-corrected serum calcium to levels above 3 mmol/l) was 18 - 
19 days for the 2 mg and 4 mg doses. The median time to relapse was 26 days with a dose of 6 mg. 
 
A limited number of patients (50 patients) have received a second infusion for hypercalcaemia. 
Repeated treatment may be considered in case of recurrent hypercalcaemia or insufficient efficacy. 
 
Iasibon concentrate for solution for infusion should be administered as an intravenous infusion over 2 
hours. 
 
Special populations 
Patients with hepatic impairment 
No dose adjustment is required (see section 5.2). 
 
Patients with renal impairment 
For patients with mild renal impairment (CLcr ≥50 and <80 mL/min) no dose adjustment is necessary. 
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 Volume 

1 and Time 2 

≥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. 
 
Elderly population (> 65 years) 
No dose adjustment is required (see section 5.2). 
 
Paediatric population 
The safety and efficacy of Iasibon in children and adolescents below the age of 18 years have not been 
established. No data are available (see section 5.1 and section 5.2). 
 
Method of administration 
For intravenous administration. 
 
The content of the ampoule is to be used as follows: 
 

• Prevention of Skeletal Events - added to 100 ml isotonic sodium chloride solution or 100 ml 5% 
dextrose solution and infused over at least 15 minutes. See also dose section above for patients 
with renal impairment 



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• Treatment of tumour-induced hypercalcaemia - added to 500 ml isotonic sodium chloride 

solution or 500 ml 5% dextrose solution and infused over 2 hours 
 
For single use only. Only clear solution without particles should be used. 
Iasibon concentrate for solution for infusion should be administered as an intravenous infusion.  
Care must be taken not to administer Iasibon concentrate for solution for infusion via intra-arterial or 
paravenous administration, as this could lead to tissue damage.. 
 
4.3 Contraindications 
 
− Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 
− Hypocalcaemia  
 
4.4 Special warnings and precautions for use 
 
Patients with disturbances of bone and mineral metabolism  
Hypocalcaemia and other disturbances of bone and mineral metabolism should be effectively treated 
before starting Iasibon therapy for metastatic bone disease.  
 
Adequate intake of calcium and vitamin D is important in all patients. Patients should receive 
supplemental calcium and/or vitamin D if dietary intake is inadequate. 
 
Anaphylactic reaction/shock 
Cases of anaphylactic reaction/shock, including fatal events, have been reported in patients treated with 
intravenous ibandronic acid. 
Appropriate medical support and monitoring measures should be readily available when Iasibon 
intravenous injection is administered. If anaphylactic or other severe hypersensitivity/allergic reactions 
occur, immediately discontinue the injection and initiate appropriate treatment. 
 
Osteonecrosis of the jaw  
Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including 
osteomyelitis) has been reported in patients with cancer receiving treatment regimens including 
primarily intravenously administered bisphosphonates. Many of these patients were also receiving 
chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in patients with 
osteoporosis receiving oral bisphosphonates.  
 
A dental examination with appropriate preventive dentistry should be considered prior to treatment with 
bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, radiotherapy, 
corticosteroids, poor oral hygiene).  
 
While on treatment, these patients should avoid invasive dental procedures if possible. For patients who 
develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the 
condition. For patients requiring dental procedures, there are no data available to suggest whether 
discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. Clinical 
judgement of the treating physician should guide the management plan of each patient based on 
individual benefit/risk assessment. 
 
Osteonecrosis of the external auditory canal 
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. 
 
Atypical fractures of the femur 



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Atypical subtrochanteric and diaphyseal femoral fractures have been reported with bisphosphonate 
therapy, primarily in patients receiving long-term treatment for osteoporosis. These transverse or short 
oblique fractures can occur anywhere along the femur from just below the lesser trochanter to just above 
the supracondylar flare. These fractures occur after minimal or no trauma and some patients experience 
thigh or groin pain, often associated with imaging features of stress fractures, weeks to months before 
presenting with a completed femoral fracture. Fractures are often bilateral; therefore the contralateral 
femur should be examined in bisphosphonate-treated patients who have sustained a femoral shaft 
fracture. Poor healing of these fractures has also been reported. Discontinuation of bisphosphonate 
therapy in patients suspected to have an atypical femur fracture should be considered pending 
evaluation of the patient, based on an individual benefit risk assessment. 
During bisphosphonate treatment patients should be advised to report any thigh, hip or groin pain and 
any patient presenting with such symptoms should be evaluated for an incomplete femur fracture. 
 
Patients with renal impairment  
Clinical studies have not shown any evidence of deterioration in renal function with long term Iasibon 
therapy. Nevertheless, according to clinical assessment of the individual patient, it is recommended that 
renal function, serum calcium, phosphate and magnesium should be monitored in patients treated with 
Iasibon (see section 4.2). 
 
Patients with hepatic impairment  
As no clinical data are available, dose recommendations cannot be given for patients with severe hepatic 
insufficiency (see section 4.2). 
 
Patients with cardiac impairment  
Overhydration should be avoided in patients at risk of cardiac failure. 
 
Patients with known hypersensitivity to other bisphosphonates 
Caution is to be taken in patients with known hypersensitivity to other bisphosphonates. 
 
Excipients with known effect 
 
Iasibon contains less than 1 mmol sodium (23 mg) per ampoule, i.e. essentially sodium free. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Metabolic interactions are not considered likely, since ibandronic acid does not inhibit the major human 
hepatic P450 isoenzymes and has been shown not to induce the hepatic cytochrome P450 system in rats 
(see section 5.2). Ibandronic acid is eliminated by renal excretion only and does not undergo any 
biotransformation. 
 
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. 
 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
There are no adequate data from the use of ibandronic acid in pregnant women. Studies in rats have 
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Therefore, 
Iasibon should not be used during pregnancy. 
 
Breast –feeding 
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. Iasibon should not be used during breast feeding. 
 



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Fertility 
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 (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
On the basis of the pharmacodynamic and pharmacokinetic profile and reported adverse reactions, it is 
expected that Iasibon has no or negligible influence on the ability to drive and use machines 
 
4.8 Undesirable effects 
 
 
Summary of the safety profile 
The most serious reported adverse reactions are anaphylactic reaction/shock, atypical fractures of the 
femur, osteonecrosis for the jaw, and ocular inflammation (see paragraph “description of selected 
adverse reactions” and section 4.4). 
 
Treatment of tumour induced hypercalcaemia is most frequently associated with a rise in body 
temperature. Less frequently, decrease in serum calcium below normal range (hypocalcaemia) is 
reported. In most cases no specific treatment is required and the symptoms subside 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. 
 
Tabulated list of adverse reactions 
Table 1 lists 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. 
 
Table 1 Adverse Reactions Reported for Intravenous Administration of Ibandronic Acid 
 
 
System Organ 
Class 

Very 
common 

Common Uncommon Rare Very rare Not known 

Infections and 
infestations 

 Infection Cystitis, vaginitis, 
oral candidiasis 

   

Neoplasms 
benign, 
malignant, 
and 
unspecified 

  Benign skin 
neoplasm 

   

Blood and 
lymphatic 
system 
disorders 

  Anaemia, blood 
dyscrasia 

   

Immune 
system 
disorders 

    Hypersensitivity
†, 
bronchospasm†, 
angioedema† 

Asthma 
exacerbation 



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System Organ 
Class 

Very 
common 

Common Uncommon Rare Very rare Not known 

anaphylactic 
reaction/shock†
** 

Endocrine 
disorders 

 Parathyroid 
disorder 

    

Metabolism 
and nutrition 
disorders 

 Hypocalcae
mia** 

Hypophosphatae
mia 

   

Psychiatric 
disorders 

  Sleep disorder, 
anxiety, affection 
lability 

   

Nervous 
system 
disorders 

 Headache, 
dizziness, 
dysgeusia 
(taste 
perversion) 

Cerebrovascular 
disorder, nerve 
root lesion , 
amnesia, 
migraine, 
neuralgia, 
hypertonia, 
hyperaestesia, 
paraesthesia 
circumoral, 
parosmia 

   

Eye disorders  Cataract  Ocular 
inflammati
on†** 

  

Ear and 
labyrinth 
disorders 

  Deafness    

Cardiac 
disorders 

 Bundle 
branch 
block 

Myocardial 
ischaemia, 
cardiovascular 
disorder, 
palpitations 

   

Respiratory, 
thoracic, and 
mediastinal 
disorders 

 Pharyngitis Lung oedema, 
stridor 

   

Gastrointestin
al disorders 

 Diarrhoea, 
vomiting, 
dyspepsia, 
gastrointest
inal pain, 
tooth 
disorder 

Gastroenteritis, 
gastritis, mouth 
ulceration, 
dysphagia, 
cheilitis 

   

Hepatobiliary 
disorders 

  Cholelithiasis    

Skin and 
subcutaneous 
tissue 
disorders 

 Skin 
disorder, 
ecchymosis 

Rash, alopecia  Stevens-Johnson 
Syndrome†, 
Erythema 
Multiforme†, 
Dermatitis 
Bullous† 

 



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System Organ 
Class 

Very 
common 

Common Uncommon Rare Very rare Not known 

Musculoskelet
al and 
connective 
tissue 
disorders 

 Osteoarthrit
is, myalgia, 
arthralgia, 
joint 
disorder, 
bone pain 

 Atypical 
subtrochant
eric and 
diaphyseal 
femoral 
fractures†  

Osteonecrosis of 
jaw†**, 
osteonecrosis of 
the external 
auditory canal 
(bisphosphonate 
class adverse 
reaction) 

 

Renal and 
urinary 
disorders 

  Urinary retention, 
renal cyst 

   

Reproductive 
system and 
breast 
disorders 

  Pelvic pain    

General 
disorders and 
administration 
site conditions 

 Pyrexia, 
influenza-
like 
illness**, 
oedema 
peripheral, 
asthenia, 
thirst 

Hypothermia    

Investigations  Gamma-
GT 
increased, 
creatinine 
increased 

Blood alkaline 
phosphatase 
increase, weight 
decrease 

   

Injury, 
poisoning and 
procedural 
complications 

  Injury, injection 
site pain 

   

**See further information below 
†Identified in postmarketing experience. 
 
Description of selected adverse reactions 
 
Hypocalcaemia 
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. 
 
Influenza-like illness 
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. 
 
Osteonecrosis of jaw 
Osteonecrosis of the jaw has been reported in patients treated by bisphosphonates. The majority of the 
reports refer to cancer patients, but such cases have also been reported in patients treated for 
osteoporosis. Osteonecrosis of the jaw is generally associated with tooth extraction and/or local 
infection (including osteomyelitis). Diagnosis of cancer, chemotherapy, radiotherapy, corticosteroids 
and poor oral hygiene are also deemed as risk factors (see section 4.4). 
 
Ocular inflammation 
Ocular inflammation events such as uveitis, episcleritis and scleritis have been reported with  



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ibandronic acid. In some cases, these events did not resolve until the ibandronic acid was discontinued. 
 
Anaphylactic reaction/shock 
Cases of anaphylactic reaction/shock, including fatal events, have been reported in patients treated with 
intravenous ibandronic acid. 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system listed 
in Appendix V. 
 
4.9 Overdose 
 
Up to now there is no experience of acute poisoning with Iasibon concentrate for solution for infusion. 
Since both the kidney and the liver were found to be target organs for toxicity in preclinical studies with 
high doses, kidney and liver function should be monitored. Clinically relevant hypocalcaemia should be 
corrected by intravenous administration of calcium gluconate. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmaco-therapeutic group: Medicinal products for treatment of bone diseases, bisphosphonate, ATC 
Code: M05BA06 
 
Ibandronic acid belongs to the bisphosphonate group of compounds which act specifically on bone. 
Their selective action on bone tissue is based on the high affinity of bisphosphonates for bone mineral. 
Bisphosphonates act by inhibiting osteoclast activity, although the precise mechanism is still not clear. 
 
In vivo, ibandronic acid prevents experimentally-induced bone destruction caused by cessation of 
gonadal function, retinoids, tumours or tumour extracts. The inhibition of endogenous bone resorption 
has also been documented by 45Ca kinetic studies and by the release of radioactive tetracycline 
previously incorporated into the skeleton. 
 
At doses that were considerably higher than the pharmacologically effective doses, ibandronic acid did 
not have any effect on bone mineralisation. 
 
Bone resorption due to malignant disease is characterised by excessive bone resorption that is not 
balanced with appropriate bone formation. Ibandronic acid selectively inhibits osteoclast activity, 
reducing bone resorption and thereby reducing skeletal complications of the malignant disease. 
 
Clinical studies in the treatment of tumour-induced hypercalcaemia 
Clinical studies in hypercalcaemia of malignancy demonstrated that the inhibitory effect of ibandronic 
acid on tumour-induced osteolysis, and specifically on tumour-induced hypercalcaemia, is characterised 
by a decrease in serum calcium and urinary calcium excretion. 
 
In the dose range recommended for treatment, the following response rates with the respective 
confidence intervals have been shown in clinical trials for patients with baseline albumin-corrected 
serum calcium ≥ 3.0 mmol/l after adequate rehydration. 
 
Ibandronic 
acid dose 

% of Patients with 
Response 

90% Confidence 
Interval 

2 mg 54 44-63 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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4 mg 76 62-86 

6 mg 78 64-88 

 
 
For these patients and dosages, the median time to achieve normocalcaemia was 4 to 7 days. The 
median time to relapse (return of albumin-corrected serum calcium above 3.0 mmol/l) was 18 to 26 
days. 
 
Clinical studies in the prevention of skeletal events in patients with breast cancer and bone metastases 
Clinical studies in patients with breast cancer and bone metastases have shown that there is a dose 
dependent inhibitory effect on bone osteolysis, expressed by markers of bone resorption, and a dose 
dependent effect on skeletal events. 
 
Prevention of skeletal events in patients with breast cancer and bone metastases with Ibandronate6 mg 
administered intravenously was assessed in one randomized placebo controlled phase III trial with 
duration of 96 weeks. Female patients with breast cancer and radiologically confirmed bone metastases 
were randomised to receive placebo (158 patients) or 6 mg Ibandronate (154 patients). The results from 
this trial are summarised below. 
 
Primary efficacy endpoints 
The primary endpoint of the trial was the skeletal morbidity period rate (SMPR). This was a composite 
endpoint which had the following skeletal related events (SREs) as sub-components: 

 
- radiotherapy to bone for treatment of fractures/impending fractures 
- surgery to bone for treatment of fractures 
- vertebral fractures 
- non-vertebral fractures 
 
The analysis of the SMPR was time-adjusted and considered that one or more events occurring in a 
single 12 week period could be potentially related. Multiple events were therefore counted only once for 
the purposes of the analysis. Data from this study demonstrated a significant advantage for intravenous 
Ibandronate 6 mg over placebo in the reduction in SREs measured by the time-adjusted SMPR 
(p=0.004). The number of SREs was also significantly reduced with Ibandronate 6 mg and there was a 
40% reduction in the risk of a SRE over placebo (relative risk 0.6, p = 0.003). Efficacy results are 
summarised in table 2. 
 
Table 2 Efficacy Results (Breast Cancer Patients with Metastatic Bone Disease) 
 
 All Skeletal Related Events (SREs) 

Placebo 
n=158 

Ibandronate 6 mg 
n=154 

p-value 

SMPR (per patient year) 1.48 1.19 p=0.004 

Number of events (per 
patient) 

3.64 2.65 p=0.025 

SRE relative risk - 0.60 p=0.003 

 
Secondary efficacy endpoints 
A statistically significant improvement in bone pain score was shown for intravenous Ibandronate 6 mg 
compared to placebo. The pain reduction was consistently below baseline throughout the entire study 
and accompanied by a significantly reduced use of analgesics. The deterioration in Quality of Life was 
significantly less in Ibandronate treated patients compared with placebo. A tabular summary of these 



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secondary efficacy results is presented in Table 3. 
 
Table 3 Secondary efficacy results (breast cancer patients with metastatic bone disease) 
 
 Placebo 

n=158 
Ibandronate 6 mg 
n=154 

p-value 

Bone pain * 0.21 -0.28 p<0.001 

Analgesic use * 0.90 0.51 p=0.083 

Quality of Life * -45.4 -10.3 p=0.004 

* Mean change from baseline to last assessment. 
 
There was a marked depression of urinary markers of bone resorption (pyridinoline and 
deoxypyridinoline) in patients treated with Ibandronate that was statistically significant compared to 
placebo. 
 
In a study in 130 patients with metastatic breast cancer the safety of Ibandronate infused over 1 hour or 
15 minutes was compared. No difference was observed in the indicators of renal function. The overall 
adverse event profile of ibandronic acid following the 15 minute infusion was consistent with the 
known safety profile over longer infusion times and no new safety concerns were identified relating to 
the use of a 15  minute infusion time. 
 
A 15 minute infusion time has not been studied in cancer patients with a creatinine clearance of 
<50 ml/min. 
 
Paediatric population (see section 4.2 and section 5.2) 
The safety and efficacy of Iasibon in children and adolescents below the age of 18 years have not been 
established. No data are available. 
 
5.2 Pharmacokinetic properties 
 
After a 2 hour infusion of 2, 4 and 6 mg ibandronic acid pharmacokinetic parameters are dose 
proportional. 
 
Distribution 
After initial systemic exposure, ibandronic acid rapidly binds to bone or is excreted into urine. In 
humans, the apparent terminal volume of distribution is at least 90 l and the amount of dose reaching the 
bone is estimated to be 40-50% of the circulating dose. Protein binding in human plasma is 
approximately 87% at therapeutic concentrations, and thus interaction with other medicinal products, 
due to displacement is unlikely. 
 
Biotransformation 
There is no evidence that ibandronic acid is metabolized in animals or humans. 
 
Elimination 
The range of observed apparent half-lives is broad and dependent on dose and assay sensitivity, but the 
apparent terminal half-life is generally in the range of 10-60 hours. However, early plasma levels fall 
quickly, reaching 10% of peak values within 3 and 8 hours after intravenous or oral administration 
respectively. No systemic accumulation was observed when ibandronic acid was administered 
intravenously once every 4 weeks for 48 weeks to patients with metastatic bone disease. 
 
Total clearance of ibandronic acid is low with average values in the range 84-160 ml/min. Renal 
clearance (about 60 ml/min in healthy postmenopausal females) accounts for 50-60% of total clearance 



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and is related to creatinine clearance. The difference between the apparent total and renal clearances is 
considered to reflect the uptake by bone. 
 
The secretory pathway of renal elimination does not appear to include known acidic or basic transport 
systems involved in the excretion of other active substances. In addition, ibandronic acid does not 
inhibit the major human hepatic P450 isoenzymes and does not induce the hepatic cytochrome P450 
system in rats. 
 
Pharmacokinetics in special populations 
 
Gender 
Bioavailability and pharmacokinetics of ibandronic acid are similar in both men and women. 
 
Race 
There is no evidence for clinically relevant interethnic differences between Asians and Caucasians in 
ibandronic acid disposition. There are only very few data available on patients with African origin. 
 
Patients with renal impairment 
Exposure to ibandronic acid in patients with various degrees of renal impairment is related to creatinine 
clearance (CLcr). In subjects with severe renal impairment (mean estimated CLcr = 21.2 mL/min), 
dose-adjusted mean AUC0-24h was increased by 110% compared to healthy volunteers. In clinical 
pharmacology trial WP18551, after a single dose intravenous administration of 6 mg (15 minutes 
infusion), mean AUC0-24 increased by 14% and 86%, respectively, in subjects with mild (mean 
estimated CLcr=68.1 mL/min) and moderate (mean estimated CLcr=41.2 mL/min) renal impairment 
compared to healthy volunteers (mean estimated CLcr=120 mL/min). Mean Cmax was not increased in 
patients with mild renal impairment and increased by 12% in patients with moderate renal impairment. 
For patients with mild renal impairment (CLcr ≥50 and <80 mL/min) no dosage adjustment is 
necessary. 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 an adjustment in the dose is recommended (see section 4.2). 
 
Patients with hepatic impairment (see section 4.2) 
There are no pharmacokinetic data for ibandronic acid in patients who have hepatic impairment. The 
liver has no significant role in the clearance of ibandronic acid since it is not metabolized but is 
cleared by renal excretion and by uptake into bone. Therefore dosage adjustment is not necessary in 
patients with hepatic impairment. Further, as protein binding of ibandronic acid is approximately 87% at 
therapeutic concentrations, hypoproteinaemia in severe liver disease is unlikely to lead to clinically 
significant increases in free plasma concentration. 
 
Elderly (see section 4.2) 
In a multivariate analysis, age was not found to be an independent factor of any of the pharmacokinetic 
parameters studied. As renal function decreases with age, this is the only factor that should be 
considered (see renal impairment section). 
 
Paediatric population (see section 4.2 and section 5.1) 
There are no data on the use of Iasibon in patients less than 18 years old. 
 
5.3 Preclinical safety data 
Effects in non-clinical studies were observed only at exposures sufficiently in excess of the maximum 
human exposure indicating little relevance to clinical use. As with other bisphosphonates, the kidney 
was identified to be the primary target organ of systemic toxicity. 
 
Mutagenicity/Carcinogenicity: 
No indication of carcinogenic potential was observed. Tests for genotoxicity revealed no evidence of 
effects on genetic activity for ibandronic acid. 
 
Reproductive toxicity: 



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No evidence of direct foetal toxicity or teratogenic effects were observed for ibandronic acid in 
intravenously treated rats and rabbits. In reproductive studies in rats by the oral route, effects on fertility 
consisted of increased preimplantation losses at dose levels of 1 mg/kg/day and higher. In reproductive 
studies in rats by the intravenous route, ibandronic acid decreased sperm counts at doses of 0.3 and 1 
mg/kg/day and decreased fertility in males at 1 mg/kg/day and in females at 1.2 mg/kg/day. Adverse 
effects of ibandronic acid in reproductive toxicity studies in the rat were those expected for this class of 
medicinal products (bisphosphonates). They include a decreased number of implantation sites, 
interference with natural delivery (dystocia), an increase in visceral variations (renal pelvis ureter 
syndrome) and teeth abnormalities in F1 offspring in rats. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium chloride 
Acetic acid, glacial  
Sodium acetate trihydrate 
Water for injections 
 
6.2 Incompatibilities 
 
To avoid potential incompatibilities Iasibon concentrate for solution for infusion should only be diluted 
with isotonic sodium chloride solution or 5% glucose solution. 
 
Iasibon should not be mixed with calcium containing solutions. 
 
6.3 Shelf life 
 
5 years.  
After reconstitution: 24 hours. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions prior to reconstitution. 
  
 
After reconstitution: Store at 2°C - 8°C (in a refrigerator). 
 
From a microbiological point of view, the product should be used immediately. If not used immediately, 
in-use storage times and conditions prior to use are the responsibility of the user and would normally 
not be longer than 24 hours at 2 to 8 °C, unless reconstitution has taken place in controlled and 
validated aseptic conditions. 
 
6.5 Nature and contents of container 
 
Iasibon 1 mg is supplied as pack containing 1 ampoule (2 ml type I glass ampoule). 
 
6.6 Special precautions for disposal  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
The release of pharmaceuticals in the environment should be minimized. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 



   14 
 

Pharmathen S.A. 
Dervenakion 6 
Pallini Attiki, 15351 
Greece 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/10/659/003 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 21 January 2011 
Date of latest renewal: 30 September 2015 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu/. 
 

http://www.ema.europa.eu/


   15 
 

1. NAME OF THE MEDICINAL PRODUCT 
 
Iasibon 2 mg concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One ampoule with 2 ml concentrate for solution for infusion contains 2 mg ibandronic acid (as sodium 
monohydrate). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate for solution for infusion.  
Clear, colourless solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Iasibon is indicated in adults for 
 
- Prevention of skeletal events (pathological fractures, bone complications requiring radiotherapy 

or surgery) in patients with breast cancer and bone metastases 
 

- Treatment of tumour-induced hypercalcaemia with or without metastases 
 
4.2 Posology and method of administration 
 
Iasibon therapy should only be initiated by physicians experienced in the treatment of cancer.  
 
Posology 
Prevention of skeletal events in patients with breast cancer and bone metastases 
 
The recommended dose for prevention of skeletal events in patients with breast cancer and bone 
metastases is 6 mg intravenous injection given every 3-4 weeks. The dose should be infused over at 
least 15 minutes.  
A shorter (i.e. 15 min) infusion time should only be used for patients with normal renal function or mild 
renal impairment. There are no data available characterising the use of a shorter infusion time in 
patients with creatinine clearance below 50 ml/min. Prescribers should consult the section Patients with 
Renal Impairment (see section 4.2) for recommendations on dosing and administration in this patient 
group. 
 
Treatment of tumour-induced hypercalcaemia 
 
Prior to treatment with Iasibon the patient should be adequately rehydrated with 9 mg/ml (0.9%) sodium 
chloride solution. Consideration should be given to the severity of the hypercalcaemia as well as the 
tumour type. In general patients with osteolytic bone metastases require lower doses than patients with 
the humoral type of hypercalcaemia. In most patients with severe hypercalcaemia (albumin-corrected 
serum calcium* ≥3 mmol/l or ≥12 mg/dl) 4 mg is an adequate single dose. In patients with moderate 
hypercalcaemia (albumin-corrected serum calcium <3 mmol/l or <12 mg/dl) 2 mg is an effective dose. 
The highest dose used in clinical trials was 6 mg but this dose does not add any further benefit in terms 
of efficacy. 
 



   16 
 

* Note albumin-corrected serum calcium concentrations are calculated as follows: 
 
 Albumin-corrected serum calcium (mmol/l) = serum calcium (mmol/l) - [0.02 x albumin (g/l)] + 0.8 

or 
Albumin-corrected serum calcium (mg/dl) =serum calcium (mg/dl) + 0.8 x [4 - albumin (g/dl)] 
 
To convert the albumin-corrected serum calcium in mmol/l value to mg/dl, multiply by 4. 
 
In most cases a raised serum calcium level can be reduced to the normal range within 7 days. The 
median time to relapse (return of albumin-corrected serum calcium to levels above 3 mmol/l) was 18 - 
19 days for the 2 mg and 4 mg doses. The median time to relapse was 26 days with a dose of 6 mg. 
 
A limited number of patients (50 patients) have received a second infusion for hypercalcaemia. 
Repeated treatment may be considered in case of recurrent hypercalcaemia or insufficient efficacy. 
 
Iasibon concentrate for solution for infusion should be administered as an intravenous infusion over 2 
hours. 
 
Special populations  
Patients with hepatic impairment 
No dose adjustment is required (see section 5.2). 
 
Patients with renal impairment 
For patients with mild renal impairment (CLcr ≥50 and <80 mL/min) no dose adjustment is necessary. 
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 Volume 

1 and Time 2 

≥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. 
 
Elderly population (> 65 years) 
No dose adjustment is required (see section 5.2). 
 
Paediatric population 
The safety and efficacy of Iasibon in children and adolescents below the age of 18 years have not been 
established. No data are available. (see section 5.1 and section 5.2). 
 
Method of administration 
For intravenous administration. 
 
The content of the ampoule is to be used as follows: 
 
• Prevention of Skeletal Events - added to 100 ml isotonic sodium chloride solution or 100 ml 5% 
dextrose solution and infused over at least 15 minutes. See also dose section above for patients with 
renal impairment 



   17 
 

 
• Treatment of tumour-induced hypercalcaemia - added to 500 ml isotonic sodium chloride 
solution or 500 ml 5% dextrose solution and infused over 2 hours 
 
For single use only. Only clear solution without particles should be used. 
Iasibon concentrate for solution for infusion should be administered as an intravenous infusion. 
Care must be taken to ensure that administer Iasibon concentrate for solution for infusion via intra-
arterial or paravenous administration, as this could lead to tissue damage. 
 
4.3 Contraindications 
 
− Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 
− Hypocalcaemia  
 
4.4 Special warnings and precautions for use 
 
Patients with disturbances of bone and mineral metabolism  
Hypocalcaemia and other disturbances of bone and mineral metabolism should be effectively treated 
before starting Iasibon therapy for metastatic bone disease.  
 
Adequate intake of calcium and vitamin D is important in all patients. Patients should receive 
supplemental calcium and/or vitamin D if dietary intake is inadequate. 
 
Anaphylactic reaction/shock 
Cases of anaphylactic reaction/shock, including fatal events, have been reported in patients treated with 
intravenous ibandronic acid. 
Appropriate medical support and monitoring measures should be readily available when Iasibon 
intravenous injection is administered. If anaphylactic or other severe hypersensitivity/allergic reactions 
occur, immediately discontinue the injection and initiate appropriate treatment. 
 
Osteonecrosis of the jaw  
Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including 
osteomyelitis) has been reported in patients with cancer receiving treatment regimens including 
primarily intravenously administered bisphosphonates. Many of these patients were also receiving 
chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in patients with 
osteoporosis receiving oral bisphosphonates.  
 
A dental examination with appropriate preventive dentistry should be considered prior to treatment with 
bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, radiotherapy, 
corticosteroids, poor oral hygiene).  
 
While on treatment, these patients should avoid invasive dental procedures if possible. For patients who 
develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the 
condition. For patients requiring dental procedures, there are no data available to suggest whether 
discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. Clinical 
judgement of the treating physician should guide the management plan of each patient based on 
individual benefit/risk assessment. 
 
Osteonecrosis of the external auditory canal 
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. 
 
Atypical fractures of the femur 



   18 
 

Atypical subtrochanteric and diaphyseal femoral fractures have been reported with bisphosphonate 
therapy, primarily in patients receiving long-term treatment for osteoporosis. These transverse or short 
oblique fractures can occur anywhere along the femur from just below the lesser trochanter to just above 
the supracondylar flare. These fractures occur after minimal or no trauma and some patients experience 
thigh or groin pain, often associated with imaging features of stress fractures, weeks to months before 
presenting with a completed femoral fracture. Fractures are often bilateral; therefore the contralateral 
femur should be examined in bisphosphonate-treated patients who have sustained a femoral shaft 
fracture. Poor healing of these fractures has also been reported. Discontinuation of bisphosphonate 
therapy in patients suspected to have an atypical femur fracture should be considered pending 
evaluation of the patient, based on an individual benefit risk assessment. 
During bisphosphonate treatment patients should be advised to report any thigh, hip or groin pain and 
any patient presenting with such symptoms should be evaluated for an incomplete femur fracture. 
 
Patients with renal impairment  
Clinical studies have not shown any evidence of deterioration in renal function with long term Iasibon 
therapy. Nevertheless, according to clinical assessment of the individual patient, it is recommended that 
renal function, serum calcium, phosphate and magnesium should be monitored in patients treated with 
Iasibon . (see section 4.2). 
 
Patients with hepatic impairment  
As no clinical data are available, dosage recommendations cannot be given for patients with severe 
hepatic insufficiency (see section 4.2).. 
 
Patients with cardiac impairment  
Overhydration should be avoided in patients at risk of cardiac failure. 
 
Patients with known hypersensitivity to other bisphosphonates 
Caution is to be taken in patients with known hypersensitivity to other bisphosphonates. 
 
Excipients with known effect  
 
Iasibon contains less than 1 mmol sodium (23 mg) per ampoule, i.e. essentially sodium free. 

 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Metabolic interactions are not considered likely, since ibandronic acid does not inhibit the major human 
hepatic P450 isoenzymes and has been shown not to induce the hepatic cytochrome P450 system in rats 
(see section 5.2). Ibandronic acid is eliminated by renal excretion only and does not undergo any 
biotransformation. 
 
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. 
 
 
4.6 Fertility, pregnancy and lactation 
 
Pegnancy 
There are no adequate data from the use of ibandronic acid in pregnant women. Studies in rats have 
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Therefore, 
Iasibon should not be used during pregnancy. 
 
Breast –feeding 
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. Iasibon should not be used during breat-feeding. 



   19 
 

 
Fertility 
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 (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
On the basis of the pharmacodynamic and pharmacokinetic profile and reported adverse reactions, it is 
expected that Iasibon has no or negligible influence on the ability to drive and use machines.  
 
4.8 Undesirable effects 
 
Summary of the safety profile 
The most serious reported adverse reactions are anaphylactic reaction/shock, atypical fractures of the 
femur, osteonecrosis for the jaw, and ocular inflammation (see paragraph “description of selected 
adverse reactions” and section 4.4). 
Treatment of tumour induced hypercalcaemia is most frequently associated with a rise in body 
temperature. Less frequently, decrease in serum calcium below normal range (hypocalcaemia) is 
reported.  
In most cases no specific treatment is required and the symptoms subside 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. 
 
Tabulated list of adverse reactions 
Table 1 lists 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. 
 
Table 1 Adverse Reactions  Reported for Intravenous Administration of Ibandronic Acid 
 
 
System Organ 
Class 

Very 
common 

Common Uncommon Rare Very rare Not known 

Infections and 
infestations 

 Infection Cystitis, vaginitis, 
oral candidiasis 

   

Neoplasms 
benign, 
malignant, 
and 
unspecified 

  Benign skin 
neoplasm 

   

Blood and 
lymphatic 
system 
disorders 

  Anaemia, blood 
dyscrasia 

   

Immune 
system 
disorders 

    Hypersensitivity†, 
bronchospasm†, 
angioedema† 
anaphylactic 
reaction/shock†** 

Asthma 
exacerbation 



   20 
 

 
System Organ 
Class 

Very 
common 

Common Uncommon Rare Very rare Not known 

Endocrine 
disorders 

 Parathyroid 
disorder 

    

Metabolism 
and nutrition 
disorders 

 Hypocalcae
mia** 

Hypophosphatae
mia 

   

Psychiatric 
disorders 

  Sleep disorder, 
anxiety, affection 
lability 

   

Nervous 
system 
disorders 

 Headache, 
dizziness, 
dysgeusia 
(taste 
perversion) 

Cerebrovascular 
disorder, nerve 
root lesion , 
amnesia, 
migraine, 
neuralgia, 
hypertonia, 
hyperaestesia, 
paraesthesia 
circumoral, 
parosmia 

   

Eye disorders  Cataract  Ocular 
inflammat
ion†** 

  

Ear and 
labyrinth 
disorders 

  Deafness    

Cardiac 
disorders 

 Bundle 
branch block 

Myocardial 
ischaemia, 
cardiovascular 
disorder, 
palpitations 

   

Respiratory, 
thoracic, and 
mediastinal 
disorders 

 Pharyngitis Lung oedema, 
stridor 

   

Gastrointestin
al disorders 

 Diarrhoea, 
vomiting, 
dyspepsia, 
gastrointestin
al pain, tooth 
disorder 

Gastroenteritis, 
gastritis, mouth 
ulceration, 
dysphagia, 
cheilitis 

   

Hepatobiliary 
disorders 

  Cholelithiasis    

Skin and 
subcutaneous 
tissue 
disorders 

 Skin 
disorder, 
ecchymosis 

Rash, alopecia  Stevens-Johnson 
Syndrome†, 
Erythema 
Multiforme†, 
Dermatitis 
Bullous† 

 

Musculoskelet
al and 
connective 
tissue 
disorders 

 Osteoarthritis
, myalgia, 
arthralgia, 
joint 
disorder, 
bone pain 

 Atypical 
subtrocha
nteric and 
diaphysea
l femoral 
fractures†  

Osteonecrosis of 
jaw†**, 
osteonecrosis of 
the external 
auditory canal 
(bisphosphonate 

 



   21 
 

 
System Organ 
Class 

Very 
common 

Common Uncommon Rare Very rare Not known 

class adverse 
reaction) 

Renal and 
urinary 
disorders 

  Urinary retention, 
renal cyst 

   

Reproductive 
system and 
breast 
disorders 

  Pelvic pain    

General 
disorders and 
administration 
site conditions 

 Pyrexia, 
influenza-
like 
illness**, 
oedema 
peripheral, 
asthenia, 
thirst 

Hypothermia    

Investigations  Gamma-GT 
increased, 
creatinine 
increased 

Blood alkaline 
phosphatase 
increase, weight 
decrease 

   

Injury, 
poisoning and 
procedural 
complications 

  Injury, injection 
site pain 

   

**See further information below 
†Identified in postmarketing experience. 
 
Description of selected adverse reactions 
 
Hypocalcaemia 
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. 
 
Influenza-like illness 
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. 
 
Osteonecrosis of jaw 
Osteonecrosis of the jaw has been reported in patients treated by bisphosphonates. The majority of the 
reports refer to cancer patients, but such cases have also been reported in patients treated for 
osteoporosis. Osteonecrosis of the jaw is generally associated with tooth extraction and/ or local 
infection (including osteomyelitis). Diagnosis of cancer, chemotherapy, radiotherapy, corticosteroids 
and poor oral hygiene are also deemed as risk factors (see section 4.4). 
 
Ocular inflammation 
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. 
 
Anaphylactic reaction/shock 



   22 
 

Cases of anaphylactic reaction/shock, including fatal events, have been reported in patients treated with 
intravenousibandronic acid. 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system listed 
in Appendix V. 
 
4.9 Overdose 
 
Up to now there is no experience of acute poisoning with Iasibon concentrate for solution for infusion. 
Since both the kidney and the liver were found to be target organs for toxicity in preclinical studies with 
high doses, kidney and liver function should be monitored. Clinically relevant hypocalcaemia should be 
corrected by intravenous administration of calcium gluconate. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmaco-therapeutic group: Medicinal products for treatment of bone diseases, bisphosphonate, ATC 
Code: M05BA06 
 
Ibandronic acid belongs to the bisphosphonate group of compounds which act specifically on bone. 
Their selective action on bone tissue is based on the high affinity of bisphosphonates for bone mineral. 
Bisphosphonates act by inhibiting osteoclast activity, although the precise mechanism is still not clear. 
 
In vivo, ibandronic acid prevents experimentally-induced bone destruction caused by cessation of 
gonadal function, retinoids, tumours or tumour extracts. The inhibition of endogenous bone resorption 
has also been documented by 45Ca kinetic studies and by the release of radioactive tetracycline 
previously incorporated into the skeleton. 
 
At doses that were considerably higher than the pharmacologically effective doses, ibandronic acid did 
not have any effect on bone mineralisation. 
 
Bone resorption due to malignant disease is characterised by excessive bone resorption that is not 
balanced with appropriate bone formation. Ibandronic acid selectively inhibits osteoclast activity, 
reducing bone resorption and thereby reducing skeletal complications of the malignant disease. 
 
Clinical studies in the treatment of tumour-induced hypercalcaemia 
Clinical studies in hypercalcaemia of malignancy demonstrated that the inhibitory effect of ibandronic 
acid on tumour-induced osteolysis, and specifically on tumour-induced hypercalcaemia, is characterised 
by a decrease in serum calcium and urinary calcium excretion. 
 
In the dose range recommended for treatment, the following response rates with the respective 
confidence intervals have been shown in clinical trials for patients with baseline albumin-corrected 
serum calcium ≥ 3.0 mmol/l after adequate rehydration. 
 
Ibandronic 
acid dose 

% of Patients with 
Response 

90% Confidence 
Interval 

2 mg 54 44-63 

4 mg 76 62-86 

6 mg 78 64-88 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


   23 
 

 
For these patients and dosages, the median time to achieve normocalcaemia was 4 to 7 days. The 
median time to relapse (return of albumin-corrected serum calcium above 3.0 mmol/l) was 18 to 26 
days. 
 
Clinical studies in the prevention of skeletal events in patients with breast cancer and bone metastases 
Clinical studies in patients with breast cancer and bone metastases have shown that there is a dose 
dependent inhibitory effect on bone osteolysis, expressed by markers of bone resorption, and a dose 
dependent effect on skeletal events. 
 
Prevention of skeletal events in patients with breast cancer and bone metastases with Ibandronate 6 mg 
administered intravenously was assessed in one randomized placebo controlled phase III trial with 
duration of 96 weeks. Female patients with breast cancer and radiologically confirmed bone metastases 
were randomised to receive placebo (158 patients) or 6 mg Ibandronate (154 patients). The results from 
this trial are summarised below. 
 
Primary efficacy endpoints 
The primary endpoint of the trial was the skeletal morbidity period rate (SMPR). This was a composite 
endpoint which had the following skeletal related events (SREs) as sub-components: 

 
- radiotherapy to bone for treatment of fractures/impending fractures 
- surgery to bone for treatment of fractures 
- vertebral fractures 
- non-vertebral fractures 
 
The analysis of the SMPR was time-adjusted and considered that one or more events occurring in a 
single 12 week period could be potentially related. Multiple events were therefore counted only once for 
the purposes of the analysis. Data from this study demonstrated a significant advantage for intravenous 
Ibandronate 6 mg over placebo in the reduction in SREs measured by the time-adjusted SMPR 
(p=0.004). The number of SREs was also significantly reduced with Ibandronate 6 mg and there was a 
40% reduction in the risk of a SRE over placebo (relative risk 0.6, p = 0.003). Efficacy results are 
summarised in table 2. 
 
Table 2 Efficacy Results (Breast Cancer Patients with Metastatic Bone Disease) 
 
 All Skeletal Related Events (SREs) 

Placebo 
n=158 

Ibandronate 6 mg 
n=154 

p-value 

SMPR (per patient year) 1.48 1.19 p=0.004 

Number of events (per 
patient) 

3.64 2.65 p=0.025 

SRE relative risk - 0.60 p=0.003 

 
Secondary efficacy endpoints 
A statistically significant improvement in bone pain score was shown for intravenous Ibandronate 6 mg 
compared to placebo. The pain reduction was consistently below baseline throughout the entire study 
and accompanied by a significantly reduced use of analgesics. The deterioration in Quality of Life was 
significantly less in Ibandronate treated patients compared with placebo. A tabular summary of these 
secondary efficacy results is presented in table 3. 
 
Table 3 Secondary efficacy results (breast cancer patients with metastatic bone disease) 
 



   24 
 

 Placebo 
n=158 

Ibandronate 6 mg 
n=154 

p-value 

Bone pain * 0.21 -0.28 p<0.001 

Analgesic use * 0.90 0.51 p=0.083 

Quality of Life * -45.4 -10.3 p=0.004 

* Mean change from baseline to last assessment. 
 
There was a marked depression of urinary markers of bone resorption (pyridinoline and 
deoxypyridinoline) in patients treated with Ibandronate that was statistically significant compared to 
placebo. 
 
In a study in 130 patients with metastatic breast cancer the safety of Ibandronate infused over 1 hour or 
15 minutes was compared. No difference was observed in the indicators of renal function. The overall 
adverse event profile of ibandronic acid following the 15 minute infusion was consistent with the 
known safety profile over longer infusion times and no new safety concerns were identified relating to 
the use of a 15  minute infusion time. 
 
A 15 minute infusion time has not been studied in cancer patients with a creatinine clearance of 
<50 ml/min. 
 
Paediatric population(see section 4.2 and section 5.2) 
The safety and efficacy of Iasibon in children and adolescents below the age of 18 years have not been 
established. No data are available. 
 
5.2 Pharmacokinetic properties 
 
After a 2 hour infusion of 2, 4 and 6 mg ibandronic acid pharmacokinetic parameters are dose 
proportional. 
 
Distribution 
After initial systemic exposure, ibandronic acid rapidly binds to bone or is excreted into urine. In 
humans, the apparent terminal volume of distribution is at least 90 l and the amount of dose reaching the 
bone is estimated to be 40-50% of the circulating dose. Protein binding in human plasma is 
approximately 87% at therapeutic concentrations, and thus interaction with other medicinal products, 
due to displacement is unlikely. 
 
Biotransformation 
There is no evidence that ibandronic acid is metabolized in animals or humans. 
 
Elimination 
The range of observed apparent half-lives is broad and dependent on dose and assay sensitivity, but the 
apparent terminal half-life is generally in the range of 10-60 hours. However, early plasma levels fall 
quickly, reaching 10% of peak values within 3 and 8 hours after intravenous or oral administration 
respectively. No systemic accumulation was observed when ibandronic acid was administered 
intravenously once every 4 weeks for 48 weeks to patients with metastatic bone disease. 
 
Total clearance of ibandronic acid is low with average values in the range 84-160 ml/min. Renal 
clearance (about 60 ml/min in healthy postmenopausal females) accounts for 50-60% of total clearance 
and is related to creatinine clearance. The difference between the apparent total and renal clearances is 
considered to reflect the uptake by bone. 
 
The secretory pathway of renal elimination does not appear to include known acidic or basic transport 



   25 
 

systems involved in the excretion of other active substances. In addition, ibandronic acid does not 
inhibit the major human hepatic P450 isoenzymes and does not induce the hepatic cytochrome P450 
system in rats. 
 
Pharmacokinetics in special populations 
 
Gender 
Bioavailability and pharmacokinetics of ibandronic acid are similar in both men and women. 
 
Race 
There is no evidence for clinically relevant interethnic differences between Asians and Caucasians in 
ibandronic acid disposition. There are only very few data available on patients with African origin. 
 
Patients with renal impairment 
Exposure to ibandronic acid in patients with various degrees of renal impairment is related to creatinine 
clearance (CLcr). In subjects with severe renal impairment (mean estimated CLcr = 21.2 mL/min), 
dose-adjusted mean AUC0-24h was increased by 110% compared to healthy volunteers. In clinical 
pharmacology trial WP18551, after a single dose intravenous administration of 6 mg (15 minutes 
infusion), mean AUC0-24 increased by 14% and 86%, respectively, in subjects with mild (mean 
estimated CLcr=68.1 mL/min) and moderate (mean estimated CLcr=41.2 mL/min) renal impairment 
compared to healthy volunteers (mean estimated CLcr=120 mL/min). Mean Cmax was not increased in 
patients with mild renal impairment and increased by 12% in patients with moderate renal impairment. 
For patients with mild renal impairment (CLcr ≥50 and <80 mL/min) no dosage adjustment is 
necessary. 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 an adjustment in the dose is recommended (see section 4.2). 
 
Patients with hepatic impairment (see section 4.2) 
There are no pharmacokinetic data for ibandronic acid in patients who have hepatic impairment. The 
liver has no significant role in the clearance of ibandronic acid since it is not metabolized but is 
cleared by renal excretion and by uptake into bone. Therefore dosage adjustment is not necessary in 
patients with hepatic impairment. Further, as protein binding of ibandronic acid is approximately 87% at 
therapeutic concentrations, hypoproteinaemia in severe liver disease is unlikely to lead to clinically 
significant increases in free plasma concentration. 
 
Elderly (see section 4.2) 
In a multivariate analysis, age was not found to be an independent factor of any of the pharmacokinetic 
parameters studied. As renal function decreases with age, this is the only factor that should be 
considered (see renal impairment section). 
 
Paediatric population (see section 4.2 and section 5.1) 
There are no data on the use of Iasibon in patients less than 18 years old. 
 
5.3 Preclinical safety data 
 
Effects in non-clinical studies were observed only at exposures sufficiently in excess of the maximum 
human exposure indicating little relevance to clinical use. As with other bisphosphonates, the kidney 
was identified to be the primary target organ of systemic toxicity. 
 
Mutagenicity/Carcinogenicity: 
No indication of carcinogenic potential was observed. Tests for genotoxicity revealed no evidence of 
effects on genetic activity for ibandronic acid. 
 
Reproductive toxicity: 
No evidence of direct foetal toxicity or teratogenic effects were observed for ibandronic acid in 
intravenously treated rats and rabbits. In reproductive studies in rats by the oral route, effects on fertility 
consisted of increased preimplantation losses at dose levels of 1 mg/kg/day and higher. In reproductive 



   26 
 

studies in rats by the intravenous route, ibandronic acid decreased sperm counts at doses of 0.3 and 1 
mg/kg/day and decreased fertility in males at 1 mg/kg/day and in females at 1.2 mg/kg/day. Adverse 
effects of ibandronic acid in reproductive toxicity studies in the rat were those expected for this class of 
medicinal products (bisphosphonates). They include a decreased number of implantation sites, 
interference with natural delivery (dystocia), an increase in visceral variations (renal pelvis ureter 
syndrome) and teeth abnormalities in F1 offspring in rats. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium chloride 
Acetic acid, glacial  
Sodium acetate trihydrate 
Water for injections 
 
6.2 Incompatibilities 
 
To avoid potential incompatibilities Iasibon concentrate for solution for infusion should only be diluted 
with isotonic sodium chloride solution or 5% glucose solution. 
 
Iasibon should not be mixed with calcium containing solutions. 
 
6.3 Shelf life 
 
5 years.  
After reconstitution: 24 hours. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions prior to reconstitution. 
After reconstitution: Store at 2°C - 8°C (in a refrigerator). 
 
From a microbiological point of view, the product should be used immediately. If not used immediately, 
in-use storage times and conditions prior to use are the responsibility of the user and would normally 
not be longer than 24 hours at 2 to 8 °C, unless reconstitution has taken place in controlled and 
validated aseptic conditions. 
 
6.5 Nature and contents of container 
 
Iasibon 2 mg is supplied as pack containing 1 ampoule (4 ml type I glass ampoule). 
 
6.6 Special precautions for disposal  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
The release of pharmaceuticals in the environment should be minimized. 
 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Pharmathen S.A. 
Dervenakion 6 
Pallini Attiki, 15351 
Greece 



   27 
 

 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/10/659/004 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 21 January 2011 
Date of latest renewal: 30 September 2015 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu/. 
 

http://www.ema.europa.eu/


   28 
 

1. NAME OF THE MEDICINAL PRODUCT 
 
Iasibon 6 mg concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One vial with 6 ml concentrate for solution for infusion contains 6 mg ibandronic acid (as  sodium 
monohydrate). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate for solution for infusion.  
Clear, colourless solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Iasibon is indicated in adults for: 
 
- Prevention of skeletal events (pathological fractures, bone complications requiring radiotherapy 

or surgery) in patients with breast cancer and bone metastases 
 

- Treatment of tumour-induced hypercalcaemia with or without metastases 
 
4.2 Posology and method of administration 
 
Iasibon therapy should only be initiated by physicians experienced in the treatment of cancer.  
 
Posology 
Prevention of skeletal events in patients with breast cancer and bone metastases 
 
The recommended dose for prevention of skeletal events in patients with breast cancer and bone 
metastases is 6 mg intravenous injection given every 3-4 weeks. The dose should be infused over at 
least 15 minutes.  
A shorter (i.e. 15 min) infusion time should only be used for patients with normal renal function or mild 
renal impairment. There are no data available characterising the use of a shorter infusion time in 
patients with creatinine clearance below 50 ml/min. Prescribers should consult the section Patients with 
Renal Impairment (see section 4.2) for recommendations on dosing and administration in this patient 
group. 
 
Treatment of tumour-induced hypercalcaemia 
 
Prior to treatment with Iasibon the patient should be adequately rehydrated with 9 mg/ml (0.9%) sodium 
chloride solution. Consideration should be given to the severity of the hypercalcaemia as well as the 
tumour type. In general patients with osteolytic bone metastases require lower doses than patients with 
the humoral type of hypercalcaemia. In most patients with severe hypercalcaemia (albumin-corrected 
serum calcium* ≥3 mmol/l or ≥12 mg/dl) 4 mg is an adequate single dose. In patients with moderate 
hypercalcaemia (albumin-corrected serum calcium <3 mmol/l or <12 mg/dl) 2 mg is an effective dose. 
The highest dose used in clinical trials was 6 mg but this dose does not add any further benefit in terms 
of efficacy. 
 



   29 
 

* Note albumin-corrected serum calcium concentrations are calculated as follows: 
 
 Albumin-corrected serum calcium (mmol/l) = serum calcium (mmol/l) - [0.02 x albumin (g/l)] + 0.8 

or 
Albumin-corrected serum calcium (mg/dl) =serum calcium (mg/dl) + 0.8 x [4 - albumin (g/dl)] 
 
To convert the albumin-corrected serum calcium in mmol/l value to mg/dl, multiply by 4. 
 
In most cases a raised serum calcium level can be reduced to the normal range within 7 days. The 
median time to relapse (return of albumin-corrected serum calcium to levels above 3 mmol/l) was 18 - 
19 days for the 2 mg and 4 mg doses. The median time to relapse was 26 days with a dose of 6 mg. 
 
A limited number of patients (50 patients) have received a second infusion for hypercalcaemia. 
Repeated treatment may be considered in case of recurrent hypercalcaemia or insufficient efficacy. 
 
Iasibon concentrate for solution for infusion should be administered as an intravenous infusion over 2 
hours. 
 
Special populations 
Patients with hepatic impairment 
No dose adjustment is required (see section 5.2). 
 
Patients with renal impairment 
For patients with mild renal impairment (CLcr ≥50 and <80 mL/min) no dose adjustment is necessary. 
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 Volume 

1 and Time 2 

≥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. 
 
Elderly population (> 65 years) 
No dose adjustment is required (see section 5.2). 
 
Paediatric population 
The safety and efficacy of Iasibon in children and adolescents below the age of 18 years have not been 
established. No data are available . (see section 5.1 and section 5.2). 
 
Method of administration 
For intravenous administration. 
 
The content of the vial is to be used as follows: 
 



   30 
 

• Prevention of Skeletal Events - added to 100 ml isotonic sodium chloride solution or 100 ml 5% 
dextrose solution and infused over at least 15 minutes. See also dose section above for patients with 
renal impairment 
 
• Treatment of tumour-induced hypercalcaemia - added to 500 ml isotonic sodium chloride 
solution or 500 ml 5% dextrose solution and infused over 2 hours 
 
For single use only. Only clear solution without particles should be used. 
Iasibon concentrate for solution for infusion should be administered as an intravenous infusion.  
Care must be taken not to administer Iasibon concentrate for solution for infusion via intra-arterial or 
paravenous administration, as this could lead to tissue damage. 
 
4.3 Contraindications 
 
- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 
- Hypocalcaemia  
 
 
4.4 Special warnings and precautions for use 
 
Patients with disturbances of bone and mineral metabolism  
Hypocalcaemia and other disturbances of bone and mineral metabolism should be effectively treated 
before starting Iasibon therapy for metastatic bone disease.  
 
Adequate intake of calcium and vitamin D is important in all patients. Patients should receive 
supplemental calcium and/or vitamin D if dietary intake is inadequate 
 
Anaphylactic reaction/shock 
Cases of anaphylactic reaction/shock, including fatal events, have been reported in patients treated with 
intravenous ibandronic acid. 
Appropriate medical support and monitoring measures should be readily available when Iasibon 
intravenous injection is administered. If anaphylactic or other severe hypersensitivity/allergic reactions 
occur, immediately discontinue the injection and initiate appropriate treatment. 
 
Osteonecrosis of the jaw  
Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including 
osteomyelitis) has been reported in patients with cancer receiving treatment regimens including 
primarily intravenously administered bisphosphonates. Many of these patients were also receiving 
chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in patients with 
osteoporosis receiving oral bisphosphonates.  
 
A dental examination with appropriate preventive dentistry should be considered prior to treatment with 
bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, radiotherapy, 
corticosteroids, poor oral hygiene).  
 
While on treatment, these patients should avoid invasive dental procedures if possible. For patients who 
develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the 
condition. For patients requiring dental procedures, there are no data available to suggest whether 
discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. Clinical 
judgement of the treating physician should guide the management plan of each patient based on 
individual benefit/risk assessment. 
 
Osteonecrosis of the external auditory canal 
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 



   31 
 

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 
Atypical subtrochanteric and diaphyseal femoral fractures have been reported with bisphosphonate 
therapy, primarily in patients receiving long-term treatment for osteoporosis. These transverse or short 
oblique fractures can occur anywhere along the femur from just below the lesser trochanter to just above 
the supracondylar flare. These fractures occur after minimal or no trauma and some patients experience 
thigh or groin pain, often associated with imaging features of stress fractures, weeks to months before 
presenting with a completed femoral fracture. Fractures are often bilateral; therefore the contralateral 
femur should be examined in bisphosphonate-treated patients who have sustained a femoral shaft 
fracture. Poor healing of these fractures has also been reported. Discontinuation of bisphosphonate 
therapy in patients suspected to have an atypical femur fracture should be considered pending 
evaluation of the patient, based on an individual benefit risk assessment. 
During bisphosphonate treatment patients should be advised to report any thigh, hip or groin pain and 
any patient presenting with such symptoms should be evaluated for an incomplete femur fracture. 
 
Patients with renal impairment  
Clinical studies have not shown any evidence of deterioration in renal function with long term Iasibon 
therapy. Nevertheless, according to clinical assessment of the individual patient, it is recommended that 
renal function, serum calcium, phosphate and magnesium should be monitored in patients treated with 
Iasibon (see section 4.2). 
 
Patients with hepatic impairment  
As no clinical data are available, dose recommendations cannot be given for patients with severe hepatic 
insufficiency(see section 4.2). . 
 
Patients with cardiac impairment  
Overhydration should be avoided in patients at risk of cardiac failure. 
 
Patients with known hypersensitivity to other bisphosphonates 
Caution is to be taken in patients with known hypersensitivity to other bisphosphonates. 
 
Excipients with known effect 
 
Iasibon contains less than 1 mmol sodium (23 mg) per vial, i.e. essentially sodium free. 

 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Metabolic interactions are not considered likely, since ibandronic acid does not inhibit the major human 
hepatic P450 isoenzymes and has been shown not to induce the hepatic cytochrome P450 system in rats 
(see section 5.2). Ibandronic acid is eliminated by renal excretion only and does not undergo any 
biotransformation. 
 
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. 
 
4.6 Fertility, pregnancy and lactation 
 
Pegnancy 
There are no adequate data from the use of ibandronic acid in pregnant women. Studies in rats have 
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Therefore, 
Iasibon should not be used during pregnancy. 
 
Breast –feeding 



   32 
 

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. Iasibon should not be used during breast-feeding. 
 
Fertility 
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 (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
On the basis of the pharmacodynamic and pharmacokinetic profile and reported adverse reactions, it is 
expected that Iasibon has no or negligible influence on the ability to drive and use machines.  
 
4.8 Undesirable effects 
 
Summary of the safety profile 
The most serious reported adverse reactions are anaphylactic reaction/shock, atypical fractures of the 
femur, osteonecrosis for the jaw and ocular inflammation (see paragraph “description of selected 
adverse reactions” and section 4.4). 
Treatment of tumour induced hypercalcaemia is most frequently associated with a rise in body 
temperature. Less frequently,  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. 
 
Tabulated list of adverse reactions 
Table 1 lists 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. 
 
Table 1 Adverse Reactions  Reported for Intravenous Administration of Ibandronic Acid 
 
 
System Organ 
Class 

Very 
common 

Common Uncommon Rare Very rare Not known 

Infections and 
infestations 

 Infection Cystitis, 
vaginitis, oral 
candidiasis 

   

Neoplasms 
benign, 
malignant, 
and 
unspecified 

  Benign skin 
neoplasm 

   

Blood and 
lymphatic 
system 
disorders 

  Anaemia, blood 
dyscrasia 

   



   33 
 

 
System Organ 
Class 

Very 
common 

Common Uncommon Rare Very rare Not known 

Immune 
system 
disorders 

    Hypersensitivity†, 
bronchospasm†, 
angioedema† 
anaphylactic 
reaction/shock†** 

Asthma 
exacerbation 

Endocrine 
disorders 

 Parathyroid 
disorder 

    

Metabolism 
and nutrition 
disorders 

 Hypocalcaemia*
* 

Hypophosphatae
mia 

   

Psychiatric 
disorders 

  Sleep disorder, 
anxiety, 
affection lability 

   

Nervous 
system 
disorders 

 Headache, 
dizziness, 
dysgeusia (taste 
perversion) 

Cerebrovascular 
disorder, nerve 
root lesion , 
amnesia, 
migraine, 
neuralgia, 
hypertonia, 
hyperaestesia, 
paraesthesia 
circumoral, 
parosmia 

   

Eye disorders  Cataract  Ocular 
inflamma
tion†** 

  

Ear and 
labyrinth 
disorders 

  Deafness    

Cardiac 
disorders 

 Bundle branch 
block 

Myocardial 
ischaemia, 
cardiovascular 
disorder, 
palpitations 

   

Respiratory, 
thoracic, and 
mediastinal 
disorders 

 Pharyngitis Lung oedema, 
stridor 

   

Gastrointestin
al disorders 

 Diarrhoea, 
vomiting, 
dyspepsia, 
gastrointestinal 
pain, tooth 
disorder 

Gastroenteritis, 
gastritis, mouth 
ulceration, 
dysphagia, 
cheilitis 

   

Hepatobiliary 
disorders 

  Cholelithiasis    

Skin and 
subcutaneous 
tissue 
disorders 

 Skin disorder, 
ecchymosis 

Rash, alopecia  Stevens-Johnson 
Syndrome†, 
Erythema 
Multiforme†, 
Dermatitis 
Bullous† 

 



   34 
 

 
System Organ 
Class 

Very 
common 

Common Uncommon Rare Very rare Not known 

Musculoskelet
al and 
connective 
tissue 
disorders 

 Osteoarthritis, 
myalgia, 
arthralgia, joint 
disorder, bone 
pain 

 Atypical 
subtrocha
nteric and 
diaphysea
l femoral 
fractures†  

Osteonecrosis of 
jaw†**, 
osteonecrosis of 
the external 
auditory canal 
(bisphosphonate 
class adverse 
reaction) 

 

Renal and 
urinary 
disorders 

  Urinary 
retention, renal 
cyst 

   

Reproductive 
system and 
breast 
disorders 

  Pelvic pain    

General 
disorders and 
administration 
site conditions 

 Pyrexia, 
influenza-like 
illness**, 
oedema 
peripheral, 
asthenia, thirst 

Hypothermia    

Investigations  Gamma-GT 
increased, 
creatinine 
increased 

Blood alkaline 
phosphatase 
increase, weight 
decrease 

   

Injury, 
poisoning and 
procedural 
complications 

  Injury, injection 
site pain 

   

**See further information below 
†Identified in postmarketing experience. 
 
Description of selected adverse reactions 
 
Hypocalcaemia 
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. 
 
Influenza-like illness 
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. 
 
Osteonecrosis of jaw 
Osteonecrosis of the jaw has been reported in patients treated by bisphosphonates. The majority of the 
reports refer to cancer patients, but such cases have also been reported in patients treated for 
osteoporosis. Osteonecrosis of the jaw is generally associated with tooth extraction and/or local 
infection (including osteomyelitis). Diagnosis of cancer, chemotherapy, radiotherapy, corticosteroids 
and poor oral hygiene are also deemed as risk factors (see section 4.4). 
 
Ocular inflammation 
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. 
 
Anaphylactic reaction/shock 



   35 
 

Cases of anaphylactic reaction/shock, including fatal events, have been reported in patients treated with 
intravenous ibandronic acid. 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system listed 
in Appendix V. 
 
4.9 Overdose 
 
Up to now there is no experience of acute poisoning with Iasibon concentrate for solution for infusion. 
Since both the kidney and the liver were found to be target organs for toxicity in preclinical studies with 
high doses, kidney and liver function should be monitored. Clinically relevant hypocalcaemia should be 
corrected by intravenous administration of calcium gluconate. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmaco-therapeutic group: Medicinal products for treatment of bone diseases, bisphosphonate, ATC 
Code: M05BA06 
 
Ibandronic acid belongs to the bisphosphonate group of compounds which act specifically on bone. 
Their selective action on bone tissue is based on the high affinity of bisphosphonates for bone mineral. 
Bisphosphonates act by inhibiting osteoclast activity, although the precise mechanism is still not clear. 
 
In vivo, ibandronic acid prevents experimentally-induced bone destruction caused by cessation of 
gonadal function, retinoids, tumours or tumour extracts. The inhibition of endogenous bone resorption 
has also been documented by 45Ca kinetic studies and by the release of radioactive tetracycline 
previously incorporated into the skeleton. 
 
At doses that were considerably higher than the pharmacologically effective doses, ibandronic acid did 
not have any effect on bone mineralisation. 
 
Bone resorption due to malignant disease is characterised by excessive bone resorption that is not 
balanced with appropriate bone formation. Ibandronic acid selectively inhibits osteoclast activity, 
reducing bone resorption and thereby reducing skeletal complications of the malignant disease. 
 
Clinical studies in the treatment of tumour-induced hypercalcaemia 
Clinical studies in hypercalcaemia of malignancy demonstrated that the inhibitory effect of ibandronic 
acid on tumour-induced osteolysis, and specifically on tumour-induced hypercalcaemia, is characterised 
by a decrease in serum calcium and urinary calcium excretion. 
 
In the dose range recommended for treatment, the following response rates with the respective 
confidence intervals have been shown in clinical trials for patients with baseline albumin-corrected 
serum calcium ≥ 3.0 mmol/l after adequate rehydration. 
 
Ibandronic 
acid dose 

% of Patients with 
Response 

90% Confidence 
Interval 

2 mg 54 44-63 

4 mg 76 62-86 

6 mg 78 64-88 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


   36 
 

 
For these patients and dosages, the median time to achieve normocalcaemia was 4 to 7 days. The 
median time to relapse (return of albumin-corrected serum calcium above 3.0 mmol/l) was 18 to 26 
days. 
 
Clinical studies in the prevention of skeletal events in patients with breast cancer and bone metastases 
Clinical studies in patients with breast cancer and bone metastases have shown that there is a dose 
dependent inhibitory effect on bone osteolysis, expressed by markers of bone resorption, and a dose 
dependent effect on skeletal events. 
 
Prevention of skeletal events in patients with breast cancer and bone metastases with Ibandronate 6 mg 
administered intravenously was assessed in one randomized placebo controlled phase III trial with a 
duration of 96 weeks. Female patients with breast cancer and radiologically confirmed bone metastases 
were randomised to receive placebo (158 patients) or 6 mg Ibandronate (154 patients). The results from 
this trial are summarised below. 
 
Primary efficacy endpoints 
The primary endpoint of the trial was the skeletal morbidity period rate (SMPR). This was a composite 
endpoint which had the following skeletal related events (SREs) as sub-components: 

 
- radiotherapy to bone for treatment of fractures/impending fractures 
- surgery to bone for treatment of fractures 
- vertebral fractures 
- non-vertebral fractures 
 
The analysis of the SMPR was time-adjusted and considered that one or more events occurring in a 
single 12 week period could be potentially related. Multiple events were therefore counted only once for 
the purposes of the analysis. Data from this study demonstrated a significant advantage for intravenous 
Ibandronate 6 mg over placebo in the reduction in SREs measured by the time-adjusted SMPR 
(p=0.004). The number of SREs was also significantly reduced with Ibandronate 6 mg and there was a 
40% reduction in the risk of a SRE over placebo (relative risk 0.6, p = 0.003). Efficacy results are 
summarised in table 2. 
 
Table 2 Efficacy Results (Breast Cancer Patients with Metastatic Bone Disease) 
 
 All Skeletal Related Events (SREs) 

Placebo 
n=158 

Ibandronate 6 mg 
n=154 

p-value 

SMPR (per patient year) 1.48 1.19 p=0.004 

Number of events (per 
patient) 

3.64 2.65 p=0.025 

SRE relative risk - 0.60 p=0.003 

 
Secondary efficacy endpoints 
A statistically significant improvement in bone pain score was shown for intravenous Ibandronate 6 mg 
compared to placebo. The pain reduction was consistently below baseline throughout the entire study 
and accompanied by a significantly reduced use of analgesics. The deterioration in Quality of Life was 
significantly less in Ibandronate treated patients compared with placebo. A tabular summary of these 
secondary efficacy results is presented in table 3. 
 
Table 3 Secondary efficacy results (breast cancer patients with metastatic bone disease) 
 



   37 
 

 Placebo 
n=158 

Ibandronatebandro
nate 6 mg 
n=154 

p-value 

Bone pain * 0.21 -0.28 p<0.001 

Analgesic use * 0.90 0.51 p=0.083 

Quality of Life * -45.4 -10.3 p=0.004 

*Mean change from baseline to last assessment. 
 
There was a marked depression of urinary markers of bone resorption (pyridinoline and 
deoxypyridinoline) in patients treated with Ibandronate that was statistically significant compared to 
placebo. 
 
In a study in 130 patients with metastatic breast cancer the safety of Ibandronate infused over 1 hour or 
15 minutes was compared. No difference was observed in the indicators of renal function. The overall 
adverse event profile of ibandronic acid following the 15 minute infusion was consistent with the 
known safety profile over longer infusion times and no new safety concerns were identified relating to 
the use of a 15 minute infusion time. 
 
A 15 minute infusion time has not been studied in cancer patients with a creatinine clearance of 
<50 ml/min. 
 
Paediatric population (see section 4.2 and section 5.2) 
The safety and efficacy of Iasibon in children and adolescents below the age of 18 years have not been 
established. No data are available. 
 
5.2 Pharmacokinetic properties 
 
After a 2 hour infusion of 2, 4 and 6 mg ibandronic acid pharmacokinetic parameters are dose 
proportional. 
 
Distribution 
After initial systemic exposure, ibandronic acid rapidly binds to bone or is excreted into urine. In 
humans, the apparent terminal volume of distribution is at least 90 l and the amount of dose reaching the 
bone is estimated to be 40-50% of the circulating dose. Protein binding in human plasma is 
approximately 87% at therapeutic concentrations, and thus interaction with other medicinal products, 
due to displacement is unlikely. 
 
Biotransformation 
There is no evidence that ibandronic acid is metabolized in animals or humans. 
 
Elimination 
The range of observed apparent half-lives is broad and dependent on dose and assay sensitivity, but the 
apparent terminal half-life is generally in the range of 10-60 hours. However, early plasma levels fall 
quickly, reaching 10% of peak values within 3 and 8 hours after intravenous or oral administration 
respectively. No systemic accumulation was observed when ibandronic acid was administered 
intravenously once every 4 weeks for 48 weeks to patients with metastatic bone disease. 
 
Total clearance of ibandronic acid is low with average values in the range 84-160 ml/min. Renal 
clearance (about 60 ml/min in healthy postmenopausal females) accounts for 50-60% of total clearance 
and is related to creatinine clearance. The difference between the apparent total and renal clearances is 
considered to reflect the uptake by bone. 
 
The secretory pathway of renal elimination does not appear to include known acidic or basic transport 



   38 
 

systems involved in the excretion of other active substances. In addition, ibandronic acid does not 
inhibit the major human hepatic P450 isoenzymes and does not induce the hepatic cytochrome P450 
system in rats. 
 
 
Pharmacokinetics in special populations 
 
Gender 
Bioavailability and pharmacokinetics of ibandronic acid are similar in both men and women. 
 
Race 
There is no evidence for clinically relevant interethnic differences between Asians and Caucasians in 
ibandronic acid disposition. There are only very few data available on patients with African origin. 
 
Patients with renal impairment 
Exposure to ibandronic acid in patients with various degrees of renal impairment is related to creatinine 
clearance (CLcr). In subjects with severe renal impairment (mean estimated CLcr = 21.2 mL/min), 
dose-adjusted mean AUC0-24h was increased by 110% compared to healthy volunteers. In clinical 
pharmacology trial WP18551, after a single dose intravenous administration of 6 mg (15 minutes 
infusion), mean AUC0-24 increased by 14% and 86%, respectively, in subjects with mild (mean 
estimated CLcr=68.1 mL/min) and moderate (mean estimated CLcr=41.2 mL/min) renal impairment 
compared to healthy volunteers (mean estimated CLcr=120 mL/min). Mean Cmax was not increased in 
patients with mild renal impairment and increased by 12% in patients with moderate renal impairment. 
For patients with mild renal impairment (CLcr ≥50 and <80 mL/min) no dosage adjustment is 
necessary. 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 an adjustment in the dose is recommended (see section 4.2). 
 
Patients with hepatic impairment (see section 4.2) 
There are no pharmacokinetic data for ibandronic acid in patients who have hepatic impairment. The 
liver has no significant role in the clearance of ibandronic acid since it is not metabolized but is 
cleared by renal excretion and by uptake into bone. Therefore dosage adjustment is not necessary in 
patients with hepatic impairment. Further, as protein binding of ibandronic acid is approximately 87% at 
therapeutic concentrations, hypoproteinaemia in severe liver disease is unlikely to lead to clinically 
significant increases in free plasma concentration. 
 
Elderly (see section 4.2) 
In a multivariate analysis, age was not found to be an independent factor of any of the pharmacokinetic 
parameters studied. As renal function decreases with age, this is the only factor that should be 
considered (see renal impairment section). 
 
Paediatric population (see section 4.2 and section 5.1) 
There are no data on the use of Iasibon in patients less than 18 years old. 
 
5.3 Preclinical safety data 
Effects in non-clinical studies were observed only at exposures sufficiently in excess of the maximum 
human exposure indicating little relevance to clinical use. As with other bisphosphonates, the kidney 
was identified to be the primary target organ of systemic toxicity. 
 
Mutagenicity/Carcinogenicity: 
No indication of carcinogenic potential was observed. Tests for genotoxicity revealed no evidence of 
effects on genetic activity for ibandronic acid. 
 
Reproductive toxicity: 
No evidence of direct foetal toxicity or teratogenic effects were observed for ibandronic acid in 
intravenously treated rats and rabbits. In reproductive studies in rats by the oral route, effects on fertility 
consisted of increased preimplantation losses at dose levels of 1 mg/kg/day and higher. In reproductive 



   39 
 

studies in rats by the intravenous route, ibandronic acid decreased sperm counts at doses of 0.3 and 1 
mg/kg/day and decreased fertility in males at 1 mg/kg/day and in females at 1.2 mg/kg/day. Adverse 
effects of ibandronic acid in reproductive toxicity studies in the rat were those expected for this class of 
medicinal products (bisphosphonates). They include a decreased number of implantation sites, 
interference with natural delivery (dystocia), an increase in visceral variations (renal pelvis ureter 
syndrome) and teeth abnormalities in F1 offspring in rats. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium chloride 
Acetic acid, glacial  
Sodium acetate trihydrate 
Water for injections 
 
6.2 Incompatibilities 
 
To avoid potential incompatibilities Iasibon concentrate for solution for infusion should only be diluted 
with isotonic sodium chloride solution or 5% glucose solution. 
 
Iasibon should not be mixed with calcium containing solutions. 
 
6.3 Shelf life 
 
5 years.  
After reconstitution: 24 hours. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions prior to reconstitution. 
After reconstitution: Store at 2°C - 8°C (in a refrigerator). 
 
From a microbiological point of view, the product should be used immediately. If not used immediately, 
in-use storage times and conditions prior to use are the responsibility of the user and would normally 
not be longer than 24 hours at 2 to 8 °C, unless reconstitution has taken place in controlled and 
validated aseptic conditions. 
 
6.5 Nature and contents of container 
 
Iasibon 6 mg is supplied as packs containing 1,5,10 vials (9 ml type I glass vial with a bromobutyl 
rubber stopper). 
 
6.6 Special precautions for disposal  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
The release of pharmaceuticals in the environment should be minimized. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Pharmathen S.A. 
Dervenakion 6 
Pallini Attiki, 15351 
Greece 



   40 
 

 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/10/659/005 
EU/1/10/659/006 
EU/1/10/659/007 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 21 January 2011 
Date of latest renewal: 30 September 2015 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu/.

http://www.ema.europa.eu/


   41 
 

1. NAME OF THE MEDICINAL PRODUCT 
 
Iasibon 50 mg film coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 50 mg of ibandronic acid (as sodium monohydrate).  
 
Excipients with known effect: 
Contains 0.86 mg lactose (as lactose monohydrate).  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablets. 
White round biconvex tablets 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Iasibon is indicated in adults for the prevention of skeletal events (pathological fractures, bone 
complications requiring radiotherapy or surgery) in patients with breast cancer and bone metastases. 
 
4.2 Posology and method of administration 
 
Iasibon therapy should only be initiated by physicians experienced in the treatment of cancer.  
 
Posology 
The recommended dose is one 50 mg film-coated tablet daily. 
 
Special populations 
Patients with hepatic impairment 
No dose adjustment is required (see section 5.2 ). 
 
Patients with renal impairment 
No dose adjustment is necessary for patients with mild renal impairment (CLcr ≥50 and <80 mL/min). 
 
For patients with moderate renal impairment (CLcr ≥30 and <50 mL/min) a dosage adjustment to one 
50 mg film-coated tablet every second day is recommended (see section 5.2). 
 
For patients with severe renal impairment (CLcr <30 mL/min) the recommended dose is one 50 mg 
film-coated tablet once weekly. See dosing instructions, above. 
 
Elderly population (> 65 years) 
No dose adjustment is necessary (see section 5.2). 
 
 Paediatric population 
The safety and efficacy of Iasibonin children and adolescents below the age of 18 years have not been 
established. No data are available (see section 5.1 and 5.2). 
 
Method of administration 
For oral use. 



   42 
 

 
Iasibon tablets should be taken after an overnight fast (at least 6 hours) and before the first food or drink 
of the day. Medicinal products and supplements (including calcium) should similarly be avoided prior 
to taking Iasibon tablets. Fasting should be continued for at least 30 minutes after taking the tablet.  
Water may be taken at any time during the course of Iasibon treatment (see section 4.5). Water with a 
high concentration of calcium should not be used. If there is concern regarding potentially high levels of 
calcium in the tap water (hard water), it is advised to use bottled water with a low mineral content. 
 
 
- The tablets should be swallowed whole with a full glass of water (180 to 240 ml) while the 

patient is standing or sitting in an upright position. 
 
- Patients should not lie down for 60 minutes after taking Iasibon. 
 
- Patients should not chew, suck or crush the tablet because of a potential for oropharyngeal 

ulceration.  
 
- Water is the only drink that should be taken with Iasibon.  
 
4.3 Contraindications 
 
- Hypersensitivity to ibandronic acid or to any of the excipients listed in section 6.1.  
- Hypocalcaemia 
- Abnormalities of the oesophagus which delay oesophageal emptying such as stricture or achalasia 
- Inability to stand or sit upright for at least 60 minutes 
 
4.4 Special warnings and precautions for use 
 
Patients with disturbances of bone and mineral metabolism  
Hypocalcaemia and other disturbances of bone and mineral metabolism should be effectively treated 
before starting Iasibon therapy. Adequate intake of calcium and vitamin D is important in all patients. 
Patients should receive supplemental calcium and/or vitamin D if dietary intake is inadequate. 
 
Gastrointestinal irritation 
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 Iasibon 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 (see section 4.2). 
Physicians should be alert to any signs or symptoms signaling a possible oesophageal reaction and 
patients should be instructed to discontinue Iasibon 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.  
 
Acetylsalicylic acid and NSAIDs  
Since Acetylsalicylic acid, Nonsteroidal Anti-Inflammatory medicinal products (NSAIDS) and 
bisphosphonates are associated with gastrointestinal irritation, caution should be taken during 
concomitant administration. 



   43 
 

 
Osteonecrosis of the jaw  
Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including 
osteomyelitis), has been reported in patients with cancer receiving treatment regimens including 
primarily intravenously administered bisphosphonates. Many of these patients were also receiving 
chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in patients with 
osteoporosis receiving oral bisphosphonates. 
 
A dental examination with appropriate preventive dentistry should be considered prior to treatment with 
bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, radiotherapy, 
corticosteroids, poor oral hygiene). 
 
While on treatment, these patients should avoid invasive dental procedures if possible. For patients who 
develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the 
condition. For patients requiring dental procedures, there are no data available to suggest whether 
discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. Clinical 
judgement of the treating physician should guide the management plan of each patient based on 
individual benefit/risk assessment. 
 
Osteonecrosis of the external auditory canal 
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. 
 
Atypical fractures of the femur 
Atypical subtrochanteric and diaphyseal femoral fractures have been reported with bisphosphonate 
therapy, primarily in patients receiving long-term treatment for osteoporosis. These transverse or short 
oblique fractures can occur anywhere along the femur from just below the lesser trochanter to just above 
the supracondylar flare. These fractures occur after minimal or no trauma and some patients experience 
thigh or groin pain, often associated with imaging features of stress fractures, weeks to months before 
presenting with a completed femoral fracture. Fractures are often bilateral; therefore the contralateral 
femur should be examined in bisphosphonate-treated patients who have sustained a femoral shaft 
fracture. Poor healing of these fractures has also been reported.  
 
Discontinuation of bisphosphonate therapy in patients suspected to have an atypical femur fracture 
should be considered pending evaluation of the patient, based on an individual benefit risk assessment. 
 
During bisphosphonate treatment patients should be advised to report any thigh, hip or groin pain and 
any patient presenting with such symptoms should be evaluated for an incomplete femur fracture. 
 
Renal function 
Clinical studies have not shown any evidence of deterioration in renal function with long term Iasibon 
therapy. Nevertheless, according to clinical assessment of the individual patient, it is recommended that 
renal function, serum calcium, phosphate and magnesium should be monitored in patients treated with 
Iasibon. 
 
Rare hereditary problems  
Iasibon tablets contain lactose and should not be administered to patients with rare hereditary problems 
of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. 
 
Patients with known hypersensitivity to other bisphosphonates 
Caution is to be taken in patients with known hypersensitivity to other bisphosphonates. 



   44 
 

 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Medicinal product -Food Interactions 
Products containing calcium and other multivalent cations (such as aluminium, magnesium, iron), 
including milk and food, are likely to interfere with absorption of Iasibon tablets. Therefore, with 
such products, including food, intake must be delayed at least 30 minutes following oral 
administration. 
 
Bioavailability was reduced by approximately 75% when Iasibon tablets were administered 2 hours 
after a standard meal. Therefore, it is recommended that the tablets should be taken after an overnight 
fast (at least 6 hours) and fasting should continue for at least 30 minutes after the dose has been taken 
(see section 4.2). 
 
Interactions with other medicinal products 
 
Metabolic interactions are not considered likely, since ibandronic acid does not inhibit the major human 
hepatic P450 isoenzymes and has been shown not to induce the hepatic cytochrome P450 system in rats 
(see section 5.2). Ibandronic acid is eliminated by renal excretion only and does not undergo any 
biotransformation.  
 
H2-antagonists or other medicinal products that increase gastric pH. 
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 Iasibon is administered with H2-antagonists or medicinal products that 
increase gastric pH. 
 
Acetylsalicylic acid and NSAIDs  
Since Acetylsalicylic acid, Nonsteroidal Anti-Inflammatory medicinal products (NSAIDs) and 
bisphosphonates are associated with gastrointestinal irritation, caution should be taken during 
concomitant administration (see section 4.4). 
 
Aminoglycosides 
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. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
There are no adequate data from the use of ibandronic acid in pregnant women. Studies in rats have 
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Therefore, 
Iasibon should not be used during pregnancy. 
 
Breast-feeding 
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. Iasibon should not be used during breast-feeding. 
 
Fertility 
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 (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 



   45 
 

On the basis of the pharmacodynamic and pharmacokinetic profile and reported adverse reactions, it is 
expected that Iasibon has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
Summary of the safety profile 
The most serious reported adverse reactions are anaphylactic reaction/shock, atypical fractures of the 
femur, osteonecrosis of the jaw, gastrointestinal irritation, and ocular inflammation (see paragraph 
“Description of selected adverse reactions” and section 4.4). 
 
Treatment was most frequently associated with a decrease in serum calcium to below normal range 
(hypocalcaemia), followed by dyspepsia. 
 
Tabulated list of adverse reactions 
Table 1 lists 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. 
 
Table 1 Adverse Drug Reactions Reported for Oral Administration of Ibandronate 
 
 

System 
Organ Class 

Very 
common 

Common Uncommon Rare Very rare Not known 

Blood and 
lymphatic 
system 
disorders 

  Anaemia    

Immune 
system 
disorders 

    Hypersensitivity
†, 
bronchospasm†, 
angioedema†, 
Anaphylactic 
reaction/shock†
** 

Asthma 
exacerbation 

Metabolism 
and nutrition 
disorders 

 Hypocalcaemia
** 

    

Nervous 
system 
disorders 

  Paraesthesia, 
dysgeusia 
(taste 
perversion) 

   



   46 
 

 

System 
Organ Class 

Very 
common 

Common Uncommon Rare Very rare Not known 

Eye disorders    Ocular 
inflam
mation
†** 

  

Gastrointesti
nal disorders 

 Oesophagitis, 
abdominal pain, 
dyspepsia, 
nausea 

Haemorrage, 
duodenal 
ulcer, 
gastritis, 
dysphagia, 
dry mouth 

   

Skin and 
subcutaneous 
tissue 
disorders 

  Pruritus  Stevens-Johnson 
Syndrome†, 
Erythema 
Multiforme†, 
Dermatitis 
Bullous† 

 

Musculoskele
tal and 
connective 
tissue 
disorders 

   Atypic
al 
subtro
chante
ric and 
diaphy
seal 
femor
al 
fractur
es†  

Osteonecrosis of 
jaw†**, 
osteonecrosis of 
the external 
auditory canal 
(bisphosphonate 
class adverse 
reaction) 

 

Renal and 
urinary 
disorders 

  Azotaemia 
(uraemia) 

   

General 
disorders and 
administratio
n site 
conditions 

 Asthenia Chest pain, 
influenza-
like illness, 
malaise, pain 

   

Investigations   Blood 
parathyroid 
hormone 
increased 

   

**See further information below 



   47 
 

†Identified in postmarketing experience. 
 
Description of selected adverse reactions 
 
Hypocalcaemia 
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. 
 
 
Osteonecrosis of jaw 
Osteonecrosis of the jaw has been reported in patients treated by bisphosphonates. The majority of the 
reports refer to cancer patients, but such cases have also been reported in patients treated for 
osteoporosis. Osteonecrosis of the jaw is generally associated with tooth extraction and / or local 
infection (including osteomyelitis). Diagnosis of cancer, chemotherapy, radiotherapy, corticosteroids 
and poor oral hygiene are also deemed as risk factors (see section 4.4). 
 
Ocular inflammation 
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. 
 
Anaphylactic reaction/shock 
Cases of anaphylactic reaction/shock, including fatal events, have been reported in patients treated with 
intravenous ibandronic acid. 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system listed 
in Appendix V. 
 
4.9 Overdose 
 
No specific information is available on the treatment of overdosage with Iasibon. However, oral 
overdosage may result in upper gastrointestinal events, such as upset stomach, heartburn, oesophagitis, 
gastritis or ulcer. Milk or antacids should be given to bind Iasibon. Due to the risk of oesophageal 
irritation, vomiting should not be induced and the patient should remain fully upright. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmaco-therapeutic group: Medicinal products for treatment of bone diseases, bisphosphonate, ATC 
Code: M05BA06 
 
Ibandronic acid belongs to the bisphosphonate group of compounds which act specifically on bone. 
Their selective action on bone tissue is based on the high affinity of bisphosphonates for bone mineral. 
Bisphosphonates act by inhibiting osteoclast activity, although the precise mechanism is still not clear. 
 
In vivo, ibandronic acid prevents experimentally-induced bone destruction caused by cessation of 
gonadal function, retinoids, tumours or tumour extracts. The inhibition of endogenous bone resorption 
has also been documented by45 Ca kinetic studies and by the release of radioactive tetracycline 
previously incorporated into the skeleton. 
 
At doses that were considerably higher than the pharmacologically effective doses, ibandronic acid did 
not have any effect on bone mineralisation. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


   48 
 

Bone resorption due to malignant disease is characterized by excessive bone resorption that is not 
balanced with appropriate bone formation. Ibandronic acid selectively inhibits osteoclast activity, 
reducing bone resorption and thereby reducing skeletal complications of the malignant disease. 
Clinical studies in patients with breast cancer and bone metastases have shown that there is a dose 
dependent inhibitory effect on bone osteolysis, expressed by markers of bone resorption, and a dose 
dependent effect on skeletal events. 
 
Prevention of skeletal events in patients with breast cancer and bone metastases with Ibandronate 50 mg 
tablets was assessed in two randomized placebo controlled phase III trials with a duration of 96 weeks. 
Female patients with breast cancer and radiologically confirmed bone metastases were randomised to 
receive placebo (277 patients) or 50 mg Ibandronate (287 patients). The results from these trials are 
summarised below. 
 
Primary efficacy endpoints 
The primary endpoint of the trials was the skeletal morbidity period rate (SMPR). This was a composite 
endpoint which had the following skeletal related events (SREs) as sub-components: 
 
- radiotherapy to bone for treatment of fractures/impending fractures 
- surgery to bone for treatment of fractures 
- vertebral fractures 
- non-vertebral fractures 
 
The analysis of the SMPR was time-adjusted and considered that one or more events occurring in a 
single 12 week period could be potentially related. Multiple events were therefore, counted only once in 
any given 12 week period for the purposes of the analysis. Pooled data from these studies demonstrated 
a significant advantage for Ibandronate 50 mg p.o. over placebo in the reduction in SREs measured by 
the SMPR (p=0.041). There was also a 38% reduction in the risk of developing an SRE for Ibandronate 
treated patients when compared with placebo (relative risk 0.62, p=0.003). Efficacy results are 
summarised in Table 2. 
 
Table 2 Efficacy Results (Breast Cancer Patients with Metastatic Bone Disease) 
 
 All Skeletal Related Events (SREs) 

Placebo 
n=277 

Ibandronate 50 mg 
n=287 

p-value 

SMPR (per patient year) 1.15 0.99 p=0.041 

SRE relative risk - 0.62 p=0.003 

 
Secondary efficacy endpoints 
A statistically significant improvement in bone pain score was shown for Ibandronate 50 mg compared 
to placebo. The pain reduction was consistently below baseline throughout the entire study and 
accompanied by a significantly reduced use of analgesics compared to placebo. The deterioration in 
Quality of Life and WHO performance status was significantly less in Ibandronate treated patients 
compared with placebo. Urinary concentrations of the bone resorption marker CTx (C-terminal 
telopeptide released from Type I collagen) were significantly reduced in the Ibandronate group 
compared to placebo. This reduction in urinary CTx levels was significantly correlated with the primary 
efficacy endpoint SMPR (Kendall-tau-b (p<0.001)). A tabular summary of the secondary efficacy 
results is presented in Table 3. 
 
Table 3 Secondary Efficacy Results (Breast Cancer Patients with Metastatic Bone 
  Disease) 
 
 Placebo n=277 Ibandronatebandronat

e 50 mg 
n=287 

p-value 



   49 
 

Bone pain * 0.20 -0.10 p=0.001 

Analgesic use * 0.85 0.60 p=0.019 

Quality of Life * -26.8 -8.3 p=0.032 

WHO performance 
score * 

0.54 0.33 p=0.008 

Urinary CTx ** 10.95 -77.32 p=0.001 

* Mean change from baseline to last assessment. 
** Median change from baseline to last assessment 
 
Paediatric population(see section 4.2 and section 5.2) 
The safety and efficacy of Iasibon in children and adolescents below the age of 18 years have not been 
established. No data are available. 
 
5.2 Pharmacokinetic properties 
 
Absorption 
The absorption of ibandronic acid in the upper gastrointestinal tract is rapid after oral administration. 
Maximum observed plasma concentrations were reached within 0.5 to 2 hours (median 1 hour) in the 
fasted state and absolute bioavailability was about 0.6%. The extent of absorption is impaired when 
taken together with food or beverages (other than water). Bioavailability is reduced by about 90% when 
ibandronic acid is administered with a standard breakfast in comparison with bioavailability seen in 
fasted subjects. When taken 30 minutes before a meal, the reduction in bioavailability is approximately 
30%. There is no meaningful reduction in bioavailability provided ibandronic acid is taken 60 minutes 
before a meal. 
 
Bioavailability was reduced by approximately 75% when Iasibon tablets were administered 2 hours 
after a standard meal. Therefore, it is recommended that the tablets should be taken after an overnight 
fast (minimum 6 hours) and fasting should continue for at least 30 minutes after the dose has been taken 
(see section 4.2). 
 
Distribution 
After initial systemic exposure, ibandronic acid rapidly binds to bone or is excreted into urine. In 
humans, the apparent terminal volume of distribution is at least 90 l and the amount of dose reaching the 
bone is estimated to be 40-50% of the circulating dose. Protein binding in human plasma is 
approximately 87% at therapeutic concentrations, and thusinteraction with other medicinal products, 
due to displacement is unlikely. 
 
Biotransformation 
There is no evidence that ibandronic acid is metabolized in animals or humans. 
 
Elimination 
The absorbed fraction of ibandronic acid is removed from the circulation via bone absorption (estimated 
to be 40-50%) and the remainder is eliminated unchanged by the kidney. The unabsorbed fraction of 
ibandronic acid is eliminated unchanged in the faeces. 
 
The range of observed apparent half-lives is broad and dependent on dose and assay sensitivity, but the 
apparent terminal half-life is generally in the range of 10-60 hours. However, early plasma levels fall 
quickly, reaching 10% of peak values within 3 and 8 hours after intravenous or oral administration 
respectively. 
 
Total clearance of ibandronic acid is low with average values in the range 84-160 ml/min. Renal 
clearance (about 60 ml/min in healthy postmenopausal females) accounts for 50-60% of total clearance 
and is related to creatinine clearance. The difference between the apparent total and renal clearances is 



   50 
 

considered to reflect the uptake by bone. 
 
The secretory pathway of renal elimination does not appear to include known acidic or basic transport 
systems involved in the excretion of other active substances. In addition, ibandronic acid does not 
inhibit the major human hepatic P450 isoenzymes and does not induce the hepatic cytochrome P450 
system in rats. 
 
Pharmacokinetics in special populations 
 
Gender 
Bioavailability and pharmacokinetics of ibandronic acid are similar in both men and women. 
 
Race 
There is no evidence for clinically relevant interethnic differences between Asians and Caucasians in 
ibandronic acid disposition. There are only very few data available on patients with African origin. 
 
Patients with renal impairment 
Exposure to ibandronic acid in patients with various degree of renal impairment is related to creatinine 
clearance (CLcr). Subjects with severe renal impairment (CLcr ≤ 30 mL/min) receiving oral 
administration of 10 mg ibandronic acid daily for 21 days, had 2-3 fold higher plasma concentrations 
than subjects with normal renal function (CLcr ≥80 mL/min). Total clearance of ibandronic acid was 
reduced to 44 ml/min in the subjects with severe renal impairment compared with 129 mL/min in 
subjects with normal renal function.No dosage adjustment is necessary for patients with mild renal 
impairment (CLcr ≥50 and <80 mL/min). For patients with moderate renal impairment (CLcr ≥30 and 
<50 mL/min) or severe renal impairment (CLcr <30 mL/min) an adjustment in the dose is 
recommended (see section 4.2). 
 
Patients with hepatic impairment (see section 4.2) 
There are no pharmacokinetic data for ibandronic acid in patients who have hepatic impairment. The 
liver has no significant role in the clearance of ibandronic acid since it is not metabolized but is cleared 
by renal excretion and by uptake into bone. Therefore dosage adjustment is not necessary in patients 
with hepatic impairment. Further, as protein binding of ibandronic acid is approximately 87% at 
therapeutic concentrations, hypoproteinaemia in severe liver disease is unlikely to lead to clinically 
significant increases in free plasma concentration. 
 
Elderly (see section 4.2) 
In a multivariate analysis, age was not found to be an independent factor of any of the pharmacokinetic 
parameters studied. As renal function decreases with age, this is the only factor to take into 
consideration (see renal impairment section). 
 
Paediatric population (see section 4.2 and section 5.1) 
There are no data on the use of Iasibon in patients less than 18 years old. 
 
5.3 Preclinical safety data 
 
Effects in non-clinical studies were observed only at exposures sufficiently in excess of the maximum 
human exposure indicating little relevance to clinical use. As with other bisphosphonates, the kidney 
was identified to be the primary target organ of systemic toxicity. 
 
Mutagenicity/Carcinogenicity: 
No indication of carcinogenic potential was observed. Tests for genotoxicity revealed no evidence of 
genetic activity for ibandronic acid. 
 
Reproductive toxicity: 
No evidence of direct foetal toxicity or teratogenic effects was observed for ibandronic acid in 
intravenously or orally treated rats and rabbits. In reproductive studies in rats by the oral route effects on 
fertility consisted of increased preimplantation losses at dose levels of 1 mg/kg/day and higher. In 



   51 
 

reproductive studies in rats by the intravenous route, ibandronic acid decreased sperm counts at doses of 
0.3 and 1 mg/kg/day and decreased fertility in males at 1 mg/kg/day and in females at 1.2 mg/kg/day. 
Adverse effects of ibandronic acid in reproductive toxicity studies in the rat were those expected for this 
class of medicinal products (bisphosphonates). They include a decreased number of implantation sites, 
interference with natural delivery (dystocia), an increase in visceral variations (renal pelvis ureter 
syndrome) and teeth abnormalities in F1 offspring in rats. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core: 
Povidone 
Cellulose, microcrystalline 
Crospovidone 
Maize starch pregelatinised 
Glycerol dibehenate 
Silica, anhydrous colloidal 
 
Tablet coat: 
Lactose monohydrate 
Macrogol 4000 
Hypromellose (E464) 
Titanium dioxide E171 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
5 years. 
 
6.4 Special precautions for storage 
 
Store in the original package in order to protect from moisture. 
 
6.5 Nature and contents of container 
 
Iasibon 50 mg film coated tablets are supplied in Polyamide/Al/PVC - Aluminum foil blister with 3, 6, 
9, 28 or 84 tablets, packaged in a cardboard box.  
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. The release of pharmaceuticals in the environment should be minimized. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Pharmathen S.A. 
Dervenakion 6 
15351 Pallini, Attiki 
Greece 
 



   52 
 

 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/10/659/001 
EU/1/10/659/002 
EU/1/10/659/008 
EU/1/10/659/009 
EU/1/10/659/0010 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 21 January 2011 
Date of latest renewal: 30 September 2015 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu/ 

http://www.ema.europa.eu/


   53 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND 
USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE 

SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT 



   54 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturers responsible for batch release 
 
Concentrate for solution for infusion 
 
Pharmathen S.A. 
Dervenakion 6  
Pallini 15351 
Attiki  
Greece 
 
Film-coated tablet 
 
Pharmathen S.A. 
Dervenakion 6  
Pallini 15351 
Attiki  
Greece 
 
And 
 
Pharmathen International S.A. 
Industrial Park Sapes, Street block 5 
69300 Sapes, Prefecture of Rodopi  
Greece 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION 
 
Periodic safety update reports  
 
At the time of granting the marketing authorisation, the submission of periodic safety update reports is 
not required for this medicinal product. However, the marketing authorisation holder shall submit 
periodic safety update reports for this medicinal product if the product is included in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and published 
on the European medicines web-portal. 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE 
USE OF THE MEDICINAL PRODUCT 

 
Risk Management Plan (RMP) 

 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in 
the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed 
subsequent updates of the RMP. 
 
An updated RMP should be submitted: 



   55 
 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the 
same time. 
 



   56 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
ANNEX III 

 
LABELLING AND PACKAGE LEAFLET 



   57 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



   58 
 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Outer Carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Iasibon 1 mg concentrate for solution for infusion  
ibandronic acid 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One ampoule with 1 ml concentrate for solution for infusion contains 1 mg ibandronic acid (sodium 
monohydrate). 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium chloride, glacial acetic acid, sodium acetate trihydrate and water for injections. See package 
leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion.  
1 ampoule 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Intravenous use, for infusion after dilution 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
This medicinal product does not require any special storage conditions prior to reconstitution. After 
dilution the infusion solution is stable for 24 hours at 2 °C - 8 °C (in a refrigerator) 
 



   59 
 

 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Pharmathen S.A. 
6, Dervenakion str. 
Pallini 15351, Attiki 
Greece 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/10/659/003     
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Iasibon 1 mg 

 
 

17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  



   60 
 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Ampoule 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Iasibon 1 mg concentrate for solution for infusion 
ibandronic acid 
I.V. use 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 ml  
 
 
6. OTHER 
 



   61 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
Outer Carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Iasibon 2 mg concentrate for solution for infusion  
ibandronic acid 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One ampoule with 2 ml concentrate for solution for infusion contains 2 mg ibandronic acid (as sodium 
monohydrate). 
 
 
3. LIST OF EXCIPIENTS 
 
 
Sodium acetate trihydrate sodium chloride, glacial acetic acid and water for injections. 
 
See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
 
1 ampoule 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Intravenous use, for infusion after dilution 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
This medicinal product does not require any special storage conditions prior to reconstitution.After 
dilution the infusion solution is stable for 24 hours at 2 °C - 8 °C (in a refrigerator) 



   62 
 

 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Pharmathen S.A. 
6, Dervenakion str. 
15351 Pallini, Attiki  
Greece 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/10/659/004 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Iasibon 2 mg  

 
 

17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  



   63 
 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Ampoule 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Iasibon 2 mg concentrate for solution for infusion  
ibandronic acid 
I.V. use 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
2 ml 
 
 
6. OTHER 
 



   64 
 

  
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Outer Carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Iasibon 6 mg concentrate for solution for infusion  
ibandronic acid 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One vial with 6 ml concentrate for solution for infusion contains 6 mg ibandronic acid (as sodium 
monohydrate). 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium chloride, glacial acetic acid, sodium acetate trihydrate and water for injections.See package 
leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
1 vial 
5 vials 
10vials 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
 
Read the package leaflet before use 
Intravenous use, for infusion after dilution 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 
 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 



   65 
 

 
 
This medicinal product does not require any special storage conditions prior to reconstitution. After 
dilution the infusion solution is stable for 24 hours at 2 °C - 8 °C (in a refrigerator) 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Pharmathen S.A. 
6, Dervenakion str. 
15351 Pallini, Attiki  
Greece 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/10/659/005 
EU/1/10/659/006 
EU/1/10/659/007     
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Iasibon 6 mg  

 
 

17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  



   66 
 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Iasibon 6 mg concentrate for solution for infusion  
ibandronic acid 
I.V. use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
Read the package leaflet before use 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6 ml 
 
 
6. OTHER 
 
 



   67 
 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Outer Carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Iasibon 50 mg film-coated tablets  
ibandronic acid 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 50 mg of ibandronic acid (as sodium monohydrate). 
 
 
3. LIST OF EXCIPIENTS 
 
The tablets also contain lactose. See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablets 
3 film-coated tablets 
6 film-coated tablets 
9 film-coated tablets 
28 film-coated tablets 
84 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Do not suck, chew or crush tablets 
Read the package leaflet before use 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 



   68 
 

Store in the original package in order to protect from moisture 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
 
Pharmathen S.A. 
6, Dervenakion str 
15351 Pallini, Attiki 
Greece   
Tel.: +302106604300 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
 
EU/1/10/659/001 
EU/1/10/659/002 
EU/1/10/659/008 
EU/1/10/659/009 
EU/1/10/659/0010    
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Iasibon 50 mg 

 
 

17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC:  
SN:  



   69 
 

NN:  



   70 
 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
Blister foil 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Iasibon 50 mg film-coated tablets 
ibandronic acid 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Pharmathen S.A 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
Mon 
Tue 
Wed 
Thu 
Fri 
Sat 
Sun 



   71 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



   72 
 

Package leaflet: Information for the patient 
 

Iasibon 1 mg concentrate for solution for infusion 
ibandronic acid 

 
Read all of this leaflet carefully before you start using this medicine because it contains important 
information for you. 
• Keep this leaflet. You may need to read it again. 
• If you have any further questions, ask your doctor, pharmacist or nurse. 
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4 
 

What is in this leaflet: 
1. What Iasibon is and what it is used for 
2. What you need to know before you receive Iasibon 
3. How to receive Iasibon 
4. Possible side effects 
5. How to store Iasibon 
6. Contents of the pack and other information 
 
 

1. What Iasibon is and what it is used for 
 
Iasibon contains the active substance ibandronic acid. This belongs to a group of medicines called 
bisphosphonates. 
  
Iasibon is used in adults and prescribed to you if you have breast cancer that has spread to your bones 
(called ‘bone metastases’).  
• It helps to prevent your bones from breaking (fractures) 
• It helps to prevent other bone problems that may need surgery or radiotherapy  
 
Iasibon can also be prescribed if you have a raised calcium level in your blood due to a tumour. 
 
Iasibon works by reducing the amount of calcium that is lost from your bones. This helps to stop your 
bones from getting weaker.  
 
 

2. What you need to know before you receive Iasibon  
 
Do not receive Iasibon 
• if you are allergic  to ibandronic acid or any of the other ingredients of this medicine that are 

listed in section 6 
• if you have, or have ever had low levels of calcium in your blood. 
 
Do not receive this medicine if any of the above apply to you. If you are not sure, talk to your doctor or 
pharmacist before having Iasibon. 
 
Warnings and precautions 
Talk to your doctor, pharmacist or nurse before receiving Iasibon: 
• if you are allergic  to any other bisphosphonates 
• if you have high or low levels of vitamin D, calcium or any other minerals 
• if you have kidney problems 
• if you have heart problems and the doctor recommended to limit your daily fluid intake 
• if you are having dental treatment or surgery or know that you need some in the future, tell your 

dentist that you are being treated with Iasibon for cancer 
 



   73 
 

Cases of serious, sometimes fatal allergic reaction have been reported in patients treated with 
intravenous ibandronic acid. 
If you experience one of the following symptoms, such as shortness of breath/difficulty breathing, tight 
feeling in throat, swelling of tongue, dizziness, feeling of loss of consciousness, redness or swelling of 
face, body rash, nausea and vomiting, you should immediately alert your doctor or nurse (see section 4). 
 
Children and adolescents 
Iasibon should not be used in children and adolescents below the age of 18 years. 
 
Other medicines and Iasibon 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. 
This is because Iasibon can affect the way some other medicines work. Also, some other medicines can 
affect the way Iasibon works. 
 
In particular, tell your doctor or pharmacist if you are receiving a type of antibiotic injection called 
‘aminoglycoside’ such as gentamicin. This is because aminoglycosides and Iasibon can both lower the 
amount of calcium in your blood.  
 
Pregnancy and breast-feeding 
Do not receive Iasibon if you are pregnant, planning to get pregnant or if you are breast-feeding. Ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Driving and using machines 
You can drive and use machines as it’s expected that Iasibon affectshas no or negligible effect on your 
ability to drive and use machines. Talk to your doctor first if you want to drive, use machines or tools.  
 
Iasibon contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium-free”. 
 
 
3. How to receive Iasibon 
 
Receiving this medicine 
• Iasibon is normally given by a doctor or other medical staff who have experience with the 
treatment of cancer. 
• it is given as an infusion into your vein 
 
Your doctor may do regular blood tests while you are receiving Iasibon. This is to check that you are 
being given the right amount of this medicine.  
 
How much to receive 
Your doctor will work out how much Iasibon you will be given depending on your illness.  
If you have breast cancer that has spread to your bones, then the recommended dose is 6 ampoules 
(6 mg) every 3-4 weeks, as an infusion in your vein over at least 15 minutes. 
 
If you have a raised calcium level in your blood due to a tumour then the recommended dose is a single 
administration of 2 ampoules (2 mg) or 4 ampoules (4 mg), depending on the severity of your illness. 
The medicine should be administered as an infusion in your vein over two hours. A repeated dose may 
be considered in case of insufficient response or if your illness reappears. 
Your doctor may adjust your dose and duration of intravenous infusion if you have kidney problems. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects although not everybody gets them. 
 



   74 
 

Talk to a nurse or a doctor straight away if you notice any of the following serious side effects - 
you may need urgent medical treatment: 
 
Rare (may affect up to 1 in 1,000 people) 
• persistent eye pain and inflammation 
• new pain, weakness or discomfort in your thigh, hip or groin. You may have early signs of a 

possible unusual fracture of the thigh bone. 
 
Very rare (may affect up to 1 in 10,000 people) 
• pain or sore in your mouth or jaw, You  may have  early signs of severe jaw problems (necrosis 

(dead bone tissue) in the jaw bone. 
• itching, swelling of your face, lips, tongue and throat, with difficulty breathing. You may be 

 having a serious, potentially life threatening allergic reaction (see section 2). 
• severe adverse skin reactions 
• ear pain, discharge from the ear, and/or an ear infection. These could be signs of bone damage in 

the ear.  
 

Not known (frequency cannot be estimated from the available data) 
• asthma attack 
 
Other possible side effects 
 
Common (may affect up to 1in 10 people) 
• rise in body temperature.  
• flu-like symptoms, including fever, shaking and shivering, feeling of discomfort, fatigue, bone 

pain and aching muscles and joints. These symptoms usually disappear within a couple of hours 
or days. Talk to a nurse or doctor if any effects become troublesome or last more than a couple of 
days 

• stomach and tummy pain, indigestion, being sick vomiting or having diarrhoea (loose bowels) 
• low calcium or phosphate levels in your blood 
• changes in blood test results such as Gamma GT or creatinine  
• a heart rhythm problem called ‘bundle branch block’ 
• pain in your bone or muscles  
• headache, feeling dizzy or feeling weak 
• feeling thirsty, sore throat, changes in taste 
• swollen legs or feet 
• aching joints, arthritis, or other joint problems 
• problems with your parathyroid gland 
• bruising 
• infections  
• a problem with your eyes called ‘cataracts’  
• skin problems 
• tooth problems.  
 
Uncommon (may affect less than 1 in 100 people)  
• shaking or shivering  
• your body temperature getting too low (‘hypothermia’) 
• a condition affecting the blood vessels in your brain called ‘cerebrovascular disorder’ (stroke  
 or brain bleeding) 
• heart and circulatory problems (including palpitations, heart attack, hypertension (high blood 

pressure) and varicose veins)  
• changes in your blood cells (‘anaemia’) 
• a high level of alkaline phosphatase in your blood 
• fluid build up and swelling (‘lymphoedema’) 
• fluid in your lungs 



   75 
 

• stomach problems such as ‘gastroenteritis’ or ‘gastritis’ 
• gallstones  
• being unable to pass water (urine), cystitis (bladder inflammation) 
• migraine 
• pain in your nerves, damaged nerve root  
• deafness  
• increased sensitivity of sound, taste or touch or changes in smell 
• difficulty swallowing 
• mouth ulcers, swollen lips (‘cheilitis’), oral thrush  
• itching or tingling skin around your mouth 
• pelvic pain, discharge, itching or pain in the vagina 
• a skin growth called a ‘benign skin neoplasm’ 
• memory loss  
• sleep problems, feeling anxious, emotional instability, or mood swings  
• skin rash  
• hair loss 
• injury or pain at the injection site 
• weight loss   
• kidney cyst (fluid-filled sac in the kidney) 
 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet.You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Iasibon 
 
• Keep this medicine out of the sight and reach of children. 
• Do not use this medicine after the expiry date which is stated on the folding box and on the label 

after EXP. The expiry date refers to the last day of that month 
• After dilution the infusion solution is stable for 24 hours at 2-8 °C (in a refrigerator) 
• Do not use this medicine if you notice that the solution is not clear or contains particles 
 
 
6. Content of the pack and other information 
 
What Iasibon contains 
• The active substance is ibandronic acid. One ampoule with 1 ml of a concentrate for solution for 

infusion contains 1 mg ibandronic acid (as sodium monohydrate) 
• The other ingredients are sodium chloride, glacial acetic acid, sodium acetate trihydrate and water 

for injections 
 
What Iasibon looks like and contents of the pack 
Iasibon is a colourless, clear solution. Iasibon 1 mg is supplied as pack containing 1 ampoule (2 ml type 
I glass ampoule).  
 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing Authorisation Holder 
Pharmathen S.A. 
Dervenakion 6  

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


   76 
 

Pallini 15351 
Attiki  
Greece 
 
Manufacturer 
Pharmathen S.A. 
Dervenakion 6  
Pallini 15351 
Attiki  
Greece 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder. 
 
België/Belgique/Belgien 
Pharmathen S.A. 
Tél/Tel: +30 210 66 04 300 
 

Lietuva 
SIA ELVIM 
Tel: +371 67808450 
 

България  
Alvogen Pharma Bulgaria Ltd 
Teл.: + 359 2  441 7136 
 

Luxembourg/Luxemburg 
Pharmathen S.A. 
Tél/Tel: +30 210 66 04 300 
 

Česká republika 
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Magyarország  
Pharmathen S.A. 
Tel.: +30 210 66 04 300 
 

Danmark 
Pharmathen S.A. 
Tlf: +30 210 66 04 300 
 

Malta 
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Deutschland 
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Nederland 
Glenmark Generics B.V.   
Tel: 0031 20 5226030 
 

Eesti (Estonia) 
SIA ELVIM 
Tel: +371 67808450 
 

Norge 
Pharmathen S.A. 
Tlf: +30 210 66 04 300 
 

Ελλάδα 
INNOVIS PHARMA AEBE  
Τηλ: +30 210 6664805-806 
 

Österreich  
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

España 
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Polska 
Pharmathen S.A. 
Tel.: +30 210 66 04 300 
 

France 
Pharmathen S.A. 
Tél: +30 210 66 04 300 
 

Portugal 
Pharmathen S.A. 
Tel: +30 210 66 04 300 

Hrvatska 
Pharmathen S.A. 
Tel: +30 210 66 04 300 

România 
Alvogen Romania SRL  
Tel: +(40) 21 351 0286 
 

Ireland 
Pharmathen S.A. 
Tel: +30 210 66 04 300 

Slovenija 
Pharmathen S.A. 
Tel: +30 210 66 04 300 



   77 
 

 
Ísland 
Alvogen ehf. 
Sími: +354 522 2900 

Slovenská republika  
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Italia 
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Suomi/Finland 
Pharmathen S.A. 
Puh/Tel: +30 210 66 04 300 

Κύπρος 
The Star Medicines Importers Co. Ltd 
Τηλ: +357 25371056 

Sverige  
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Latvija  
SIA ELVIM 
Tel: +371 67808450 
 

United Kingdom 
Aspire Pharma Ltd 
Tel: +44 1730 231148 
 

 
 
This leaflet was last revised in  
 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/. 
 
--------------------------------------------------------------------------------------------------------------------- 
The following information is intended for healthcare professionals only 
 
Dose: Prevention of skeletal events in patients with breast cancer and bone metastases 
The recommended dose for prevention of skeletal events in patients with breast cancer and bone 
metastases is 6 mg intravenously given every 3-4 weeks. The dose should be infused over at least 15 
minutes.  
 
Patients with renal impairment  
For patients with mild renal impairment (CLcr ≥50 and <80 mL/min) no dosage adjustment is 
necessary. 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: 
 

Creatinine Clearance 
(ml/min) Dosage Infusion Volume 

1 and Time 2 

≥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. 
 
Dose: Treatment of tumour-induced hypercalcaemia 
Iasibon is usually administered in a hospital setting. The dose is determined by the doctor considering 
the following factors. 
 

http://www.ema.europa.eu/


   78 
 

Prior to treatment with Iasibon the patient should be adequately rehydrated with 9 mg/ml (0.9%) sodium 
chloride. Consideration should be given to the severity of the hypercalcaemia as well as the tumour 
type. In most patients with severe hypercalcaemia (albumin-corrected serum calcium* ≥3 mmol/l or 
≥12 mg/dl) 4 mg is an adequate single dosage. In patients with moderate hypercalcaemia (albumin-
corrected serum calcium <3 mmol/l or <12 mg/dl) 2 mg is an effective dose. The highest dose used in 
clinical trials was 6 mg but this dose does not add any further benefit in terms of efficacy. 
 
* Note albumin-corrected serum calcium concentrations are calculated as follows: 
 
Albumin-corrected  
Serum calcium  
(mmol/l) 

= Serum calcium (mmol/l) - [0.02 x albumin (g/l)] + 0.8 

or 
Albumin-corrected  
Serum calcium (mg/dl) 

= Serum calcium (mg/dl) + 0.8 x [4 - albumin (g/dl)] 

   
To convert the albumin-corrected serum calcium in mmol/l value to mg/dl, multiply by 4. 
 
In most cases a raised serum calcium level can be reduced to the normal range within 7 days. The 
median time to relapse (re-increase of serum albumin-corrected serum calcium above 3 mmol/l) was 18-
19 days for the 2 mg and 4 mg doses. The median time to relapse was 26 days with a dose of 6 mg. 
 
Method and route of administration 
Iasibon concentrate for solution for infusion should be administered as an intravenous infusion. 
 
For this purpose the contents of the vial are to be used as follows: 
• Prevention of Skeletal Events in patients with breast cancer and bone metastases - added to 100 ml 

isotonic sodium chloride solution or 100 ml 5% dextrose solution and infused over at least 15 
minutes. See also dosage section above for patients with renal impairment 

• Treatment of tumour-induced hypercalcaemia - added to 500 ml isotonic sodium chloride solution 
or 500 ml 5% dextrose solution and infused over 2 hours 

 
Note: 
In order to avoid potential incompatibilities Iasibon concentrate for solution for infusion should only be 
diluted with isotonic sodium chloride solution or 5% dextrose solution. Calcium containing solutions 
should not be mixed with Iasibon concentrate for solution for infusion. 
 
Diluted solutions are for single use. Only clear solutions without particles should be used. 
 
 
It is recommended that the product once diluted be used immediately (see point 5 of this leaflet “How to 
store Iasibon”). 
 
Iasibon concentrate for solution for infusion should be administered as an intravenous infusion.  
Care must be taken not to  administer Iasibon concentrate for solution for infusion via intra-arterial or 
paravenous administration, as this could lead to tissue damage.. 
 
Frequency of administration 
For treatment of tumour induced hypercalcaemia, Iasibon concentrate for solution for infusion is 
generally given as a single infusion.  
 
For the prevention of skeletal events in patients with breast cancer and bone metastases, the Iasibon 
infusion is repeated at 3-4 week intervals.  
 
Duration of treatment 
A limited number of patients (50 patients) have received a second infusion for hypercalcaemia. 
Repeated treatment may be considered in case of recurrent hypercalcaemia or insufficient efficacy. 



   79 
 

 
For patients with breast cancer and bone metastases, Iasibon infusion should be administered every 3-4 
weeks. In clinical trials, therapy has continued for up to 96 weeks. 
 
Overdose 
Up to now there is no experience of acute poisoning with Iasibon concentrate for solution for infusion. 
Since both the kidney and the liver were found to be target organs for toxicity in preclinical studies with 
high doses, kidney and liver function should be monitored. 
 
Clinically relevant hypocalcaemia (very low serum calcium levels) should be corrected by intravenous 
administration of calcium gluconate. 



   80 
 

Package leaflet: Information for the patient 
 

Iasibon 2 mg concentrate for solution for infusion  
ibandronic acid 

 
Read all of this leaflet carefully before you start using this medicine because it contains important 
information for you. 
• Keep this leaflet. You may need to read it again. 
• If you have any further questions, ask your doctor, pharmacist or nurse 
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4 
 
What is in this leaflet: 
1. What Iasibon is and what it is used for 
2. What you need to know before you receive Iasibon 
3. How to receive Iasibon 
4. Possible side effects 
5. How to store Iasibon 
6. Contents of the pack and other information 
 
 
1. What Iasibon is and what it is used for 
 
Iasibon contains the active substance ibandronic acid. This belongs to a group of medicines called 
bisphosphonates. 
 
Iasibon is used in adults and prescribed to you if you have breast cancer that has spread to your bones 
(called ‘bone metastases’).  
• It helps to prevent your bones from breaking (fractures) 
• It helps to prevent other bone problems that may need surgery or radiotherapy   
 
Iasibon can also be prescribed if you have a raised calcium level in your blood due to a tumour. 
 
Iasibon works by reducing the amount of calcium that is lost from your bones. This helps to stop your 
bones from getting weaker.  
 
 
2. What you need to know before you receive Iasibon 
 
Do not receive Iasibon 
• if you are allergic to ibandronic acid or any of the other ingredients of 

this medicine that are listed in section 6 
• if you have, or have ever had low levels of calcium in your blood 

 
Do not receive this medicine if any of the above apply to you. If you are not sure, talk to your doctor or 
pharmacist before having Iasibon. 
 
Warnings and precautions 
Talk to your doctor, pharmacist or nurse before receiving Iasibon: 
• if you are allergic  to any other bisphosphonates 
• if you have high or low levels of vitamin D calcium or any other minerals 
• if you have kidney problems. 
• if you have heart problems and the doctor recommended to limit your daily fluid intake 
• if you are having dental treatment or surgery or know that you need some in the future, tell your 

dentist that you are being treated with Iasibon for cancer 
 



   81 
 

Cases of serious, sometimes fatal allergic reaction have been reported in patients treated with 
intravenous ibandronic acid. 
If you experience one of the following symptoms, such as shortness of breath/difficulty breathing, tight 
feeling in throat, swelling of tongue, dizziness, feeling of loss of consciousness, redness or swelling of 
face, body rash, nausea and vomiting, you should immediately alert your doctor or nurse (see section 4). 
 
Children and adolescents 
Iasibon should not be used in children and adolescents below the age of 18 years. 
 
Othermedicines and Iasibon 
Tell your doctor or pharmacist if you are taking,  have recently taken or might take any other medicines. 
This is because Iasibon can affect the way some other medicines work. Also, some other medicines can 
affect the way Iasibon works. 
 
In particular, tell your doctor or pharmacist if you are receiving a type of antibiotic injection called 
‘aminoglycoside’ such as gentamicin. This is because aminoglycosides and Iasibon can both lower the 
amount of calcium in your blood.  
 
Pregnancy and breast-feeding 
Do not receive Iasibon if you are pregnant, planning to get pregnant or if you are breast-feeding. Ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Driving and using machines 
You can drive and use machines as it’s expected that Iasibon has no or negligible effect on your ability 
to drive and use machines. Talk to your doctor first if you want to drive, use machines or tools.  
 
Iasibon contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium-free”. 
 
 
3. How to receive Iasibon 
 
Receiving this medicine 
• Iasibon is normally given by a doctor or other medical staff who have experience with the 
treatment of cancer. 
• it is given as an infusion into your vein 
 
Your doctor may do regular blood tests while you are receiving Iasibon. This is to check that you are 
being given the right amount of this medicine.  
 
How much to receive 
Your doctor will work out how much Iasibon you will be given depending on your illness.  
If you have breast cancer that has spread to your bones, then the recommended dose is 3 ampoules 
(6 mg) every 3-4 weeks, as an infusion in your vein over at least 15 minutes. 
 
If you have a raised calcium level in your blood due to a tumour then the recommended dose is a single 
administration of 1 ampoule (2 mg) or 2 ampoules (4 mg), depending on the severity of your illness. 
The medicine should be administered as an infusion in your vein over two hours. A repeated dose may 
be considered in case of insufficient response or if your illness reappears. 
Your doctor may adjust your dose and duration of intravenous infusion if you have kidney problems. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects although not everybody gets them. 
 



   82 
 

Talk to a nurse or a doctor straight away if you notice any of the following serious side effects - 
you may need urgent medical treatment: 
 
Rare (may affect up to 1 in 1,000 people) 
• persistent eye pain and inflammation 
• new pain, weakness or discomfort in your thigh, hip or groin. You may have early signs of a 

possible unusual fracture of the thigh bone. 
 

Very rare (may affect up to 1 in 10,000 people) 
• pain or sore in your mouth or jaw You  may have  early signs of severe jaw problems (necrosis 

(dead bone tissue) in the jaw bone). 
• itching, swelling of your face, lips, tongue and throat, with difficulty breathing. You may be 

 having a serious, potentially life threatening allergic reaction  (see section 2) 
• severe adverse skin reactions 
• ear pain, discharge from the ear, and/or an ear infection. These could be signs of bone damage in 

the ear.  
 
Not known (frequency cannot be estimated from the available data) 
• asthma attack 
 
Other possible side effects 
 
 
Common (may affect up to 1 in 10 people) 
• flu-like symptoms, including fever, shaking and shivering, feeling of discomfort, fatigue, bone 

pain and aching muscles and joints. These symptoms usually disappear within a couple of hours 
or days. Talk to a nurse or doctor if any effects become troublesome or last more than a couple of 
days 

• rise in body temperature.  
• stomach and tummy pain, indigestion, being sick vomiting or having diarrhoea (loose bowels) 
• low calcium or phosphate levels in your blood 
• changes in blood test results such as Gamma GT or creatinine  
• a heart rhythm problem called ‘bundle branch block’ 
• pain in your bone or muscles  
• headache, feeling dizzy or feeling weak 
• feeling thirsty, sore throat, changes in taste 
• swollen legs or feet 
• aching joints, arthritis, or other joint problems 
• problems with your parathyroid gland 
• bruising 
• infections  
• a problem with your eyes called ‘cataracts’  
• skin problems 
• tooth problems.  
 
Uncommon (may affect less than 1 in 100 people) 
• shaking or shivering  
• your body temperature getting too low (‘hypothermia’) 
• a condition affecting the blood vessels in your brain called ‘cerebrovascular disorder’ (stroke  
 or brain bleeding)   
• heart and circulatory problems (including palpitations, heart attack, hypertension (high blood 

pressure) and varicose  veins)  
• changes in your blood cells (‘anaemia’) 
• a high level of alkaline phosphatase in your blood 
• fluid build up and swelling (‘lymphoedema’) 



   83 
 

• fluid in your lungs 
• stomach problems such as ‘gastroenteritis’ or ‘gastritis’ 
• gallstones  
•  being unable to pass water (urine), cystitis (bladder inflammation) 
• migraine 
• pain in your nerves, damaged nerve root  
• deafness  
• increased sensitivity of sound, taste or touch or changes in smell 
• difficulty swallowing 
• mouth ulcers, swollen lips (‘cheilitis’), oral thrush   
• itching or tingling skin around your mouth 
• pelvic pain, discharge, itching or pain in the vagina 
• a skin growth called a ‘benign skin neoplasm’ 
• memory loss  
• sleep problems, feeling anxious, emotional instability, or mood swings  
• skin rash 
• hair loss 
• injury or pain at the injection site 
• weight loss   
• kidney cyst (fluid-filled sac in the kidney) 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet.You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Iasibon 
 
• Keep this medicine out of the sightand reachof children. 
• Do not use this medicine after the expiry date which is stated on the folding box and on the label 

after EXP. The expiry date refers to the last day of that month. 
• After dilution the infusion solution is stable for 24 hours at 2-8 °C (in a refrigerator). 
• Do not use this medicine if you notice that the solution is not clear or contains particles. 
 
 
6. Content of the pack and other information  
 
What Iasibon contains 
• The active substance is ibandronic acid. One ampoule with 2 ml of a concentrate for solution for 

infusion contains2 mg ibandronic acid (as sodium monohydrate) 
• The other ingredients are sodium chloride, glacial acetic acid, sodium acetate trihydrate and water 

for injections 
 
What Iasibon looks like and contents of the pack 
Iasibon is a colourless, clear solution. Iasibon 2mg is supplied as pack containing 1 ampoule (4 ml type 
I glass ampoule).  
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing Authorisation Holder 
Pharmathen S.A. 
Dervenakion 6  
Pallini 15351 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


   84 
 

Attiki  
Greece 
 
Manufacturer  
Pharmathen S.A. 
Dervenakion 6  
Pallini 15351 
Attiki  
Greece 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder. 
 
België/Belgique/Belgien 
Pharmathen S.A. 
Tél/Tel: +30 210 66 04 300 
 

Lietuva 
SIA ELVIM 
Tel: +371 67808450 
 

България  
Alvogen Pharma Bulgaria Ltd 
Teл.: + 359 2  441 7136 
 

Luxembourg/Luxemburg 
Pharmathen S.A. 
Tél/Tel: +30 210 66 04 300 
 

Česká republika 
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Magyarország  
Pharmathen S.A. 
Tel.: +30 210 66 04 300 
 

Danmark 
Pharmathen S.A. 
Tlf: +30 210 66 04 300 
 

Malta 
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Deutschland 
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Nederland 
Glenmark Generics B.V.   
Tel: 0031 20 5226030 
 

Eesti (Estonia) 
SIA ELVIM 
Tel: +371 67808450 
 

Norge 
Pharmathen S.A. 
Tlf: +30 210 66 04 300 
 

Ελλάδα 
INNOVIS PHARMA AEBE  
Τηλ: +30 210 6664805-806 
 

Österreich  
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

España 
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Polska 
Pharmathen S.A. 
Tel.: +30 210 66 04 300 
 

France 
Pharmathen S.A. 
Tél: +30 210 66 04 300 
 

Portugal 
Pharmathen S.A. 
Tel: +30 210 66 04 300 

Hrvatska 
Pharmathen S.A. 
Tel: +30 210 66 04 300 

România 
Alvogen Romania SRL  
Tel: +(40) 21 351 0286 
 

Ireland 
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Slovenija 
Pharmathen S.A. 
Tel: +30 210 66 04 300 



   85 
 

Ísland 
Alvogen ehf. 
Sími: +354 522 2900 
 

Slovenská republika  
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Italia 
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Suomi/Finland 
Pharmathen S.A. 
Puh/Tel: +30 210 66 04 300 

Κύπρος 
The Star Medicines Importers Co. Ltd 
Τηλ: +357 25371056 

Sverige  
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Latvija  
SIA ELVIM 
Tel: +371 67808450 
 

United Kingdom 
Aspire Pharma Ltd 
Tel: +44 1730 231148 
 

 
This leaflet was last revised in {MM/YYYY} 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
------------------------------------------------------------------------------------------------------------------------- 
The following information is intended for healthcare professionals only 
 
Dose: Prevention of skeletal events in patients with breast cancer and bone metastases 
The recommended dose for prevention of skeletal events in patients with breast cancer and bone 
metastases is 6 mg intravenously given every 3-4 weeks. The dose should be infused over at least 15 
minutes.  
 
Patients with renal impairment  
For patients with mild renal impairment (CLcr ≥50 and <80 mL/min) no dosage adjustment is 
necessary. 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: 
 

Creatinine Clearance 
(ml/min) Dosage Infusion Volume 

1 and Time 2 

≥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. 
 
Dose: Treatment of tumour-induced hypercalcaemia 
Iasibon is usually administered in a hospital setting. The dose is determined by the doctor considering 
the following factors. 
 
Prior to treatment with Iasibon the patient should be adequately rehydrated with 9 mg/ml (0.9%) sodium 
chloride. Consideration should be given to the severity of the hypercalcaemia as well as the tumour 
type. In most patients with severe hypercalcaemia (albumin-corrected serum calcium* ≥3 mmol/l or 

http://www.ema.europa.eu/


   86 
 

≥12 mg/dl) 4 mg is an adequate single dosage. In patients with moderate hypercalcaemia (albumin-
corrected serum calcium <3 mmol/l or <12 mg/dl) 2 mg is an effective dose. The highest dose used in 
clinical trials was 6 mg but this dose does not add any further benefit in terms of efficacy. 
 
* Note albumin-corrected serum calcium concentrations are calculated as follows: 
 
Albumin-corrected  
Serum calcium  
(mmol/l) 

= Serum calcium (mmol/l) - [0.02 x albumin (g/l)] + 0.8 

or 
Albumin-corrected  
Serum calcium (mg/dl) 

= Serum calcium (mg/dl) + 0.8 x [4 - albumin (g/dl)] 

   
To convert the albumin-corrected serum calcium in mmol/l value to mg/dl, multiply by 4. 
 
In most cases a raised serum calcium level can be reduced to the normal range within 7 days. The 
median time to relapse (re-increase of serum albumin-corrected serum calcium above 3 mmol/l) was 18-
19 days for the 2 mg and 4 mg doses. The median time to relapse was 26 days with a dose of 6 mg. 
 
Method and route of administration 
Iasibon concentrate for solution for infusion should be administered as an intravenous infusion. 
 
For this purpose the contents of the vial are to be used as follows: 
• Prevention of Skeletal Events in patients with breast cancer and bone metastases - added to 100 ml 

isotonic sodium chloride solution or 100 ml 5% dextrose solution and infused over at least 15 
minutes. See also dosage section above for patients with renal impairment 

• Treatment of tumour-induced hypercalcaemia - added to 500 ml isotonic sodium chloride solution 
or 500 ml 5% dextrose solution and infused over 2 hours 

 
Note: 
In order to avoid potential incompatibilities Iasibon concentrate for solution for infusion should only be 
diluted with isotonic sodium chloride solution or 5% dextrose solution. Calcium containing solutions 
should not be mixed with Iasibon concentrate for solution for infusion. 
 
Diluted solutions are for single use. Only clear solutions without particles should be used. 
 
 
It is recommended that the product once diluted be used immediately (see point 5 of this leaflet “How to 
store Iasibon”). 
 
Iasibon concentrate for solution for infusion should be administered as an intravenous infusion.  
Care must be taken to e administer Iasibon concentrate for solution for infusion via intra-arterial or 
paravenous administration, as this could lead to tissue damage. 
 
Frequency of administration 
For treatment of tumour induced hypercalcaemia, Iasibon concentrate for solution for infusion is 
generally given as a single infusion.  
 
For the prevention of skeletal events in patients with breast cancer and bone metastases, the Iasibon 
infusion is repeated at 3-4 week intervals.  
Duration of treatment 
A limited number of patients (50 patients) have received a second infusion for hypercalcaemia. 
Repeated treatment may be considered in case of recurrent hypercalcaemia or insufficient efficacy. 
 
For patients with breast cancer and bone metastases, Iasibon infusion should be administered every 3-4 
weeks. In clinical trials, therapy has continued for up to 96 weeks. 
 



   87 
 

Overdose 
Up to now there is no experience of acute poisoning with Iasibon concentrate for solution for infusion. 
Since both the kidney and the liver were found to be target organs for toxicity in preclinical studies with 
high doses, kidney and liver function should be monitored. 
 
Clinically relevant hypocalcaemia (very low serum calcium levels) should be corrected by intravenous 
administration of calcium gluconate. 



   88 
 

Package leaflet: Information for the patient 
 

Iasibon 6 mg concentrate for solution for infusion  
ibandronic acid 

 
Read all of this leaflet carefully before you start using this medicine because it contains important 
information for you. 
• Keep this leaflet. You may need to read it again. 
• If you have any further questions, ask your doctor, pharmacist or nurse 
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet: 
1. What Iasibon is and what it is used for 
2. What you need to know before you receive Iasibon 
3. How to receive Iasibon 
4. Possible side effects 
5. How to store Iasibon 
6. Contents of the pack and other information 
 
 
1. What Iasibon is and what it is used for 
 
Iasibon contains the active substance ibandronic acid. This belongs to a group of medicines called 
bisphosphonates. 

 
Iasibon is used in adults and prescribed to you if you have breast cancer that has spread to your bones 
(called ‘bone metastases’)  
• It helps to prevent your bones from breaking (fractures) 
• It helps to prevent other bone problems that may need surgery or radiotherapy  

 
Iasibon can also be prescribed if you have a raised calcium level in your blood due to a tumour. 

 
Iasibon works by reducing the amount of calcium that is lost from your bones. This helps to stop your 
bones from getting weaker.  
 
 
2. What you need to know before you receive Iasibon 
 
Do not receive Iasibon 
• if you are allergic to ibandronic acid or any of the other ingredients of this medicine that are listed 

in section 6 
• if you have low calcium levels in your blood (hypocalcaemia). 
Do not receive this medicine if any of the above apply to you. If you are not sure, talk to your doctor or 
pharmacist before having Iasibon. 

Warnings and precautions 
Talk to your doctor, pharmacist or nurse before receiving Iasibon: 
• if you are allergic to any other bisphosphonates 
• if you have high or low levels of vitamin D, calcium or any other minerals 
• if you have kidney problems. 
• If you have heart problems and the doctor recommended to limit your daily fluid intake 
• If you are having dental treatment or surgery or know that you need some in the future, tell your 

dentist that you are being treated with Iasibon for cancer 
 
Cases of serious, sometimes fatal allergic reaction have been reported in patients treated with 



   89 
 

intravenous ibandronic acid. 
If you experience one of the following symptoms, such as shortness of breath/difficulty breathing, tight 
feeling in throat, swelling of tongue, dizziness, feeling of loss of consciousness, redness or swelling of 
face, body rash, nausea and vomiting, you should immediately alert your doctor or nurse (see section 4). 
 
Children and adolescents 
Iasibon should not be used in children and adolescentsbelow the age of 18 years. 
 
Other medicines and Iasibon 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. 
This is because Iasibon can affect the way some other medicines work. Also, some other medicines can 
affect the way Iasibon works. 
 
In particular, tell your doctor or pharmacist if you are receiving a type of antibiotic injection called 
‘aminoglycoside’ such as gentamicin. This is because aminoglycosides and Iasibon can both lower the 
amount of calcium in your blood.  
 
Pregnancy and breast-feeding 
Do not receive Iasibon if you are pregnant, planning to get pregnant or if you are breast-feeding. Ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Driving and using machines: 
You can drive and use machines as it’s expected that Iasibon has no or negligible effect on your ability 
to drive and use machines. Talk to your doctor first if you want to drive, use machines or tools.  
 
Iasibon contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium-free”. 
 
 
3. How to receive Iasibon 
 
Receiving this medicine 
• Iasibon is normally given by a doctor or other medical staff who have experience with the 
treatment of cancer. 
• It is given as an infusion into your vein 
 
Your doctor may do regular blood tests while you are receiving Iasibon. This is to check that you are 
being given the right amount of this medicine.  
 
How much to receive 
Your doctor will work out how much Iasibon you will be given depending on your illness.  
If you have breast cancer that has spread to your bones, then the recommended dose is 1 vial (6 mg) 
every 3-4 weeks, as an infusion in your vein over at least 15 minutes. 
 
If you have a raised calcium level in your blood due to a tumour, then the recommended dose is a single 
administration of 2 mg or 4 mg, depending on the severity of your illness. The medicine should be 
administered as an infusion in your vein over two hours. A repeated dose may be considered in case of 
insufficient response or if your illness reappears. 
Your doctor may adjust your dose and duration of intravenous infusion if you have kidney problems. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Talk to a nurse or a doctor straight away if you notice any of the following serious side effects - 



   90 
 

you may need urgent medical treatment: 
 
Rare (may affect up to 1 in 1,000 people) 
• persistent eye pain and inflammation 
• new pain, weakness or discomfort in your thigh, hip or groin. You may have early signs of a 

possible unusual fracture of the thigh bone 
 
Very rare (may affect up to 1 in 10,000 people) 
• pain or sore in your mouth or jaw. You may have early signs of severe jaw problems (necrosis 

(dead bone tissue) in the jaw bone). 
• itching, swelling of your face, lips, tongue and throat, with difficulty breathing. You may be 

 having a serious, potentially life threatening allergic reaction  (see section 2) 
• severe adverse skin reactions 
• ear pain, discharge from the ear, and/or an ear infection. These could be signs of bone damage in 

the ear.  
 

Not known (frequency cannot be estimated from the available data) 
• asthma attack 
 
Other possible side effects 
 
 
Common (may affect up to 1 in 10 people) 
• flu-like symptoms, including fever, shaking and shivering, feeling of discomfort, fatigue, bone 

pain and aching muscles and joints. These symptoms usually disappear within a couple of hours 
or days. Talk to a nurse or doctor if any effects become troublesome or last more than a couple of 
days 

• rise in body temperature.  
• stomach and tummy pain, indigestion, being sick vomiting or having diarrhoea (loose bowels) 
• low calcium or phosphate levels in your blood 
• changes in blood test results such as Gamma GT or creatinine  
• a heart rhythm problem called ‘bundle branch block’ 
• pain in your bone or  muscles  
• headache, feeling dizzy or feeling weak 
• feeling thirsty, sore throat, changes in taste 
• swollen legs or feet 
• aching joints, arthritis, or other joint problems 
• problems with your parathyroid gland 
• bruising 
• infections  
• a problem with your eyes called ‘cataracts’  
• skin problems 
• tooth problems.  
 
Uncommon (may affect less than 1 in 100 people) 
• shaking or shivering  
• your body temperature getting too low (‘hypothermia’) 
• a condition affecting the blood vessels in your brain called ‘cerebrovascular disorder’ (stroke  

or brain bleeding) 
• heart and circulatory problems (including palpitations, heart attack, hypertension , high blood 

pressure and varicose veins)  
• changes in your blood cells (‘anaemia’) 
• a high level of alkaline phosphatase in your blood 
• fluid build up and swelling (‘lymphoedema’) 
• fluid in your lungs 



   91 
 

• stomach problems such as ‘gastroenteritis’ or ‘gastritis’ 
• gallstones  
•  being unable to pass water (urine), cystitis (bladder inflammation) 
• migraine 
• pain in your nerves, damaged nerve root  
• deafness  
• increased sensitivity of sound, taste or touch or changes in smell 
• difficulty swallowing 
• mouth ulcers, swollen lips (‘cheilitis’), oral thrush   
• itching or tingling skin around your mouth 
• pelvic pain, discharge, itching or pain in the vagina 
• a skin growth called a ‘benign skin neoplasm’ 
• memory loss  
• sleep problems, feeling anxious, emotional instability, or mood swings  
• skin rash 
• hair loss 
• injury or pain at the injection site 
• weight loss   
• kidney cyst (fluid-filled sac in the kidney). 
 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Iasibon 
 
• Keep this medicine out of the sightand reachof children 
• Do not use this medicine after the expiry date which is stated on the folding box and on the label 

after EXP. The expiry date refers to the last day of that month. 
• After dilution the infusion solution is stable for 24 hours at 2-8 °C (in a refrigerator) 
• Do not use this medicine if you notice that the solution is not clear or contains particles 
 
 
6. Content of the pack and other information 
 
What Iasibon contains 
• The active substance is ibandronic acid. One vial with 6 ml of a concentrate for solution for 

infusion contains 6 mg ibandronic acid (as sodium monohydrate). 
• The other ingredients are sodium chloride, glacial acetic acid, sodium acetate trihydrate and water 

for injections. 
 
What Iasibon looks like and contents of the pack 
Iasibon is a colourless, clear solution. Iasibon 6mg is supplied as packs containing 1, 5 and 10 vials (9 
ml type I glass vial with a bromobutyl rubber stopper).  
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing Authorisation Holder 
Pharmathen S.A. 
Dervenakion 6  

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


   92 
 

Pallini 15351 
Attiki  
Greece 
 
Manufacturer  
Pharmathen S.A. 
Dervenakion 6  
Pallini 15351 
Attiki  
Greece 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder. 
 
 
België/Belgique/Belgien 
Pharmathen S.A. 
Tél/Tel: +30 210 66 04 300 
 

Lietuva 
SIA ELVIM 
Tel: +371 67808450 
 

България  
Alvogen Pharma Bulgaria Ltd 
Teл.: + 359 2  441 7136 
 

Luxembourg/Luxemburg 
Pharmathen S.A. 
Tél/Tel: +30 210 66 04 300 
 

Česká republika 
PHARMAGEN CZ s.r.o. 
Tel: +420 721 137 749 
 

Magyarország  
Pharmathen S.A. 
Tel.: +30 210 66 04 300 
 

Danmark 
Pharmathen S.A. 
Tlf: +30 210 66 04 300 
 

Malta 
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Deutschland 
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Nederland 
Glenmark Generics B.V.   
Tel: 0031 20 5226030 
 

Eesti (Estonia) 
SIA ELVIM 
Tel: +371 67808450 
 

Norge 
Pharmathen S.A. 
Tlf: +30 210 66 04 300 
 

Ελλάδα 
INNOVIS PHARMA AEBE  
Τηλ: +30 210 6664805-806 
 

Österreich  
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

España 
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Polska 
Pharmathen S.A. 
Tel.: +30 210 66 04 300 
 

France 
Pharmathen S.A. 
Tél: +30 210 66 04 300 
 

Portugal 
Pharmathen S.A. 
Tel: +30 210 66 04 300 

Hrvatska 
Pharmathen S.A. 
Tel: +30 210 66 04 300 

România 
Alvogen Romania SRL  
Tel: +(40) 21 351 0286 
 

Ireland 
Pharmathen S.A. 

Slovenija 
Pharmathen S.A. 



   93 
 

Tel: +30 210 66 04 300 
 

Tel: +30 210 66 04 300 

Ísland 
Alvogen ehf. 
Sími: +354 522 2900 
 

Slovenská republika  
PHARMAGEN CZ s.r.o. 
Tel: +420 721 137 749 
 

Italia 
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Suomi/Finland 
Pharmathen S.A. 
Puh/Tel: +30 210 66 04 300 

Κύπρος 
The Star Medicines Importers Co. Ltd 
Τηλ: +357 25371056 

Sverige  
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Latvija  
SIA ELVIM 
Tel: +371 67808450 
 

United Kingdom 
Aspire Pharma Ltd 
Tel: +44 1730 231148 
 

 
This leaflet was last revised in {MM/YYYY} 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
------------------------------------------------------------------------------------------------------------------------- 
The following information is intended for healthcare professionals only 
 
Dose: Prevention of skeletal events in patients with breast cancer and bone metastases 
The recommended dose for prevention of skeletal events in patients with breast cancer and bone 
metastases is 6 mg intravenously given every 3-4 weeks. The dose should be infused over at least 15 
minutes.  
 
Patients with renal impairment  
For patients with mild renal impairment (CLcr ≥50 and <80 mL/min) no dosage adjustment is 
necessary. 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: 
 

   
   
   
   

Creatinine Clearance 
(ml/min) Dosage Infusion Volume 

1 and Time 2 

≥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. 
 
Dose: Treatment of tumour-induced hypercalcaemia 

http://www.ema.europa.eu/


   94 
 

Iasibon is usually administered in a hospital setting. The dose is determined by the doctor considering 
the following factors. 
 
Prior to treatment with Iasibon the patient should be adequately rehydrated with 9 mg/ml (0.9%) sodium 
chloride. Consideration should be given to the severity of the hypercalcaemia as well as the tumour 
type. In most patients with severe hypercalcaemia (albumin-corrected serum calcium* ≥3 mmol/l or 
≥12 mg/dl) 4 mg is an adequate single dosage. In patients with moderate hypercalcaemia (albumin-
corrected serum calcium <3 mmol/l or <12 mg/dl) 2 mg is an effective dose. The highest dose used in 
clinical trials was 6 mg but this dose does not add any further benefit in terms of efficacy. 
 
* Note albumin-corrected serum calcium concentrations are calculated as follows: 
 
Albumin-corrected  
Serum calcium  
(mmol/l) 

= Serum calcium (mmol/l) - [0.02 x albumin (g/l)] + 0.8 

or 
Albumin-corrected  
Serum calcium (mg/dl) 

= Serum calcium (mg/dl) + 0.8 x [4 - albumin (g/dl)] 

   
To convert the albumin-corrected serum calcium in mmol/l value to mg/dl, multiply by 4. 
 
In most cases a raised serum calcium level can be reduced to the normal range within 7 days. The 
median time to relapse (re-increase of serum albumin-corrected serum calcium above 3 mmol/l) was 18-
19 days for the 2 mg and 4 mg doses. The median time to relapse was 26 days with a dose of 6 mg. 
 
Method and route of administration 
Iasibon concentrate for solution for infusion should be administered as an intravenous infusion. 
 
For this purpose the contents of the vial are to be used as follows: 
• Prevention of Skeletal Events in patients with breast cancer and bone metastases - added to 100 ml 

isotonic sodium chloride solution or 100 ml 5% dextrose solution and infused over at least 15 
minutes. See also dosage section above for patients with renal impairment 

• Treatment of tumour-induced hypercalcaemia - added to 500 ml isotonic sodium chloride solution 
or 500 ml 5% dextrose solution and infused over 2 hours 

 
Note: 
In order to avoid potential incompatibilities Iasibon concentrate for solution for infusion should only be 
diluted with isotonic sodium chloride solution or 5% dextrose solution. Calcium containing solutions 
should not be mixed with Iasibon concentrate for solution for infusion. 
 
Diluted solutions are for single use. Only clear solutions without particles should be used. 
 
 
It is recommended that the product once diluted be used immediately (see point 5 of this leaflet ‘How to 
store Iasibon’). 
 
Iasibon concentrate for solution for infusion should be administered as an intravenous infusion.  
Care must be taken not to administer Iasibon concentrate for solution for infusion via intra-arterial or 
paravenous administration, as this could lead to tissue damage. 
 
Frequency of administration 
For treatment of tumour induced hypercalcaemia, Iasibon concentrate for solution for infusion is 
generally given as a single infusion.  
 
For the prevention of skeletal events in patients with breast cancer and bone metastases, the Iasibon 
infusion is repeated at 3-4 week intervals.  
Duration of treatment 



   95 
 

A limited number of patients (50 patients) have received a second infusion for hypercalcaemia. 
Repeated treatment may be considered in case of recurrent hypercalcaemia or insufficient efficacy. 
 
For patients with breast cancer and bone metastases, Iasibon infusion should be administered every 3-4 
weeks. In clinical trials, therapy has continued for up to 96 weeks. 
 
Overdose 
Up to now there is no experience of acute poisoning with Iasibon concentrate for solution for infusion. 
Since both the kidney and the liver were found to be target organs for toxicity in preclinical studies with 
high doses, kidney and liver function should be monitored. 
 
Clinically relevant hypocalcaemia (very low serum calcium levels) should be corrected by intravenous 
administration of calcium gluconate. 



   96 
 

Package leaflet: Information for the patient 
 

Iasibon 50 mg film-coated tablets  
ibandronic acid 

 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
• Keep this leaflet. You may need to read it again. 
• If you have any further questions, ask your doctor or pharmacist. 
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4 
 
What is in this leaflet: 
1. What Iasibon is and what it is used for. 
2. What you need to know before you take Iasibon. 
3. How to take Iasibon. 
4. Possible side effects. 
5. How to store Iasibon. 
6. Contents of the pack and other information 
 
 
1. What Iasibon is and what it is used for 
 
Iasibon contains the active substance ibandronic acid. This belongs to a group of medicines called 
bisphosphonates.  
 
Iasibon is used in adults and prescribed to you if you have breast cancer that has spread to your bones 
(called ‘bone metastases’).  
 
• It helps to prevent your bones from breaking (fractures).  
• It also helps to prevent other bone problems that may need surgery or radiotherapy.  
 
Ibandronate works by reducing the amount of calcium that is lost from your bones. This helps to stop 
your bones from getting weaker.  
 
 
2. What you need to know before you take Iasibon  
 
Do not take Iasibon 
- if you are allergic  to ibandronic acid or any of the other ingredients of this medicine that are 

listed in section 6 
- if you have problems with your food pipe /gullet (oesophagus) such as narrowing or difficulty 

swallowing 
- if you cannot stand or sit upright for at least one hour (60 minutes) at a time 
- if you have or ever had low calcium in your blood. 
 
Do not take this medicine if any of the above apply to you. If you are not sure, talk to your doctor or 
pharmacist before taking Iasibon. 
 
Warnings and precautions  
Talk to your doctor or pharmacist before taking Iasibon: 
• if you are allergic to any other bisphosphonates 
• if you have any swallowing or digestion problems 
• if you have high or low blood levels of vitamin D or any other minerals 



   97 
 

• if you have kidney problems 
• if you are having dental treatment or surgery or know that you need some in the future, tell your 

dentist that you are being treated with Iasibon for cancer 
 
Irritation, inflammation or ulceration of the gullet/food pipe (oesophagus) often with symptoms of 
severe pain in the chest, severe pain after swallowing food and/or drink, severe nausea, or vomiting may 
occur, especially if you do not drink a full glass of water and/or if you lie down within an hour of taking 
Iasibon. If you develop these symptoms, stop taking Iasibon and tell your doctor straight away (see 
sections 3 and 4). 
 
Children and adolescents 
Iasibon should not be used in children and adolescents below the age of 18 years. 
 
Other medicines and Iasibon 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. 
This is because Iasibon can affect the way some other medicines work. Also some other medicines can 
affect the way Iasibon works. 

In particular, tell your doctor or pharmacist if you are taking any of the following medicines: 
• supplements containing calcium, magnesium, iron or aluminium 
• acetylsalicylic acid and non-steroidal anti-inflammatory medicines called “NSAIDs”, such as, 

ibuprofen or naproxen. This is because NSAIDs and Iasibon can both irritate your stomach and 
gut 

• a type of antibiotic injection called “aminoglycoside” such as gentamicin. This is because 
aminoglycosides and Iasibon can both lower the amount of calcium in your blood 

 
Taking medicines that reduce stomach acid such as cimetidine and ranitidine, may slightly increase the 
effects of Iasibon. 
 
Iasibon with food and drink 
Do not take Iasibon with food or any other drinks except plain water as Iasibon is less effective if it is 
taken with food or drink (see section 3).  
 
Take Iasibon at least 6 hours after you had last had anything to eat, drink or any other medicines or 
supplements (e.g. products containing calcium (milk), aluminium, magnesium and iron) except water. 
After taking your tablet, wait at least 30 minutes. Then you can have your first food and drink, and take 
any medicines or supplements (see section 3). 
 
Pregnancy and breast feeding 
Do not take Iasibon if you are pregnant, planning to get pregnant or if you are breast-feeding. 
Ask your doctor or pharmacist for advice before taking this medicine. 
 
Driving and using machines 
You can drive and use machines as it’s expected that Iasibon has no or negligible effect on your ability 
to drive and use machines. Talk to your doctor first if you want to drive, use machine or tools. 



   98 
 

 
Iasibon contains lactose.  
If you have been told by your doctor that you cannot tolerate or digest some sugars (e.g. if you have a 
galactose intolerance, the Lapp lactase deficiency or have problems with glucose-galactose absorption), 
talk to your doctor before taking this medicine. 
 
 
3. How to take Iasibon 
 
Always take this medicine exactly as your doctor has told you. You should check with your doctor or 
pharmacist if you are not sure. 
Take your tablet at least 6 hours after you had last had anything to eat, drink or any other medicines or 
supplements except water. Water with a high concentration of calcium should not be used. If there is 
concern regarding potentially high levels of calcium in the tap water (hard water), it is advised to use 
bottled water with a low mineral content. 
 
Your doctor may do regular blood tests while you are taking Iasibon. This is to check that you are being 
given the right amount of medicine. 
 
Taking this medicine 
It is important that you take Iasibon at the right time and in the right way. This is because it can cause 
irritation, inflammation or ulcers in your food pipe/gullet (oesophagus).  
 
You can help stop this happening by doing the following: 
• Take your tablet as soon as you get up for the day before having your first food, drink, any 

medicine or supplements 
 
• Take your tablet with a full glass of water only (about 200 mL). Do not take your tablet with any 

drink other than water 
 
• Swallow the tablet whole. Do not chew, suck or crush the tablet. Do not let the tablet dissolve in 

your mouth 
 
• After taking your tablet, wait at least 30 minutes. Then you can have your first food and drink and  

and take any medicines or supplements 
 

• Stay upright (sitting or standing) position while taking your tablet and for the next hour (60 
minutes). Otherwise, some of the medicine could leak back into your food pipe/gullet 
(oesophagus) 

 
How much to take 
The usual dose of Iasibon is one tablet each day. If you have moderate kidney problems, your doctor 
may reduce your dose to one tablet every other day. If you have severe kidney problems, your doctor 
may reduce your dose to one tablet each week. 
 
If you take more Iasibon than you should 
If you take too many tablets talk to a doctor or go to hospital straight away. Drink a full glass of milk 
before you go. Do not make yourself sick. Do not lie down. 
 
If you forget to take Iasibon 
Do not take a double dose to make up for a forgotten dose. If you are taking a tablet each day, skip the 
missed dose completely. Then carry on as usual the next day. If you are taking a tablet every other day 
or once a week, ask your doctor or pharmacist for advice. 



   99 
 

 
If you stop taking Iasibon 
Keep taking Iasibon for as long as your doctor tells you. This is because the medicine will only work if 
it is taken all the time. 
 
If you have any further questions on the use of this medicines, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects although not everybody gets them. 
 
 
Talk to a nurse or a doctor straight away if you notice any of the following serious side effects, you 
may need urgent medical treatment: 
 
Common (may affect up to 1 in 10 people):  
• feeling sick, heartburn and discomfort in swallowing (inflammation of your gullet/ food pipe) 
 
Uncommon (may affect less than 1 in 100 people): 
• severe stomach pain. This could be a sign of an ulcer of the first section of the bowel (duodenum) 

that is bleeding, or that your stomach is inflamed (gastritis) 
 
Rare (may affect up to 1 in 1,000 people) 
• persistent eye pain and inflammation 
• new pain, weakness or discomfort in your thigh, hip or groin. You may have early signs of a 

possible unusual fracture of the thigh bone 
 
Very rare (may affect up to 1 in 10,000 people) 
• pain or sore in your mouth or jaw. You may have early signs of severe jaw problems (necrosis 

(dead bone tissue) in the jaw bone) 
• itching, swelling of your face, lips, tongue and throat, with difficulty breathing. You may be 

having a serious, potentially life threatening allergic reaction 
• severe adverse skin reactions 
• ear pain, discharge from the ear, and/or an ear infection. These could be signs of bone damage in 

the ear.  
 

Not known (frequency cannot be estimated from the available data) 
• asthma attack 
 
Other possible side effects 
 
Common (may affect up to 1 in 10 people):  
• tummy pain, indigestion 
• low calcium levels in your blood 
• weakness 
 
Uncommon (may affect less than 1 in 100 people): 
• chest pain 
• itching or tingling skin (paraesthesia) 
• flu-like symptoms, feeling generally unwell or in pain 
• dry mouth, strange taste in your mouth or difficulty swallowing 
• anaemia (bloodlessness) 
• high levels of urea or high levels of parathyroid hormone in your blood. 
 
 



   100 
 

Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V. By reporting side effects you can help provide more information on the safety of this 
medicine. 
 
 
5. How to store Iasibon  
 
• Keep this medicine out of the sightand reachof children 
• Do not use this medicine after the expiry date which is stated on the blister and carton after EXP. 

The expiry date refers to the last day of that month 
• Store in the original package in order to protect from moisture.  
• Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how 

to throw away medicines you no longer use. These measures will help protect the environment 
 
 
6. Contents of the pack and other information 
 
What Iasibon contains 
• The active substance is ibandronic acid. Each film-coated tablet contains 50 mg of ibandronic 

acid (as sodium monohydrate) 
 
The other ingredients are: 
• tablet core: povidone, microcrystalline cellulose, crospovidone, maize starch pregelatinised, 

glycerol dibehenate, colloidal anhydrous silica. 
• tablet coat: titanium dioxide (E171), lactose monohydrate, hypromellose (E464), macrogol 4000 
 
What Iasibon looks like and contents of the pack 
The film-coated tablets are white, round biconvex tablets supplied in Polyamide/Al/PVC - Aluminum 
foil blister. They are available in packs of 3, 6, 9, 28 and 84 tablets.  
Not all pack sizes may be marketed 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing Authorisation Holder 
Pharmathen S.A. 
Dervenakion 6  
Pallini 15351 
Attiki  
Greece 
 
Manufacturer  
Pharmathen S.A. 
Dervenakion 6  
Pallini 15351 
Attiki  
Greece 
 
And 
 
Pharmathen International S.A. 
Industrial Park Sapes, Street block 5 
69300 Sapes, Prefecture of Rodopi  
Greece 
 
For any information about this medicine, please contact the local representative of the Marketing 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


   101 
 

Authorisation Holder. 
 
België/Belgique/Belgien 
Pharmathen S.A. 
Tél/Tel: +30 210 66 04 300 
 

Lietuva 
SIA ELVIM 
Tel: +371 67808450 
 

България  
Alvogen Pharma Bulgaria Ltd 
Teл.: + 359 2  441 7136 
 

Luxembourg/Luxemburg 
Pharmathen S.A. 
Tél/Tel: +30 210 66 04 300 
 

Česká republika 
PHARMAGEN CZ s.r.o. 
Tel: +420 721 137 749 
 

Magyarország  
Pharmathen S.A. 
Tel.: +30 210 66 04 300 
 

Danmark 
Bluefish Pharmaceuticals AB 
Tlf: +46 8 51911600 
 

Malta 
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Deutschland 
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Nederland 
Glenmark Generics B.V.   
Tel: 0031 20 5226030 
 

Eesti (Estonia) 
SIA ELVIM 
Tel: +371 67808450 
 

Norge 
Pharmathen S.A. 
Tlf: +30 210 66 04 300 
 

Ελλάδα 
INNOVIS PHARMA AEBE  
Τηλ: +30 210 6664805-806 
 

Österreich  
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

España 
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Polska 
Pharmathen S.A. 
Tel.: +30 210 66 04 300 
 

France 
Pharmathen S.A. 
Tél: +30 210 66 04 300 
 

Portugal 
Pharmathen S.A. 
Tel: +30 210 66 04 300 

Hrvatska 
PROXIMUM d.o.o. 
Tel: +385 1 30 111 28 

România 
Alvogen Romania SRL  
Tel: +(40) 21 351 0286 
 

Ireland 
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Slovenija 
Pharmathen S.A. 
Tel: +30 210 66 04 300 

Ísland 
Alvogen ehf. 
Sími: +354 522 2900 
 

Slovenská republika  
PHARMAGEN CZ s.r.o. 
Tel: +420 721 137 749 
 

Italia 
Pharmathen S.A. 
Tel: +30 210 66 04 300 
 

Suomi/Finland 
Pharmathen S.A. 
Puh/Tel: +30 210 66 04 300 

Κύπρος 
The Star Medicines Importers Co. Ltd 
Τηλ: +357 25371056 

Sverige  
Pharmathen S.A. 
Tel: +30 210 66 04 300 



   102 
 

 
Latvija  
SIA ELVIM 
Tel: +371 67808450 
 

United Kingdom 
Aspire Pharma Ltd 
Tel: +44 1730 231148 
 

 
This leaflet was last revised in {MM/YYYY} 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET