Bonviva

1 

ANNEX I 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 

1. NAME OF THE MEDICINAL PRODUCT 

 

Bonviva 150 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each film-coated tablet contains 150 mg ibandronic acid (as sodium monohydrate). 

 

Excipients with known effect:  

Contains 154.6 mg anhydrous lactose (equivalent to 162.75 mg lactose monohydrate).  

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Film-coated tablet 

White to off white film-coated tablets, of oblong shape marked “BNVA” on one side, and “150” on 

the other side.  

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Treatment of osteoporosis in postmenopausal women at increased risk of fracture (see section 5.1). 

A reduction in the risk of vertebral fractures has been demonstrated, efficacy on femoral neck fractures 

has not been established. 

 

4.2 Posology and method of administration 

 

Posology 

The recommended dose is one 150 mg film-coated tablet once a month. The tablet should preferably 

be taken on the same date each month. 

 

Bonviva should be taken after an overnight fast (at least 6 hours) and 1 hour before the first food or 

drink (other than water) of the day (see section 4.5) or any other oral medicinal products or 

supplementation (including calcium). 

 

In case a dose is missed, patients should be instructed to take one Bonviva 150 mg tablet the morning 

after the tablet is remembered, unless the time to the next scheduled dose is within 7 days.  

Patients should then return to taking their dose once a month on their originally scheduled date. 

If the next scheduled dose is within 7 days, patients should wait until their next dose and then continue 

taking one tablet once a month as originally scheduled.  

Patients should not take two tablets within the same week. 

 

Patients should receive supplemental calcium and / or vitamin D if dietary intake is inadequate (see 

section 4.4 and section 4.5). 

 

The optimal duration of bisphosphonate treatment for osteoporosis has not been established. The need 

for continued treatment should be re-evaluated periodically based on the benefits and potential risks of 

Bonviva on an individual patient basis, particularly after 5 or more years of use. 

 



3 

Special populations 

Patients with renal impairment 

Bonviva is not recommended for patients with a creatinine clearance below 30 ml/min due to limited 

clinical experience (see section 4.4 and section 5.2). 

No dose adjustment is necessary for patients with mild or moderate renal impairment where creatinine 

clearance is equal or greater than 30 ml/min. 

 

Patients with hepatic impairment 

No dose adjustment is required (see section 5.2). 

 

Elderly population (>65 years) 

No dose adjustment is required (see section 5.2). 

 

Paediatric population 

There is no relevant use of Bonviva in children below 18 years, and Bonviva was not studied in this 

population. (see section 5.1 and section 5.2). 

 

Method of administration 

For oral use. 

 

- Tablets should be swallowed whole with a glass of water (180 to 240 ml) while the patient is 

sitting or standing in an upright position. Water with a high concentration of calcium should not 

be used. If there is a 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. 

- Patients should not lie down for 1 hour after taking Bonviva. 

- Water is the only drink that should be taken with Bonviva.  

- Patients should not chew or suck the tablet, because of a potential for oropharyngeal ulceration 

 

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 

 

Hypocalcaemia 

Existing hypocalcaemia must be corrected before starting Bonviva therapy. Other disturbances of bone 

and mineral metabolism should also be effectively treated. Adequate intake of calcium and vitamin D 

is important in all patients. 

 

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 Bonviva is given to patients with active upper gastrointestinal problems 

(e.g. known Barrett’s oesophagus, dysphagia, other oesophageal diseases, gastritis, duodenitis or 

ulcers). 

Adverse reactions such as oesophagitis, oesophageal ulcers and oesophageal erosions, in some cases 

severe and requiring hospitalisation, 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 to and be able to comply 

with the dosing instructions (see section 4.2). 



4 

Physicians should be alert to any signs or symptoms signaling a possible oesophageal reaction and 

patients should be instructed to discontinue Bonviva 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. 

 

Since Nonsteroidal Anti-Inflammatory medicinal products and bisphosphonates are both associated 

with gastrointestinal irritation, caution should be taken during concomitant administration. 

 

Osteonecrosis of the jaw 

Osteonecrosis of the jaw (ONJ) has been reported very rarely in the post marketing setting in patients 

receiving Bonviva for osteoporosis (see section 4.8).  

 

The start of treatment or of a new course of treatment should be delayed in patients with unhealed 

open soft tissue lesions in the mouth. 

 

A dental examination with preventive dentistry and an individual benefit-risk assessment is 

recommended prior to treatment with Bonviva in patients with concomitant risk factors. 

 

The following risk factors should be considered when evaluating a patient’s risk of developing ONJ:  

- Potency of the medicinal product that inhibit bone resorption (higher risk for highly potent 

compounds), route of administration (higher risk for parenteral administration) and cumulative 

dose of bone resorption therapy 

- Cancer, co-morbid conditions (e.g. anaemia, coagulopathies, infection), smoking 

- Concomitant therapies: corticosteroids, chemotherapy, angiogenesis inhibitors, radiotherapy to 

head and neck 

- Poor oral hygiene, periodontal disease, poorly fitting dentures, history of dental disease, invasive 

dental procedures e.g. tooth extractions 

 

All patients should be encouraged to maintain good oral hygiene, undergo routine dental check-ups, 

and immediately report any oral symptoms such as dental mobility, pain or swelling, or non-healing of 

sores or discharge during treatment with Bonviva. While on treatment, invasive dental procedures 

should be performed only after careful consideration and be avoided in close proximity to Bonviva 

administration. 

 

The management plan of the patients who develop ONJ should be set up in close collaboration 

between the treating physician and a dentist or oral surgeon with expertise in ONJ. Temporary 

interruption of Bonviva treatment should be considered until the condition resolves and contributing 

risk factors are mitigated where possible. 

  

 

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 



5 

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 impairment 

Due to limited clinical experience, Bonviva is not recommended for patients with a creatinine 

clearance below 30 ml/min (see section 5.2). 

 

Galactose intolerance 

This medicinal product contains lactose. Patients with rare hereditary problems of galactose 

intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this 

medicinal product. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

Medicinal product-Food Interaction  

Oral bioavailability of ibandronic acid is generally reduced in the presence of food. In particular, 

products containing calcium, including milk, and other multivalent cations (such as aluminium, 

magnesium, iron), are likely to interfere with absorption of Bonviva, which is consistent with findings 

in animal studies. Therefore, patients should fast overnight (at least 6 hours) before taking Bonviva 

and continue fasting for 1 hour following intake of Bonviva (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.  

 

Calcium supplements, antacids and some oral medicinal products containing multivalent cations 

Calcium supplements, antacids and some oral medicinal products containing multivalent cations (such 

as aluminium, magnesium, iron) are likely to interfere with the absorption of Bonviva. Therefore, 

patients should not take other oral medicinal products for at least 6 hours before taking Bonviva and 

for 1 hour following intake of Bonviva.  

 

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). 

 

H2 blockers or proton pump inhibitors  

Of over 1500 patients enrolled in study BM 16549 comparing monthly with daily dosing regimens of 

ibandronic acid, 14 % and 18 % of patients used histamine (H2) blockers or proton pump inhibitors 

after one and two years, respectively. Among these patients, the incidence of upper gastrointestinal 

events in the patients treated with Bonviva 150 mg once monthly was similar to that in patients treated 

with ibandronic acid 2.5 mg daily. 

 

In healthy male volunteers and postmenopausal women, intravenous administration of ranitidine 

caused an increase in ibandronic acid bioavailability of about 20 %, probably as a result of reduced 

gastric acidity. However, since this increase is within the normal variability of the bioavailability of 

ibandronic acid, no dose adjustment is considered necessary when Bonviva is administered with H2-

antagonists or other active substances which increase gastric pH. 

 



6 

4.6 Fertility, pregnancy and lactation 

Pregnancy 

Bonviva is only for use in postmenopausal women and must not be taken by women of childbearing 

potential. 

There are no adequate data from the use of ibandronic acid in pregnant women. Studies in rats have 

shown some reproductive toxicity (see section 5.3). The potential risk for humans is unknown. 

Bonviva 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. 

Bonviva should not be used during breast-feeding. 

Fertility 

There are no data on the effects of ibandronic acid from 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 Bonviva 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, ocular inflammation, (see paragraph 

“Description of selected adverse reactions” and section 4.4). 

The most frequently reported adverse reactions are arthralgia and influenza-like symptoms. These 

symptoms are typically in association with the first dose, generally of short duration, mild or moderate 

in intensity, and usually resolve during continuing treatment without requiring remedial measures (see 

paragraph “Influenza like illness”). 

Tabulated list of adverse reactions 

In table 1 a complete list  of known adverse reactions is presented. The safety of oral treatment with 

ibandronic acid 2.5 mg daily was evaluated in 1251 patients treated in 4 placebo-controlled clinical 

studies, with the large majority of patients coming from the pivotal three year fracture study 

(MF4411).  

In a two-year study in postmenopausal women with osteoporosis (BM 16549) the overall safety of 

Bonviva 150 mg once monthly and ibandronic acid 2.5 mg daily was similar. The overall proportion 

of patients who experienced an adverse reaction, was 22.7 % and 25.0 % for Bonviva 150 mg once 

monthly after one and two years, respectively. Most cases did not lead to cessation of therapy. 

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. 



7 

Table 1: Adverse reactions occurring in postmenopausal women receiving Bonviva 150 mg once 

monthly or ibandronic acid 2.5 mg daily in the phase III studies BM16549 and MF4411 and in post-

marketing experience. 
 

System Organ Class Common Uncommon Rare Very rare 

Immune system 

disorders 

 Asthma 

exacerbation 

Hypersensitivity 

reaction  

Anaphylactic 

reaction/shock*† 

 

Nervous system 

disorders 

Headache Dizziness   

Eye disorders   Ocular 

inflammation*† 

 

Gastrointestinal 

disorders* 

Oesophagitis, 

Gastritis, Gastro 

oesophageal reflux 

disease, Dyspepsia, 

Diarrhoea, 

Abdominal pain, 

Nausea 

Oesophagitis 

including 

oesophageal 

ulcerations or 

strictures and 

dysphagia, 

Vomiting, 

Flatulence 

Duodenitis  

Skin and subcutaneous 

tissues disorders 

Rash  Angioedema, 

Face oedema, 

Urticaria 

Stevens-Johnson 

Syndrome†, 

Erythema 

Multiforme†, 

Dermatitis 

Bullous† 

Musculoskeletal and 

connective tissue 

disorders 

Arthralgia, Myalgia, 

Musculoskeletal pain, 

Muscle cramp, 

Musculoskeletal 

stiffness 

Back pain Atypical 

subtrochanteric 

and diaphyseal 

femoral fractures†  

Osteonecrosis of 

jaw*†  

Osteonecrosis of 

the external 

auditory canal 

(bisphosphonate 

class adverse 

reaction)† 

General disorders and 

administration site 

conditions 

Influenza like illness* Fatigue   

*See further information below 

†Identified in post-marketing experience. 

 

Description of selected adverse reactions 

 

Gastrointestinal adverse reactions 

Patients with a previous history of gastrointestinal disease including patients with peptic ulcer without 

recent bleeding or hospitalisation, and patients with dyspepsia or reflux controlled by medication were 

included in the once monthly treatment study. For these patients, there was no difference in the 

incidence of upper gastrointestinal adverse events with the 150 mg once monthly regimen compared to 

the 2.5 mg daily regimen. 

 

Influenza-like illness 

Influenza-like illness includes events reported as acute phase reaction or symptoms including myalgia, 

arthralgia, fever, chills, fatigue, nausea, loss of appetite, or bone pain. 

 



8 

Osteonecrosis of jaw 

Cases of osteonecrosis of the jaw have been reported, predominantly in cancer patients treated with 

medicinal products that inhibit bone resorption, such as ibandronic acid (see section 4.4.) Cases of 

ONJ have been reported in the post marketing setting for ibandronic acid. 

 

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 overdose with Bonviva. 

However, based on a knowledge of this class of compounds, oral overdose may result in upper 

gastrointestinal adverse reactions (such as upset stomach, dyspepsia, oesophagitis, gastritis, or ulcer) 

or hypocalcaemia. Milk or antacids should be given to bind Bonviva, and any adverse reactions treated 

symptomatically. Owing 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 

 

Pharmacotherapeutic group: Medicinal products for treatment of bone diseases, bisphosphonates, ATC 

code: M05-BA06 

 

Mechanism of action 

Ibandronic acid is a highly potent bisphosphonate belonging to the nitrogen-containing group of 

bisphosphonates, which act selectively on bone tissue and specifically inhibit osteoclast activity 

without directly affecting bone formation. It does not interfere with osteoclast recruitment. Ibandronic 

acid leads to progressive net gains in bone mass and a decreased incidence of fractures through the 

reduction of elevated bone turnover towards premenopausal levels in postmenopausal women. 

 

Pharmacodynamic effects 

The pharmacodynamic action of ibandronic acid is inhibition of bone resorption. In vivo, ibandronic 

acid prevents experimentally induced bone destruction caused by cessation of gonadal function, 

retinoids, tumours or tumour extracts. In young (fast growing) rats, the endogenous bone resorption is 

also inhibited, leading to increased normal bone mass compared with untreated animals. 

Animal models confirm that ibandronic acid is a highly potent inhibitor of osteoclastic activity. In 

growing rats, there was no evidence of impaired mineralization even at doses greater than 5,000 times 

the dose required for osteoporosis treatment. 

Both daily and intermittent (with prolonged dose-free intervals) long-term administration in rats, dogs 

and monkeys was associated with formation of new bone of normal quality and maintained or 

increased mechanical strength even at doses in the toxic range. In humans, the efficacy of both daily 

and intermittent administration with a dose-free interval of 9-10 weeks of ibandronic acid was 

confirmed in a clinical trial (MF 4411), in which ibandronic acid demonstrated anti-fracture efficacy. 

 

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


9 

In animal models ibandronic acid produced biochemical changes indicative of dose-dependent 

inhibition of bone resorption, including suppression of urinary biochemical markers of bone collagen 

degradation (such as deoxypyridinoline, and cross-linked N-telopeptides of type I collagen (NTX)). 

 

In a Phase 1 bioequivalence study conducted in 72 postmenopausal women receiving 150 mg orally 

every 28 days for a total of four doses, inhibition in serum CTX following the first dose was seen as 

early as 24 hours post-dose (median inhibition 28 %), with median maximal inhibition (69 %) seen 

6 days later. Following the third and fourth dose, the median maximum inhibition 6 days post dose 

was 74 % with reduction to a median inhibition of 56 % seen 28 days following the fourth dose. With 

no further dosing, there is a loss of suppression of biochemical markers of bone resorption. 

 

Clinical efficacy 

Independent risk factors, for example, low BMD, age, the existence of previous fractures, a family 

history of fractures, high bone turnover and low body mass index should be considered in order to 

identify women at increased risk of osteoporotic fractures. 

 

Bonviva 150 mg once monthly 

 

Bone mineral density (BMD) 

Bonviva 150 mg once monthly was shown to be at least as effective as ibandronic acid 2.5 mg daily at 

increasing BMD in a two year, double-blind, multicentre study (BM 16549) of postmenopausal 

women with osteoporosis (lumbar spine BMD T score below -2.5 SD at baseline). This was 

demonstrated in both the primary analysis at one year and in the confirmatory analysis at two years 

endpoint (Table 2). 

 

Table 2: Mean relative change from baseline of lumbar spine, total hip, femoral neck and trochanter 

BMD after one year (primary analysis) and two years of treatment (Per-Protocol Population) in study 

BM 16549. 

 

 One year data in study BM 16549 Two year data in study 

BM 16549 

Mean relative changes 

from baseline % [95% CI]  

ibandronic acid 

2.5 mg daily 

(N=318) 

Bonviva 

150 mg once 

monthly 

(N=320) 

ibandronic acid 

2.5 mg daily 

(N=294) 

Bonviva 

150 mg once 

monthly 

(N=291) 

Lumbar spine L2-L4 BMD 3.9 [3.4, 4.3]  4.9 [4.4, 5.3]  5.0 [4.4, 5.5]  6.6 [6.0, 7.1]  

Total hip BMD 2.0 [1.7, 2.3]  3.1 [2.8, 3.4]  2.5 [2.1, 2.9]  4.2 [3.8, 4.5]  

Femoral neck BMD 1.7 [1.3, 2.1]  2.2 [1.9, 2.6]  1.9 [1.4, 2.4]  3.1 [2.7, 3.6]  

Trochanter BMD 3.2 [2.8, 3.7]  4.6 [4.2, 5.1]  4.0 [3.5, 4.5]  6.2 [5.7, 6.7]  

 

Furthermore, Bonviva 150 mg once monthly was proven superior to ibandronic acid 2.5 mg daily for 

increases in lumbar spine BMD in a prospectively planned analysis at one year, p=0.002, and at two 

years, p<0.001. 

 

At one year (primary analysis), 91.3 % (p=0.005) of patients receiving Bonviva 150 mg once monthly 

had a lumbar spine BMD increase above or equal to baseline (BMD responders), compared with 

84.0 % of patients receiving ibandronic acid 2.5 mg daily. At two years, 93.5 % (p=0.004) and 86.4 % 

of patients receiving Bonviva 150 mg once monthly or ibandronic acid 2.5 mg daily, respectively, 

were responders.  

 

For total hip BMD, 90.0 % (p<0.001) of patients receiving Bonviva 150 mg once monthly and 76.7 % 

of patients receiving ibandronic acid 2.5 mg daily had total hip BMD increases above or equal to 

baseline at one year. At two years  93.4 % (p<0.001) of patients receiving Bonviva 150 mg once 



10 

monthly and 78.4 %, of patients receiving ibandronic acid 2.5 mg daily had total hip BMD increases 

above or equal to baseline. 

 

When a more stringent criterion is considered, which combines both lumbar spine and total hip BMD, 

83.9 % (p<0.001) and 65.7 % of patients receiving Bonviva 150 mg once monthly or ibandronic acid 

2.5 mg daily, respectively, were responders at one year. At two years, 87.1 % (p<0.001) and 70.5 %,of 

patients met this criterion in the 150 mg monthly and 2.5 mg daily arms respectively. 

 

Biochemical markers of bone turn-over 

Clinically meaningful reductions in serum CTX levels were observed at all time points measured, i.e. 

months 3, 6, 12 and 24. After one year (primary analysis) the median relative change from baseline 

was -76 % for Bonviva 150 mg once monthly and -67 % for ibandronic acid 2.5 mg daily. At two 

years the median relative change was -68 % and -62 %, in the 150 mg monthly and 2.5 mg daily arms 

respectively.  

 

At one year, 83.5 % (p= 0.006) of patients receiving Bonviva 150 mg once monthly and 73.9 % of 

patients receiving ibandronic acid 2.5 mg daily were identified as responders (defined as a decrease 

≥50 % from baseline). At two years 78.7 % (p=0.002) and 65.6 % of patients were identified as 

responders in the 150 mg monthly and 2.5 mg daily arms respectively. 

 

Based on the results of study BM 16549, Bonviva 150 mg once monthly is expected to be at least as 

effective in preventing fractures as ibandronic acid 2.5 mg daily. 

 

Ibandronic acid 2.5 mg daily 

 

In the initial three-year, randomised, double-blind, placebo-controlled, fracture study (MF 4411), a 

statistically significant and medically relevant decrease in the incidence of new radiographic 

morphometric and clinical vertebral fractures was demonstrated (table 3). In this study, ibandronic 

acid was evaluated at oral doses of 2.5 mg daily and 20 mg intermittently as an exploratory regimen. 

Ibandronic acid was taken 60 minutes before the first food or drink of the day (post-dose fasting 

period). The study enrolled women aged 55 to 80 years, who were at least 5 years postmenopausal, 

who had a BMD at lumbar spine of 2 to 5 SD below the premenopausal mean (T-score) in at least one 

vertebra [L1-L4], and who had one to four prevalent vertebral fractures. All patients received 500 mg 

calcium and 400 IU vitamin D daily. Efficacy was evaluated in 2,928 patients. ibandronic acid 2.5 mg 

administered daily, showed a statistically significant and medically relevant reduction in the incidence 

of new vertebral fractures. This regimen reduced the occurrence of new radiographic vertebral 

fractures by 62 % (p=0.0001) over the three year duration of the study. A relative risk reduction of 

61 % was observed after 2 years (p=0.0006). No statistically significant difference was attained after 1 

year of treatment (p=0.056). The anti-fracture effect was consistent over the duration of the study. 

There was no indication of a waning of the effect over time.  

The incidence of clinical vertebral fractures was also significantly reduced by 49 % (p=0.011). The 

strong effect on vertebral fractures was furthermore reflected by a statistically significant reduction of 

height loss compared to placebo (p<0.0001). 

 



11 

Table 3: Results from 3 years fracture study MF 4411 (%, 95 % CI) 

Placebo 

(N=974) 

ibandronic acid 2.5 mg daily 

(N=977) 

Relative Risk Reduction 

New morphometric vertebral 

fractures 

62 % (40.9, 75.1) 

Incidence of new morphometric 

vertebral fractures 

9.56 % (7.5, 11.7) 4.68 % (3.2,6.2) 

Relative risk reduction of clinical 

vertebral fracture 

49 %  

(14.03, 69.49) 

Incidence of clinical vertebral 

fracture 

5.33 % 

(3.73, 6.92) 

2.75 % 

(1.61, 3.89) 

BMD – mean change relative to 

baseline lumbar spine at year 3 

1.26 % (0.8, 1.7) 6.54 % (6.1, 7.0) 

BMD – mean change relative to 

baseline total hip at year 3 

-0.69 %

(-1.0, -0.4)

3.36 % 

(3.0, 3.7) 

The treatment effect of ibandronic acid was further assessed in an analysis of the subpopulation of 

patients who at baseline had a lumbar spine BMD T-score below –2.5. The vertebral fracture risk 

reduction was very consistent with that seen in the overall population. 

Table 4: Results from 3 years fracture study MF 4411 (%, 95 % CI) for patients with lumbar spine 

BMD T-score below –2.5 at baseline 

Placebo 

(N=587) 

ibandronic acid 2.5 mg daily 

(N=575) 

Relative Risk Reduction 

New morphometric vertebral 

fractures 

59 % (34.5, 74.3) 

Incidence of new morphometric 

vertebral fractures 

12.54 % (9.53, 15.55) 5.36 % (3.31, 7.41) 

Relative risk reduction of clinical 

vertebral fracture 

50 % (9.49, 71.91) 

Incidence of clinical vertebral 

fracture 

6.97 % (4.67, 9.27) 3.57 % (1.89, 5.24) 

BMD – mean change relative to 

baseline lumbar spine at year 3 

1.13 % (0.6, 1.7) 7.01 % (6.5, 7.6) 

BMD – mean change relative to 

baseline total hip at year 3 

-0.70 % (-1.1, -0.2) 3.59 % (3.1, 4.1) 

In the overall patient population of the study MF4411, no reduction was observed for non-vertebral 

fractures, however daily ibandronic acid appeared to be effective in a high-risk subpopulation (femoral 

neck BMD T-score < -3.0), where a non-vertebral fracture risk reduction of 69% was observed. 

Daily treatment with 2.5 mg resulted in progressive increases in BMD at vertebral and nonvertebral 

sites of the skeleton. 

Three-year lumbar spine BMD increase compared to placebo was 5.3 % and 6.5 % compared to 

baseline. Increases at the hip compared to baseline were 2.8 % at the femoral neck, 3.4 % at the total 

hip, and 5.5 % at the trochanter. 

Biochemical markers of bone turnover (such as urinary CTX and serum Osteocalcin) showed the 

expected pattern of suppression to premenopausal levels and reached maximum suppression within a 

period of 3-6 months. 

A clinically meaningful reduction of 50 % of biochemical markers of bone resorption was observed as 

early as one month after start of treatment with ibandronic acid 2.5 mg. 



12 

Following treatment discontinuation, there is a reversion to the pathological pre-treatment rates of 

elevated bone resorption associated with postmenopausal osteoporosis. 

The histological analysis of bone biopsies after two and three years of treatment of postmenopausal 

women showed bone of normal quality and no indication of a mineralization defect. 

 

Paediatric population (see section 4.2 and section 5.2) 

Bonviva was not studied in the paediatric population, therefore no efficacy or safety data are available 

for this patient population.  

 

5.2 Pharmacokinetic properties 

 

The primary pharmacological effects of ibandronic acid on bone are not directly related to actual 

plasma concentrations, as demonstrated by various studies in animals and humans.  

 

Absorption  

The absorption of ibandronic acid in the upper gastrointestinal tract is rapid after oral administration 

and plasma concentrations increase in a dose-proportional manner up to 50 mg oral intake, with 

greater than dose-proportional increases seen above this dose. 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. 

There is no meaningful reduction in bioavailability provided ibandronic acid is taken 60 minutes 

before the first food of the day. Both bioavailability and BMD gains are reduced when food or 

beverage is taken less than 60 minutes after ibandronic acid is ingested. 

 

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 85 % - 87 % (determined in vitro at therapeutic concentrations), and thus there is a low 

potential for interaction with other medicinal products due to displacement. 

 

Biotransformation 

There is no evidence that ibandronic acid is metabolised in animals or humans. 

 

Elimination 

The absorbed fraction of ibandronic acid is removed from the circulation via bone absorption 

(estimated to be 40-50 % in postmenopausal women) 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, the apparent terminal half-life is generally in the 

range of 10-72 hours. As the values calculated are largely a function of the duration of study, the dose 

used, and assay sensitivity, the true terminal half-life is likely to be substantially longer, in common 

with other bisphosphonates. 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 considered to reflect the uptake by bone. 

 

The secretory pathway appears not 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. 

 



13 

Pharmacokinetics in special clinical situations 

 

Gender 

Bioavailability and pharmacokinetics of ibandronic acid are similar in men and women. 

 

Race 

There is no evidence for any clinically relevant inter-ethnic differences between Asians and 

Caucasians in ibandronic acid disposition. There are few data available on patients of African origin. 

 

Patients with renal impairment  

Renal clearance of ibandronic acid in patients with various degrees of renal impairment is linearly 

related to creatinine clearance. 

No dose adjustment is necessary for patients with mild or moderate renal impairment (CLcr equal or 

greater than 30 ml/min), as shown in study BM 16549 where the majority of patients had mild to 

moderate renal impairment. 

Subjects with severe renal failure (CLcr less than 30 ml/min) receiving daily oral administration of 

10 mg ibandronic acid for 21 days, had 2-3 fold higher plasma concentrations than subjects with 

normal renal function and total clearance of ibandronic acid was 44 ml/min. After intravenous 

administration of 0.5 mg, total, renal, and non-renal clearances decreased by 67 %, 77 % and 50 %, 

respectively, in subjects with severe renal failure but there was no reduction in tolerability associated 

with the increase in exposure. Due to the limited clinical experience, Bonviva is not recommended in 

patients with severe renal impairment (see section 4.2 and section 4.4). The pharmacokinetics of 

ibandronic acid was not assessed in patients with end-stage renal disease managed by other than 

hemodialysis. The pharmacokinetics of ibandronic acid in these patients is unknown, and ibandronic 

acid should not be used under these circumstances. 

 

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 which is not metabolised but is cleared 

by renal excretion and by uptake into bone. Therefore dose adjustment is not necessary in patients 

with hepatic impairment. 

 

Elderly population (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 Bonviva in these age groups. 

 

5.3 Preclinical safety data 

 

Toxic effects, e.g signs of renal damage, were observed in dogs only at exposures considered 

sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.  

 

Mutagenicity/Carcinogenicity: 

No indication of carcinogenic potential was observed. Tests for genotoxicity revealed no evidence of 

genetic activity for ibandronic acid. 

 

Reproductive toxicity: 

There was no evidence for a direct foetal toxic or teratogenic effect of ibandronic acid in orally treated 

rats and rabbits and there were no adverse effects on the development in F1 offspring in rats at an 

extrapolated exposure of at least 35 times above human exposure. 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 



14 

toxicity studies in the rat were those observed with bisphosphonates as a class. They include a 

decreased number of implantation sites, interference with natural delivery (dystocia), and an increase 

in visceral variations (renal pelvis ureter syndrome). 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Tablet core 

Lactose monohydrate 

Povidone 

Cellulose, microcrystalline 

Crospovidone 

Stearic acid 

Silica, colloidal anhydrous 

 

Tablet coat 

Hypromellose 

Titanium dioxide (E 171) 

Talc 

Macrogol 6,000 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

5 years. 

 

6.4 Special precautions for storage 

 

This medicinal product does not require any special storage conditions. 

 

6.5 Nature and contents of container 

 

Bonviva 150 mg film-coated tablets are supplied in blisters (PVC/PVDC, sealed with aluminium foil) 

containing 1 or 3 tablets. 

 

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 

 

Atnahs Pharma Netherlands B.V. 

Copenhagen Towers,  

Ørestads Boulevard 108, 5.tv 

DK-2300 København S  

Denmark 

 

 



15 

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/03/265/003 

EU/1/03/265/004 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 23 February 2004 

Date of latest renewal: 18 December 2013 

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. 



16 

1. NAME OF THE MEDICINAL PRODUCT

Bonviva 3 mg solution for injection 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

One pre-filled syringe of 3 ml solution contains 3 mg ibandronic acid (as sodium monohydrate). 

The concentration of ibandronic acid in the solution for injection is 1mg per ml. 

For the full list of excipients, see section 6.1. 

3. PHARMACEUTICAL FORM

Solution for injection. 

Clear, colourless solution. 

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Treatment of osteoporosis in postmenopausal women at increased risk of fracture (see section 5.1). 

A reduction in the risk of vertebral fractures has been demonstrated, efficacy on femoral neck fractures 

has not been established. 

4.2 Posology and method of administration 

Patients treated with Bonviva should be given the package leaflet and the patient reminder card. 

Posology 

The recommended dose of ibandronic acid is 3 mg, administered as an intravenous injection over 15 -

 30 seconds, every three months. 

Patients must receive supplemental calcium and vitamin D (see section 4.4 and section 4.5), 

If a dose is missed, the injection should be administered as soon as convenient. Thereafter, injections 

should be scheduled every 3 months from the date of the last injection. 

The optimal duration of bisphosphonate treatment for osteoporosis has not been established. The need 

for continued treatment should be re-evaluated periodically based on the benefits and potential risks of 

Bonviva on an individual patient basis, particularly after 5 or more years of use. 

Special populations 

Patients with renal impairment 

Bonviva injection is not recommended for use in patients who have a serum creatinine above 

200 μmol/l (2.3 mg/dl) or who have a creatinine clearance (measured or estimated) below 30 ml/min, 

because of limited clinical data available from studies including such patients (see section 4.4 and 

section 5.2). 

No dose adjustment is necessary for patients with mild or moderate renal impairment where serum 

creatinine is equal or below 200 μmol/l (2.3 mg/dl) or where creatinine clearance (measured or 

estimated) is equal or greater than 30 ml/min. 

Patients with hepatic impairment 

No dose adjustment is required (see section 5.2). 



17 

 

Elderly population (>65 years) 

No dose adjustment is required (see section 5.2). 

 

Paediatric population 

There is no relevant use of Bonviva in children below 18 years, and Bonviva was not studied in this 

population  (see section 5.1 and 5.2).  

 

Method of administration 

For intravenous use over 15 - 30 seconds, every three months. 

 

Strict adherence to the intravenous administration route is required (see section 4.4). 
 

4.3 Contraindications 

 

- Hypersensitivity to ibandronic acid or to any of the excipients listed in section 6.1 

- Hypocalcaemia 

 

4.4 Special warnings and precautions for use 

 

Administration failures 

Care must be taken not to administer Bonviva injection via intra-arterial or paravenous administration 

as this could lead to tissue damage. 

 

Hypocalcaemia 

Bonviva, like other bisphosphonates administered intravenously, may cause a transient decrease in 

serum calcium values. 

Existing hypocalcaemia must be corrected before starting Bonviva injection therapy. Other 

disturbances of bone and mineral metabolism should also be effectively treated before starting 

Bonviva injection therapy.  

 

All patients must receive adequate supplemental calcium and vitamin D. 

 

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 Bonviva 

intravenous injection is administered. If anaphylactic or other severe hypersensitivity/allergic reactions 

occur, immediately discontinue the injection and initiate appropriate treatment. 

 

Renal impairment 

Patients with concomitant diseases, or who use medicinal products which have potential for 

undesirable effects on the kidney, should be reviewed regularly in line with good medical practice 

during treatment.  

 

Due to limited clinical experience, Bonviva injection is not recommended for patients with a serum 

creatinine above 200 μmol/l (2.3 mg/dl) or with a creatinine clearance below 30 ml/min (see section 

4.2 and section 5.2).  

 

Patients with cardiac impairment 

Overhydration should be avoided in patients at risk of cardiac failure. 

 

Osteonecrosis of the jaw 

Osteonecrosis of the jaw (ONJ) has been reported very rarely in the post marketing setting in patients 

receiving Bonviva for osteoporosis (see section 4.8).  

 



18 

The start of treatment or of a new course of treatment should be delayed in patients with unhealed 

open soft tissue lesions in the mouth. 

A dental examination with preventive dentistry and an individual benefit-risk assessment is 

recommended prior to treatment with Bonviva in patients with concomitant risk factors. 

The following risk factors should be considered when evaluating a patient’s risk of developing ONJ: 

- Potency of the medicinal product that inhibit bone resorption (higher risk for highly potent

compounds), route of administration (higher risk for parenteral administration) and cumulative

dose of bone resorption therapy

- Cancer, co-morbid conditions (e.g. anaemia, coagulopathies, infection), smoking

- Concomitant therapies: corticosteroids, chemotherapy, angiogenesis inhibitors, radiotherapy to

head and neck

- Poor oral hygiene, periodontal disease, poorly fitting dentures, history of dental disease,

invasive dental procedures e.g. tooth extractions

All patients should be encouraged to maintain good oral hygiene, undergo routine dental check-ups, 

and immediately report any oral symptoms such as dental mobility, pain or swelling, or non-healing of 

sores or discharge during treatment with Bonviva. While on treatment, invasive dental procedures 

should be performed only after careful consideration and be avoided in close proximity to Bonviva 

administration. 

The management plan of the patients who develop ONJ should be set up in close collaboration 

between the treating physician and a dentist or oral surgeon with expertise in ONJ. Temporary 

interruption of Bonviva treatment should be considered until the condition resolves and contributing 

risk factors are mitigated where possible. 

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. 

Bonviva is 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.  



19 

 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

Bonviva is only for use in postmenopausal women and must not be taken by women of child bearing 

potential. 

There are no adequate data from the use of ibandronic acid in pregnant women. Studies in rats have 

shown some reproductive toxicity (see section 5.3). The potential risk for humans is unknown. 

Bonviva 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. Bonviva should not be used during  breastfeeding. 

 

Fertility 

There are no data on the effects of ibandronic acid from 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 Bonviva 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). 

The most frequently reported adverse reactions are arthralgia and influenza-like symptoms. These 

symptoms are typically in association with the first dose, generally of short duration, mild or moderate 

in intensity, and usually resolve during continuing treatment without requiring remedial measures 

(please see paragraph “Influenza like illness”). 

 

Tabulated list of adverse reactions 

In table 1 a complete list of known adverse reactions is presented.  

The safety of oral treatment with ibandronic acid  2.5 mg  daily was evaluated in 1251 patients treated 

in 4 placebo-controlled clinical studies, with the large majority of patients coming from the pivotal 

three-year fracture  study (MF 4411).  

 

In the pivotal two-year study in postmenopausal women with osteoporosis (BM16550), the overall 

safety of intravenous injection of Bonviva 3 mg every 3 months and oral ibandronic acid 2.5 mg daily 

were shown to be similar. The overall proportion of patients who experienced an adverse reaction was 

26.0 % and 28.6 % for Bonviva 3 mg injection every 3 months after one year and two years, 

respectively. Most cases of adverse reactions did not lead to cessation of therapy. 

 

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. 
 



20 

Table 1: Adverse  reactions occurring in postmenopausal women receiving Bonviva 3 mg injection 

every 3 months or ibandronic acid 2.5 mg daily in the phase III studies BM16550 and MF 4411, and in 

post-marketing experience.  
  
System Organ 

Class 

Common Uncommon Rare Very rare 

Immune system 

disorders 

 Asthma 

exacerbation 

Hypersensitivity 

reaction 

Anaphylactic 

reaction/shock*† 

 

Nervous system 

disorders 

Headache    

Eye disorders   Ocular 

inflammation*† 

 

Vascular 

disorders 

 Phlebitis/ 

thrombophlebitis 

  

Gastrointestinal 

disorders 

Gastritis, Dyspepsia, 

Diarrhoea, 

Abdominal pain, 

Nausea, Constipation 

   

Skin and 

subcutaneous 

tissues disorders 

Rash  Angioedema, 

Facial 

swelling/oedema, 

Urticaria 

Stevens-Johnson 

Syndrome†, 

Erythema 

Multiforme†, 

Dermatitis 

Bullous† 

Musculoskeletal 

and , connective 

tissue disorders 

Arthralgia, Myalgia, 

Musculoskeletal 

pain, Back pain 

Bone pain Atypical 

subtrochanteric 

and diaphyseal 

femoral 

fractures†  

Osteonecrosis of 

jaw*†  

Osteonecrosis of 

the external 

auditory canal 

(bisphosphonate 

class adverse 

reaction)†  

General 

disorders and 

administration 

site conditions 

Influenza like 

illness*, Fatigue 

Injection site 

reactions, Asthenia 

  

*See further information below 

†Identified in post-marketing experience. 

 

Description of selected adverse reactions 

 

Influenza-like illness 

Influenza-like illness includes events reported as acute phase reaction or symptoms, including 

myalgia, arthralgia, fever, chills, fatigue, nausea, loss of appetite, and bone pain.  

 

Osteonecrosis of the jaw 

Cases of osteonecrosis of the jaw have been reported, predominantly in cancer patients treated with 

medicinal products that inhibit bone resorption, such as ibandronic acid (see section 4.4.) Cases of 

ONJ have been reported in the post marketing setting for ibandronic acid.  

 

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. 

 



21 

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 Bonviva. 

 

Based on knowledge of this class of compounds, intravenous overdosage may result in hypocalcaemia, 

hypophosphataemia, and hypomagnesaemia. Clinically relevant reductions in serum levels of calcium, 

phosphorus, and magnesium should be corrected by intravenous administration of calcium gluconate, 

potassium or sodium phosphate, and magnesium sulfate, respectively. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: Medicinal products for treatment of bone diseases, bisphosphonates, ATC 

code: M05BA06 

 

Mechanism of action 

Ibandronic acid is a highly potent bisphosphonate belonging to the nitrogen-containing group of 

bisphosphonates, which act selectively on bone tissue and specifically inhibit osteoclast activity 

without directly affecting bone formation. It does not interfere with osteoclast recruitment. Ibandronic 

acid leads to progressive net gains in bone mass and a decreased incidence of fractures through the 

reduction of elevated bone turnover towards premenopausal levels in postmenopausal women. 

 

Pharmacodynamic effects 

The pharmacodynamic action of ibandronic acid is inhibition of bone resorption. In vivo, ibandronic 

acid prevents bone destruction experimentally induced by cessation of gonadal function, retinoids, 

tumours or tumour extracts. In young (fast growing) rats, the endogenous bone resorption is also 

inhibited, leading to increased normal bone mass compared with untreated animals. 

 

Animal models confirm that ibandronic acid is a highly potent inhibitor of osteoclastic activity. In 

growing rats, there was no evidence of impaired mineralisation even at doses greater than 5,000 times 

the dose required for osteoporosis treatment. 

 

Both daily and intermittent (with prolonged dose-free intervals) long-term administration in rats, dogs 

and monkeys was associated with formation of new bone of normal quality and maintained or 

increased mechanical strength even at doses in the toxic range. In humans, the efficacy of both daily 

and intermittent administration with a dose-free interval of 9 - 10 weeks of ibandronic acid was 

confirmed in a clinical trial (MF 4411), in which ibandronic acid demonstrated anti-fracture efficacy. 

 

In animal models ibandronic acid produced biochemical changes indicative of dose-dependent 

inhibition of bone resorption, including suppression of urinary biochemical markers of bone collagen 

degradation (such as deoxypyridinoline, and cross-linked N-telopeptides of type I collagen (NTX)). 

 

Both daily, intermittent (with a dose-free interval of 9 - 10 weeks per quarter) oral doses as well as 

intravenous doses of ibandronic acid in postmenopausal women produced biochemical changes 

indicative of dose-dependent inhibition of bone resorption. 

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


22 

 

Bonviva intravenous injection decreased levels of serum C-telopeptide of the alpha chain of Type I 

collagen (CTX) within 3 - 7 days of starting treatment and decreased levels of osteocalcin within 

3 months. 

 

Following treatment discontinuation, there is a reversion to the pathological pre-treatment rates of 

elevated bone resorption associated with postmenopausal osteoporosis. 

 

The histological analysis of bone biopsies after two and three years of treatment of postmenopausal 

women with doses of oral ibandronic acid 2.5 mg daily and intermittent intravenous doses of up to 

1 mg every 3 months showed bone of normal quality and no indication of a mineralisation defect. An 

expected decrease in bone turnover, normal quality of bone and absence of defects in mineralization 

were also seen after two years of treatment with Bonviva 3 mg injection. 

 

Clinical efficacy 

Independent risk factors, for example, low BMD, age, the existence of previous fractures, a family 

history of fractures, high bone turnover and low body mass index should be considered in order to 

identify women at increased risk of osteoporotic fractures. 

 

Bonviva 3 mg injection every 3 months 

 

Bone mineral density (BMD) 

Bonviva 3 mg intravenous injection, administered every 3 months, was shown to be at least as 

effective as oral ibandronic acid 2.5 mg daily in a 2-year, randomised, double-blind, multicentre, non-

inferiority study (BM16550) of postmenopausal women (1386 women aged 55 - 80) with osteoporosis 

(lumbar spine BMD T-score below -2.5 SD at baseline). This was demonstrated in both the primary 

analysis at one year and in the confirmatory analysis at two years endpoint (Table 2). 

 

The primary analysis of data from study BM16550 at one year and the confirmatory analysis at 2 years 

demonstrated the non-inferiority of 3 mg every 3 months injection dosing regimen compared to 2.5 mg 

oral daily dosing regimen, in terms of mean increases in BMD at lumbar spine, total hip, femoral neck 

and trochanter (Table 2). 

 

Table 2: Mean relative change from baseline of lumbar spine, total hip, femoral neck and trochanter 

BMD after one year (primary analysis) and two years of treatment (Per-Protocol Population) in study 

BM 16550. 

 

 One year data in study BM 16550 Two year data in study 

BM 16550 

Mean relative changes 

from baseline % [95% CI]  

ibandronic acid 

2.5 mg daily 

(N=377) 

Bonviva 3 mg 

injection every 

3 months 

(N=365) 

ibandronic 

acid 2.5 mg 

daily 

(N=334) 

Bonviva 3 mg 

injection every 

3 months 

(N=334) 

Lumbar spine L2-L4 BMD 3.8 [3.4, 4.2] 4.8 [4.5, 5.2] 4.8 [4.3, 5.4] 6.3 [5.7, 6.8] 

Total hip BMD 1.8 [1.5, 2.1] 2.4 [2.0, 2.7] 2.2 [1.8, 2.6] 3.1 [2.6, 3.6] 

Femoral neck BMD 1.6 [1.2, 2.0] 2.3 [1.9, 2.7] 2.2 [1.8, 2.7] 2.8 [2.3, 3.3] 

Trochanter BMD 3.0 [2.6, 3.4] 3.8 [3.2, 4.4] 3.5 [3.0, 4.0] 4.9 [4.1, 5.7] 

 

Furthermore, Bonviva 3 mg injection every 3 months was proven superior to oral ibandronic acid 

2.5 mg daily for increases in lumbar spine BMD in a prospectively planned analysis at one year, 

p<0.001, and at two years, p<0.001.   

 



23 

For lumbar spine BMD, 92.1 % of patients receiving 3 mg injection every 3 months increased or 

maintained their BMD after 1 year of treatment (i.e. were responders) compared with 84.9 % of 

patients receiving oral 2.5 mg daily (p=0.002). After 2 years of treatment, 92.8 % of patients receiving 

3 mg injections and 84.7 % of patient receiving 2.5 mg oral therapy had increased or maintained 

lumbar spine BMD (p=0.001). 

 

For total hip BMD, 82.3 % of patients receiving 3 mg injection every 3 months were responders at one 

year, compared with 75.1 % of patients receiving 2.5 mg daily orally (p=0.02). After 2 years of 

treatment, 85.6 % of patients receiving 3 mg injections and 77.0 % of patient receiving 2.5 mg oral 

therapy had increased or maintained total hip BMD (p=0.004). 

 

The proportion of patients who increased or maintained their BMD at one year at both lumbar spine 

and total hip was 76.2 % in the 3 mg injection every 3 months arm and 67.2 % in the 2.5 mg daily 

orally arm (p=0.007). At two years, 80.1 % and 68.8 % of patients met this criterion in the 3 mg every 

3 months injection arm and the 2.5 mg daily arm (p=0.001). 

 

Biochemical markers of bone turn-over 

Clinically meaningful reductions in serum CTX levels were observed at all time points measured. At 

12 months median relative changes from baseline were –58.6 % for the intravenous injection of 3 mg 

every 3 months regimen and –62.6 % for oral 2.5 mg daily regimen. In addition, 64.8 % of patients 

receiving 3 mg every 3 months injection were identified as responders (defined as a decrease ≥50 % 

from baseline), compared with 64.9 % of patients receiving 2.5 mg daily orally. Serum CTX 

reduction was maintained over the 2 years, with more than half of the patients identified as responders 

in both treatment groups. 

 

Based on the results of study BM 16550, Bonviva 3 mg intravenous injection, administered every 3 

months is expected to be at least as effective in preventing fractures as the oral regimen of ibandronic 

acid 2.5 mg daily. 

 

Ibandronic acid 2.5 mg daily tablets 

 

In the initial three-year, randomised, double-blind, placebo-controlled, fracture study (MF 4411), a 

statistically significant and medically relevant decrease in the incidence of new radiographic 

morphometric and clinical vertebral fractures was demonstrated (table 3). In this study, ibandronic 

acid was evaluated at oral doses of 2.5 mg daily and 20 mg intermittently as an exploratory regimen. 

Ibandronic acid was taken 60 minutes before the first food or drink of the day (post-dose fasting 

period). The study enrolled women aged 55 to 80 years, who were at least 5 years postmenopausal, 

who had a BMD at the lumbar spine of -2 to -5 SD below the premenopausal mean (T-score) in at 

least one vertebra [L1-L4], and who had one to four prevalent vertebral fractures. All patients received 

500 mg calcium and 400 IU vitamin D daily. Efficacy was evaluated in 2,928 patients. Ibandronic acid 

2.5 mg administered daily, showed a statistically significant and medically relevant reduction in the 

incidence of new vertebral fractures. This regimen reduced the occurrence of new radiographic 

vertebral fractures by 62 % (p=0.0001) over the three year duration of the study. A relative risk 

reduction of 61 % was observed after 2 years (p=0.0006). No statistically significant difference was 

attained after 1 year of treatment (p=0.056). The anti-fracture effect was consistent over the duration 

of the study. There was no indication of a waning of the effect over time.  

 

The incidence of clinical vertebral fractures was also significantly reduced by 49 % after 3 years 

(p=0.011). The strong effect on vertebral fractures was furthermore reflected by a statistically 

significant reduction of height loss compared to placebo (p<0.0001). 

 



24 

Table 3: Results from 3 years fracture study MF 4411 (%, 95 % CI) 

 

 Placebo 

(N=974) 

ibandronic acid 2.5 mg daily 

(N=977) 

Relative risk reduction 

New morphometric vertebral 

fractures 

 62% (40.9, 75.1) 

Incidence of new morphometric 

vertebral fractures 

9.56% (7.5, 11.7) 4.68% (3.2, 6.2) 

Relative risk reduction of clinical 

vertebral fracture 

 49%  

(14.03, 69.49) 

Incidence of clinical vertebral 

fracture 

5.33% (3.73, 6.92) 2.75%  

(1.61, 3.89) 

BMD – mean change relative to 

baseline lumbar spine at year 3 

1.26% (0.8, 1.7) 6.54% (6.1, 7.0) 

BMD – mean change relative to 

baseline total hip at year 3 

-0.69% 

(-1.0, -0.4) 

3.36% 

(3.0, 3.7) 

 

The treatment effect of ibandronic acid was further assessed in an analysis of the subpopulation of 

patients who, at baseline, had a lumbar spine BMD T-score below –2.5 (table 4). The vertebral 

fracture risk reduction was very consistent with that seen in the overall population. 

 

Table 4: Results from 3 years fracture study MF 4411 (%, 95 % CI) for patients with lumbar spine 

BMD T-score below –2.5 at baseline 

 

 Placebo 

(N=587) 

ibandronic acid 2.5 mg daily 

(N=575) 

Relative Risk Reduction 

New morphometric vertebral 

fractures 

 59% (34.5, 74.3) 

Incidence of new morphometric 

vertebral fractures 

12.54% (9.53, 15.55) 5.36% (3.31, 7.41) 

Relative risk reduction of clinical 

vertebral fracture 

 50% (9.49, 71.91) 

Incidence of clinical vertebral 

fracture 

6.97% (4.67, 9.27) 3.57% (1.89, 5.24) 

BMD – mean change relative to 

baseline lumbar spine at year 3 

1.13% (0.6, 1.7) 7.01% (6.5, 7.6) 

BMD – mean change relative to 

baseline total hip at year 3 

-0.70% (-1.1, -0.2) 3.59% (3.1, 4.1) 

 

In the overall patient population of the study MF4411, no reduction was observed for non-vertebral 

fractures, however daily ibandronic acid appeared to be effective in a high-risk subpopulation (femoral 

neck BMD T-score < -3.0), where a non-vertebral fracture risk reduction of 69% was observed. 

 

Daily oral treatment with ibandronic acid 2.5 mg tablets resulted in progressive increases in BMD at 

vertebral and nonvertebral sites of the skeleton.  

 

Three-year lumbar spine BMD increase compared to placebo was 5.3 % and 6.5 % compared to 

baseline. Increases at the hip compared to baseline were 2.8 % at the femoral neck, 3.4 % at the total 

hip, and 5.5 % at the trochanter. 

 

Biochemical markers of bone turnover (such as urinary CTX and serum Osteocalcin) showed the 

expected pattern of suppression to premenopausal levels and reached maximum suppression within a 

period of 3 - 6 months of using 2.5 mg ibandronic acid daily. 

 



25 

A clinically meaningful reduction of 50 % of biochemical markers of bone resorption was observed as 

early as one month after starting treatment with ibandronic acid 2.5 mg. 

Paediatric population (see section 4.2 and section 5.2).  

Bonviva was not studied in the paediatric population, therefore no efficacy or safety data are available 

for this patient population.  

5.2 Pharmacokinetic properties 

The primary pharmacological effects of ibandronic acid on bone are not directly related to actual 

plasma concentrations, as demonstrated by various studies in animals and humans.  

Plasma concentrations of ibandronic acid increase in a dose-proportional manner after intravenous 

administration of 0.5 mg to 6 mg. 

Absorption 

Not applicable 

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 85 % - 87 % (determined in vitro at therapeutic ibandronic acid concentrations), and 

thus there is a low potential for interaction with other medicinal products due to displacement. 

Biotransformation 

There is no evidence that ibandronic acid is metabolised in animals or humans. 

Elimination 

Ibandronic acid is removed from the circulation via bone absorption (estimated to be 40 – 50 % in 

postmenopausal women) and the remainder is eliminated unchanged by the kidney.  

The range of observed apparent half-lives is broad, the apparent terminal half-life is generally in the 

range of 10 - 72 hours. As the values calculated are largely a function of the duration of study, the 

dose used, and assay sensitivity, the true terminal half-life is likely to be substantially longer, in 

common with other bisphosphonates. Early plasma levels fall quickly, reaching 10 % of the 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 considered to reflect the uptake by bone. 

The secretory pathway appears not to include known acidic or basic transport systems involved in the 

excretion of other active substances.(see section 4.5). 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 clinical situations 

Gender 

Pharmacokinetics of ibandronic acid are similar in men and women. 

Race 

There is no evidence for any clinically relevant inter-ethnic differences between Asians and 

Caucasians in ibandronic acid disposition. There is limited data available on patients of African origin. 



26 

Patients with renal impairment  

Renal clearance of ibandronic acid in patients with various degrees of renal impairment is linearly 

related to creatinine clearance (CLcr).  

 

No dose adjustment is necessary for patients with mild or moderate renal impairment (CLcr equal or 

above 30 ml/min).  

 

Subjects with severe renal impairment (CLcr less than 30 ml/min) receiving daily oral administration 

of 10 mg ibandronic acid for 21 days, had 2 - 3 fold higher plasma concentrations than subjects with 

normal renal function and total clearance of ibandronic acid was 44 ml/min. After intravenous 

administration of 0.5 mg of ibandronic acid, total, renal, and non-renal clearances decreased by 67 %, 

77 % and 50 %, respectively, in subjects with severe renal failure, but there was no reduction in 

tolerability associated with the increase in exposure. Due to the limited clinical experience, Bonviva is 

not recommended in patients with severe renal impairment (see section 4.2 and section 4.4). The 

pharmacokinetics of ibandronic acid in patients with end-stage renal disease was only assessed in a 

small number of patients managed by haemodialysis, therefore, the pharmacokinetics of ibandronic 

acid in the patients not undergoing haemodialysis is unknown. Due to the limited data available, 

ibandronic acid should not be used in all patients with end-stage renal disease. 

 

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, which is not metabolised but is cleared 

by renal excretion and by uptake into bone. Therefore dose adjustment is not necessary in patients 

with hepatic impairment. 

 

Elderly population (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, renal function 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 Bonviva in these age groups.  

 

5.3 Preclinical safety data 

 

Toxic effects, e.g. signs of renal damage, were observed in dogs only at exposures considered 

sufficiently in excess of the maximum human exposure, indicating little relevance to clinical use.  

 

Mutagenicity/Carcinogenicity: 

No indication of carcinogenic potential was observed. Tests for genotoxicity revealed no evidence of 

genetic activity for ibandronic acid. 

 

Reproductive toxicity: 

Specific studies for the 3-monthly dosing regimen have not been performed. In studies with daily i.v. 

dosing regimen, there was no evidence for a direct foetal toxic or teratogenic effect of ibandronic acid 

in rats and rabbits. Body weight gain was decreased in F1 offspring in rats. 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. Other adverse reactions to ibandronic acid in reproductive 

toxicity studies in the rat were those observed with bisphosphonates as a class. They include a 

decreased number of implantation sites, interference with natural delivery (dystocia), and an increase 

in visceral variations (renal pelvis ureter syndrome). 

 

 



27 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Sodium chloride 

Glacial acetic acid 

Sodium acetate trihydrate 

Water for injections 

 

6.2 Incompatibilities 

 

Bonviva solution for injection must not be mixed with calcium-containing solutions or other 

intravenously administered medicinal products. 

 

6.3 Shelf life 

 

2 years. 

 

6.4 Special precautions for storage 

 

This medicinal product does not require any special storage conditions. 

 

6.5 Nature and contents of container 

 

Pre-filled syringes (5 ml) made of colourless type I glass, the grey rubber plunger stopper and tip cap 

are made of fluororesin-laminated butyl rubber, containing 3 ml of solution for injection. 

Packs of 1 pre-filled syringe and 1 injection needle or 4 pre-filled syringes and 4 injection needles. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal 

 

Where the medicinal product is administered into an existing intravenous infusion line, the infusate 

should be restricted to either isotonic saline or 50 mg/ml (5 %) glucose solution. This also applies to 

solutions used to flush butterfly and other devices. 

 

Any unused solution for injection, syringe and injection needle should be disposed of in accordance 

with local requirements. The release of pharmaceuticals in the environment should be minimized. 

 

The following points should be strictly adhered to regarding the use and disposal of syringes and other 

medicinal sharps: 

• Needles and syringes should never be reused. 

• Place all used needles and syringes into a sharps container (puncture-proof disposable 

container). 

• Keep this container out of the reach of children. 

• Placing used sharps containers in the household waste should be avoided. 

• Dispose of the full container according to local requirements or as instructed by your 

healthcare professional. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Atnahs Pharma Netherlands B.V. 

Copenhagen Towers,  

Ørestads Boulevard 108, 5.tv 

DK-2300 København S  

Denmark 



28 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/03/265/005 

EU/1/03/265/006 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 23 February 2004 

Date of latest renewal: 18 December 2013 

 

 

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. 

 



29 

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



30 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

Name and address of the manufacturer responsible for batch release 

Film-coated tablet: 

Waymade PLC 

Sovereign House, 

Miles Gray Road, 

Basildon, Essex, SS14 3FR 

United Kingdom 

Waymade PLC 

Josselin Road 

Burnt Mills Industrial Estate 

Basildon 

SS13 1QF 

United Kingdom 

IL CSM Clinical Supplies Management GmbH 

Marie-Curie-Strasse 8 

Lörrach 

Baden-Württemberg 

79539, Germany 

Atnahs Pharma Denmark ApS, 

Copenhagen Towers,  

Ørestads Boulevard 108, 5.tv 

DK-2300 København S  

Denmark 

Solution for injection in pre-filled syringe: 

Waymade PLC 

Sovereign House, 

Miles Gray Road, 

Basildon, Essex, SS14 3FR 

United Kingdom 

Waymade PLC 

Josselin Road 

Burnt Mills Industrial Estate 

Basildon 

SS13 1QF 

United Kingdom 

Atnahs Pharma Denmark ApS, 

Copenhagen Towers,  

Ørestads Boulevard 108, 5.tv 

DK-2300 København S 

Denmark 

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



31 

Medicinal product subject to medical prescription. 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING

AUTHORISATION

• Periodic Safety Update Reports

The requirements for submission of periodic safety update reports for this medicinal product are set 

out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 

2001/83/EC and any subsequent updates 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: 

• 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 minisation) milestone being reached.

Additional risk minimisation measures  

The MAH shall ensure that a patient reminder card regarding osteonecrosis of the jaw is implemented. 

.



32 

ANNEX III 

LABELLING AND PACKAGE LEAFLET 



33 

A. LABELLING



34 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

OUTER CARTON 

1. NAME OF THE MEDICINAL PRODUCT

Bonviva 150 mg film-coated tablets 

Ibandronic acid 

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each film-coated tablet contains 150 mg ibandronic acid (as sodium monohydrate). 

3. LIST OF EXCIPIENTS

The tablets also contain lactose. See the package leaflet for further information. 

4. PHARMACEUTICAL FORM AND CONTENTS

Film-coated tablets 

1 film-coated tablet 

3 film-coated tablets 

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Do not suck, chew or crush tablets 

Read the package leaflet before use 

Once monthly tablet 

Oral use 

Month 1 __/__/__  3 film-coated tablets 

Month 2 __/__/__  3 film-coated tablets 

Month 3 __/__/__  3 film-coated tablets 

Note down the date you take your tablet 

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 



35 

9. SPECIAL STORAGE CONDITIONS

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

Atnahs Pharma Netherlands B.V. 

Copenhagen Towers,  

Ørestads Boulevard 108, 5.tv 

DK-2300 København S  

Denmark 

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/03/265/003 1 film-coated tablet 

EU/1/03/265/004 3 film-coated tablets 

13. BATCH NUMBER

Batch 

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription 

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Bonviva 150 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included. 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: 

SN: 

NN: 



36 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

Blister foil 

1. NAME OF THE MEDICINAL PRODUCT

Bonviva 150 mg film-coated tablets 

Ibandronic acid 

2. NAME OF THE MARKETING AUTHORISATION HOLDER

Atnahs Pharma Netherlands B.V. 

3. EXPIRY DATE

EXP 

4. BATCH NUMBER

Lot 

5. OTHER



37 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

OUTER CARTON  

1. NAME OF THE MEDICINAL PRODUCT

Bonviva 3 mg solution for injection 

Ibandronic acid 

2. STATEMENT OF ACTIVE SUBSTANCE(S)

One pre-filled syringe of 3 ml solution contains 3 mg of ibandronic acid (as sodium monohydrate). 

3. LIST OF EXCIPIENTS

Also contains sodium chloride, glacial acetic acid, sodium acetate trihydrate, water for injections. See 

the package leaflet for further information. 

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection 

1 pre-filled syringe + 1 injection needle 

4 pre-filled syringes + 4 injection needles 

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use 

For intravenous use only 

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



38 

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

Atnahs Pharma Netherlands B.V. 

Copenhagen Towers,  

Ørestads Boulevard 108, 5.tv 

DK-2300 København S  

Denmark 

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/03/265/005 1 pre-filled syringe 

EU/1/03/265/006 4 pre-filled syringes 

13. BATCH NUMBER

Batch 

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription 

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

[Justification for not including Braille accepted] 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included. 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: 

SN: 

NN: 



39 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

PRE-FILLED SYRINGE 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Bonviva 3 mg solution for injection 

Ibandronic acid 

For IV use only 

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

3 mg/3 ml 

6. OTHER



40 

B. PACKAGE LEAFLET



41 

Package leaflet: Information for the user 

 

Bonviva 

150 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 Bonviva is and what it is used for 

2. What you need to know before you take Bonviva 

3. How to take Bonviva 

4. Possible side effects 

5. How to store Bonviva 

6. Content of the pack and other information 

 

 

1. What Bonviva is and what it is used for 

 

Bonviva belongs to a group of medicines called bisphosphonates. It contains the active substance 

ibandronic acid. Bonviva may reverse bone loss by stopping more loss of bone and increasing bone 

mass in most women who take it, even though they won’t be able to see or feel a difference. Bonviva 

may help lower the chances of breaking bones (fractures). This reduction in fractures was shown for 

the spine but not for the hip. 

 

Bonviva is prescribed to you to treat postmenopausal osteoporosis because you have an 

increased risk of fractures. Osteoporosis is a thinning and weakening of the bones, which is common 

in women after the menopause. At the menopause, a woman’s ovaries stop producing the female 

hormone, oestrogen, which helps to keep her skeleton healthy. 

 

The earlier a woman reaches the menopause, the greater her risk of fractures in osteoporosis.  

 

Other things that can increase the risk of fractures include: 

• not enough calcium and vitamin D in the diet 

• smoking, or drinking too much alcohol 

• not enough walking or other weight-bearing exercise 

• a family history of osteoporosis. 

 

A healthy lifestyle will also help you to get the most benefit from your treatment. This includes:  

• eating a balanced diet rich in calcium and vitamin D  

• walking or any other weight-bearing exercise  

• not smoking; and not drinking too much alcohol. 

 

 



42 

2. What you need to know before you take Bonviva 

 

Do not take Bonviva 

• If you are allergic to ibandronic acid, or any of the other ingredients of this medicine listed in 

section 6. 

• If you have certain problems with your gullet/food pipe (oesophagus) such as narrowing or 

difficulty swallowing. 

• If you can’t stand or sit upright for at least one hour (60 minutes) at a time. 

• If you have, or had in the past low blood calcium. Please consult your doctor. 

 

Warnings and precautions 

A side effect called osteonecrosis of the jaw (ONJ) (bone damage in the jaw) has been reported very 

rarely in the post marketing setting in patients receiving Bonviva for osteoporosis.  ONJ can also occur 

after stopping treatment.  

 

It is important to try and prevent ONJ developing as it is a painful condition that can be difficult to 

treat. In order to reduce the risk of developing osteonecrosis of the jaw, there are some precautions 

you should take. 

 

Before receiving treatment, tell your doctor/nurse (health care professional) if: 

• you have any problems with your mouth or teeth such as poor dental health, gum disease, or a 

planned tooth extraction 

• you don’t receive routine dental care or have not had a dental check up for a long time 

• you are a smoker (as this may increase the risk of dental problems) 

• you have previously been treated with a bisphosphonate (used to treat or prevent bone 

disorders) 

• you are taking medicines called corticosteroids (such as prednisolone or dexamethasone) 

• you have cancer. 

 

Your doctor may ask you to undergo a dental examination before starting treatment with Bonviva. 

 

While being treated, you should maintain good oral hygiene (including regular teeth brushing) and 

receive routine dental check-ups. If you wear dentures you should make sure these fit properly. If you 

are under dental treatment or will undergo dental surgery (e.g. tooth extractions), inform your doctor 

about your dental treatment and tell your dentist that you are being treated with Bonviva. 

 

Contact your doctor and dentist immediately if you experience any problems with your mouth or teeth 

such as loose teeth, pain or swelling, or non-healing of sores or discharge, as these could be signs of 

osteonecrosis of the jaw. 

 

Some people need to be especially careful while they’re taking Bonviva. Talk to your doctor before 

taking Bonviva: 

• If you have any disturbances of mineral metabolism (such as vitamin D deficiency).  

• If your kidneys are not functioning normally. 

• If you have any swallowing or digestive problems. 

 

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 Bonviva. If you develop these symptoms, stop taking Bonviva and tell your doctor straight 

away (see section 3). 

 

Children and adolescents 

Do not give Bonviva to children or adolescents below 18 years. 

 



43 

Other medicines and Bonviva 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. Especially: 

 

• Supplements containing calcium, magnesium, iron or aluminium, as they could possibly 

influence the effects of Bonviva. 

 

• Acetylsalicylic acid and other non-steroidal anti-inflammatory medicines (NSAIDs) (including 

ibuprofen, diclofenac sodium and naproxen) may irritate the stomach and intestine. Bonviva 

may also do so. So be especially careful if you take painkillers or anti-inflammatories while 

you’re taking Bonviva.  

 

After swallowing your monthly Bonviva tablet, wait for 1 hour before taking any other medication, 

including indigestion tablets, calcium supplements, or vitamins. 

 

Bonviva with food and drink: 

Do not take Bonviva with food. Bonviva is less effective if it’s taken with food. 

You can drink water but no other drinks  

 

After you have taken Bonviva, please wait for 1 hour before you can have your first food and further 

drinks. (see 3. How to take Bonviva). 

 

Pregnancy and breast feeding 

Bonviva is for use only by postmenopausal women and must not be taken by women who could still 

have a baby.  

Do not take Bonviva if you are pregnant or 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 Bonviva has no or negligible effect on your 

ability to drive and use machines. 

 

Bonviva 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 Bonviva 

 

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 

if you are not sure. 

 

The usual dose of Bonviva is one tablet once a month. 

 

Taking your monthly tablet 

It’s important to follow these instructions carefully. They are designed to help your Bonviva tablet 

reach your stomach quickly, so it’s less likely to cause irritation. 

 

• Take one Bonviva 150 mg tablet once a month. 

• Choose one day of the month that will be easy to remember. You can choose either the same 

date (such as the 1st of each month) or the same day (such as the first Sunday of each month) to 

take your Bonviva tablet. Choose the date that best fits your routine. 

• Take your Bonviva tablet at least 6 hours after you last had anything to eat or drink except 

water. 

 



44 

• Take your Bonviva tablet 

• after you first get up for the day, and 

• before you have anything to eat or drink (on an empty stomach). 

 

• Swallow your tablet with a full glass of water (at least 180 ml).  

 

Do not take your tablet with water with a high concentration of calcium, fruit juice or any other 

drinks. If there is a 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. 

 

• Swallow your tablet whole, do not chew it, crush it or let it dissolve in your mouth. 

 

• For the next hour (60 minutes) after you’ve taken your tablet 

• do not lie down; if you do not stay upright (standing or sitting), some of the medicine 

could leak back into your oesophagus 

 

• do not eat anything 

 

• do not drink anything (except water if you need it) 

• do not take any other medicines. 

 

• After you’ve waited for an hour, you can have your first food and drink of the day. Once you’ve 

eaten, it’s OK to lie down if you wish, and to take any other medication you need. 

 

Continuing to take Bonviva 

It’s important to keep taking Bonviva every month, as long as your doctor prescribes it for you. After 

5 years of  using Bonviva, please consult with your doctor whether you should continue to take 

Bonviva. 

 

If you take more Bonviva than you should 

If you’ve taken more than one tablet by mistake, drink a full glass of milk and talk to your doctor 

straight away. 

 

Do not make yourself vomit, and do not lie down — this could cause Bonviva to irritate your 

oesophagus. 

 

If you forget to take Bonviva 

 

• If you forget to take your tablet on the morning of your chosen day, do not take a tablet later 

in the day.  

Instead, consult your calendar and find out when your next scheduled dose is. 

 



45 

• If you forgot to take your tablet on your chosen day and your next scheduled dose is only 1 

to 7 days away… 

 

Never take two Bonviva tablets within the same week. You should wait until the next 

scheduled dose is due and take it as normal; then, continue taking one tablet once a month on 

the scheduled days you’ve marked on your calendar.  

 

• If you forgot to take your tablet on your chosen day and your next scheduled dose is more 

than 7 days away…  

You should take one tablet the next morning after the day you remember; then, continue taking 

one tablet once a month on the scheduled days you’ve marked on your calendar. 

 

 

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: 

 

Uncommon (may affect up to 1 in 100 people): 

• severe pain in the chest, severe pain after swallowing food or drink, severe nausea, or vomiting, 

difficulty in swallowing. You may have a severe inflammation of  your gullet/food pipe,  

possibly with sores or constriction of the gullet/food pipe. 

 

Rare (may affect up to 1 in 1000 people): 

• itching, swelling of your face, lips, tongue and throat, with difficulty breathing 

• 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) 

• Talk to your doctor if you have ear pain, discharge from the ear, and/or an ear infection. These 

could be signs of bone damage in the ear 

• serious, potentially life-threatening allergic reaction 

• severe adverse skin reactions. 

 

Other possible side effects 

 

Common (may affect up to 1 in 10 people):  

• headache 

• heartburn, discomfort in swallowing, stomach or tummy pain (may be due to an inflammation of 

the stomach), indigestion, nausea, having diarrhoea (loose bowels)  

• muscle cramps, stiffness of your joints and limbs  

• flu-like symptoms, including fever, shaking and shivering, feeling of discomfort, bone pain and 

aching muscles and joints. Talk to a nurse or doctor if any effects become troublesome or last 

more than a couple of days 

• rash. 

 

Uncommon (may affect up to 1 in 100 people): 

• dizziness 

• flatulence (farting, feeling bloated) 

• back pain 

• feeling tired and exhausted 



46 

• asthma attacks. 

 

Rare (may affect up to 1 in 1000 people): 

• inflammation of the duodenum (first section of the bowel) causing stomach pain 

• hives. 

 

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 Bonviva 

 

Keep this medicine out of the sight and reach of children. 

 

There are no special storage instructions. 

 

Do not use this medicine after the expiry date which is stated on the carton after “EXP”. The expiry 

date refers to the last day of that month. 

 

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 Bonviva contains 

 

• The active substance is ibandronic acid. One tablet contains 150 mg of ibandronic acid (as 

sodium monohydrate). 

• The other ingredients are: 

 

tablet core: lactose monohydrate, povidone, cellulose microcrystalline, crospovidone, stearic acid 

purified, silica colloidal anhydrous 

 

tablet coat: hypromellose, titanium dioxide (E 171), talc, macrogol 6000 

 

What Bonviva looks like and contents of the pack 

 

Bonviva tablets are white to off white, of oblong shape and marked “BNVA” on one side, and “150” 

on the other side. The tablets are supplied in blisters containing 1 or 3 tablets. 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder and Manufacturer 

 

Marketing Authorisation Holder 

Atnahs Pharma Netherlands B.V. 

Copenhagen Towers,  

Ørestads Boulevard 108, 5.tv 

DK-2300 København S  

Denmark 

 

Manufacturer 

Waymade PLC 

Sovereign House, 

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


47 

Miles Gray Road, 

Basildon, Essex, SS14 3FR 

United Kingdom 

 

Waymade PLC 

Josselin Road 

Burnt Mills Industrial Estate 

Basildon 

SS13 1QF 

United Kingdom 

 

IL CSM Clinical Supplies Management GmbH 

Marie-Curie-Strasse 8 

Lörrach 

Baden-Württemberg 

79539, Germany 

 

Atnahs Pharma Denmark ApS, 

Copenhagen Towers,  

Ørestads Boulevard 108, 5.tv 

DK-2300 København S 

Denmark 

 

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. 

 

 



48 

 

 

 

PLANNING WHEN TO TAKE BONVIVA 

 

The dose of Bonviva is one tablet once a month. Choose one day of the month that will be easy to 

remember: 

• either the same date (such as the 1st of each month)  

• or the same day (such as the first Sunday of each month).  

 

 

It’s important to keep taking Bonviva every month.  



49 

  

Package leaflet: Information for the user 

 

Bonviva 3 mg solution for injection  

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 Bonviva is and what it is used for 

2. What you need to know before you receive Bonviva  

3. How to receive Bonviva  

4. Possible side effects 

5. How to store Bonviva  

6. Content of the pack and other information 

 

 

1. What Bonviva is and what it is used for 

 

Bonviva belongs to a group of medicines called bisphosphonates. It contains the active substance 

ibandronic acid.  

Bonviva may reverse bone loss by stopping more loss of bone and increasing bone mass in most 

women who take it, even though they won’t be able to see or feel a difference. Bonviva  may help 

lower the chances of breaking bones (fractures). This reduction in fractures was shown for the spine 

but not for the hip. 

 

Bonviva is prescribed to you to treat postmenopausal osteoporosis because you have an 

increased risk of fractures. Osteoporosis is a thinning and weakening of the bones, which is common 

in women after the menopause. At the menopause, a woman’s ovaries stop producing the female 

hormone, oestrogen, which helps to keep her skeleton healthy. The earlier a woman reaches the 

menopause, the greater her risk of fractures in osteoporosis. 

 

Other things that can increase the risk of fractures include: 

• not enough calcium and vitamin D in the diet 

• smoking cigarettes, or drinking too much alcohol 

• not enough walking or other weight-bearing exercise 

• a family history of osteoporosis. 

 

A healthy lifestyle will also help you to get the most benefit from your treatment. This includes: 

• eating a balanced diet rich in calcium and vitamin D  

• walking or other weight-bearing exercise 

• not smoking and not drinking too much alcohol.  

 

 

2. What you need to know before you receive Bonviva  

 

Do not receive Bonviva 

• if you have, or had in the past, low blood calcium. Please consult your doctor 

• if you are allergic to ibandronic acid or any of the other ingredients of this medicine (listed in 

section 6). 

 



50 

Warnings and precautions 

A side effect called osteonecrosis of the jaw (ONJ) (bone damage in the jaw) has been reported very 

rarely in the post marketing setting in patients receiving Bonviva for osteoporosis.  ONJ can also occur 

after stopping treatment.  

 

It is important to try and prevent ONJ developing as it is a painful condition that can be difficult to 

treat. In order to reduce the risk of developing osteonecrosis of the jaw, there are some precautions 

you should take. 

 

Before receiving treatment, tell your doctor/nurse (health care professional) if: 

• you have any problems with your mouth or teeth such as poor dental health, gum disease, or a 

planned tooth extraction 

• you don’t receive routine dental care or have not had a dental check up for a long time 

• you are a smoker (as this may increase the risk of dental problems) 

• you have previously been treated with a bisphosphonate (used to treat or prevent bone 

disorders) 

• you are taking medicines called corticosteroids (such as prednisolone or dexamethasone) 

• you have cancer. 

 

Your doctor may ask you to undergo a dental examination before starting treatment with Bonviva. 

 

While being treated, you should maintain good oral hygiene (including regular teeth brushing) and 

receive routine dental check-ups.  If you wear dentures you should make sure these fit properly. If you 

are under dental treatment or will undergo dental surgery (e.g. tooth extractions), inform your doctor 

about your dental treatment and tell your dentist that you are being treated with Bonviva. 

 

Contact your doctor and dentist immediately if you experience any problems with your mouth or teeth 

such as loose teeth, pain or swelling, or non-healing of sores or discharge, as these could be signs of 

osteonecrosis of the jaw. 

 

Some patients need to be especially careful when using Bonviva. Talk to your doctor before receiving 

Bonviva: 

• If you have or have ever had kidney problems, kidney failure or have needed dialysis, or if you 

have any other disease that may affect your kidneys  

• If you have any disturbance of mineral metabolism (such as vitamin D deficiency) 

• You should take calcium and vitamin-D supplements while receiving Bonviva. If you are 

 unable to do so, you should inform your doctor 

 

• If you have heart problems and the doctor recommended to limit your daily fluid intake. 

 

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  

Bonviva must not be used in children or adolescents below 18 years. 

 

Other medicines and Bonviva 

Tell your doctor, nurse or pharmacist if you are taking, have recently taken or might take any other 

medicines. 

 

Pregnancy and breast-feeding 

Bonviva is for use only by postmenopausal women and must not be taken by women who could still 

have a baby.  

Do not take Bonviva if you are pregnant or breast-feeding.  



51 

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 Bonviva has no or negligible effect on your 

ability to drive and use machines.  

 

Bonviva contains less than 1 mmol sodium (23 mg) per dose (3 ml), i.e. essentially “sodium-free”. 

 

 

3. How to receive Bonviva  

 

The recommended dose of Bonviva for the intravenous injection is 3 mg (1 pre-filled syringe) once 

every 3 months. 

 

The injection should be given into the vein by a physician or qualified/trained health care worker. Do 

not administer the injection to yourself. 

 

The solution for injection must be administered into a vein only, and not anywhere else in the body. 

 

Continuing to receive Bonviva 

To get the most benefit from the treatment it is important to continue receiving the injections every 3 

months for as long as your doctor prescribes it for you. Bonviva can treat osteoporosis only for as long 

as you keep receiving the treatment, even though you will not be able to see or feel a difference. After 

5 years of receiving Bonviva, please consult with your doctor whether you should continue to receive 

Bonviva. 

 

You should also take calcium and vitamin-D supplements, as recommended by your doctor. 

 

If too much Bonviva is given 

You may develop low levels of calcium, phosphorus or magnesium in the blood. Your doctor may 

take steps to correct such changes and may give you an injection containing these minerals. 

 

If a dose of Bonviva is missed 

You should arrange an appointment to get the next injection as soon as possible. After that, go back to 

getting the injections every 3 months from the date of the most recent injection.  

 

 

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: 

 

Rare (may affect up to 1 in 1000 people): 

• itching, swelling of your face, lips, tongue and throat, with difficulty breathing  

• persistent eye pain and inflammation (if prolonged) 

• 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 10000 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) 

• Talk to your doctor if you have ear pain, discharge from the ear, and/or an ear infection. These 

could be signs of bone damage in the ear 

• serious, potentially life-threatening allergic reaction (see section 2) 

• severe adverse skin reactions. 



52 

 

Other possible side effects 

 

Common (may affect up to 1 in 10 people):  

• headache 

• stomach pain (such as gastritis) or tummy pain, indigestion, nausea, having diarrhoea (loose 

bowels) or constipation 

• pain in your muscles, joints, or back 

• feeling tired and exhausted 

• flu-like symptoms, including fever, shaking and shivering, feeling of discomfort, bone pain and 

aching muscles and joints. Talk to a nurse or doctor if any effects become troublesome or last 

more than a couple of days 

• rash.  
 

Uncommon (may affect up to 1 in 100 people) 

• inflammation of a vein  

• pain or injury at the injection site 

• bone pain 

• feeling weak 

• asthma attacks. 

 

Rare (may affect up to 1 in 1000 people): 

• hives. 

 

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 Bonviva  

 

Keep this medicine out of the sight and reach of children. 

 

This medicinal product does not require any special storage conditions. 

 

Do not use Bonviva this medicine after the expiry date which is stated on the carton and on the syringe 

after “EXP”. The expiry date refers to the last day of that month. 

 

The person giving the injection should throw away any unused solution and put the used syringe and 

injection needle into an appropriate disposal container. 

 

 

6. Content of the pack and other information 

 

What Bonviva contains 

 

• The active substance is ibandronic acid. One pre-filled syringe contains 3 mg of ibandronic acid 

in 3 ml of solution (as sodium monohydrate). 

• The other ingredients are sodium chloride, acetic acid, sodium acetate trihydrate and water for 

injections. 

 

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


53 

What Bonviva looks like and contents of the pack 

 

Bonviva 3 mg solution for injection in pre-filled syringes is a clear colourless solution. Each pre-filled 

syringe contains 3 ml of solution. Bonviva is available in packs of 1 pre-filled syringe and 1 injection 

needle or 4 pre-filled syringes and 4 injection needles.  

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder and Manufacturer 

 

Marketing Authorisation Holder 

Atnahs Pharma Netherlands B.V. 

Copenhagen Towers,  

Ørestads Boulevard 108, 5.tv 

DK-2300 København S  

Denmark 

 

Manufacturer 

Waymade PLC 

Sovereign House, 

Miles Gray Road, 

Basildon, Essex, SS14 3FR 

United Kingdom 

 

Waymade PLC 

Josselin Road 

Burnt Mills Industrial Estate 

Basildon 

SS13 1QF 

United Kingdom 

 

Atnahs Pharma Denmark ApS, 

Copenhagen Towers,  

Ørestads Boulevard 108, 5.tv 

DK-2300 København S 

Denmark 

 

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. 



54 

This information is intended for healthcare professionals only: 

 

INFORMATION FOR THE HEALTHCARE PROFESSIONALS 

 

Please see the Summary of Product Characteristics for more information. 

 

Administration of Bonviva 3 mg solution for injection in pre-filled syringe: 

 

Bonviva 3 mg solution for injection in pre-filled syringe should be injected intravenously over a 

period of 15 - 30 seconds. 

 

The solution is irritant, therefore strict adherence to the intravenous route of administration is 

important. If you inadvertently inject into the tissues around the vein, patients may experience local 

irritation, pain and inflammation at the injection site. 

 

Bonviva 3 mg solution for injection in pre-filled syringe must not be mixed with calcium-containing 

solutions (such as Ringer-Lactate solution, calcium heparin) or other intravenously administered 

medicinal products. Where Bonviva is administered via an existing intravenous infusion line, the 

intravenous infusate should be restricted to either isotonic saline or 50 mg/ml (5 %) glucose solution. 

 

Missed dose: 

If a dose is missed, the injection should be administered as soon as convenient. Thereafter, injections 

should be scheduled every 3 months from the date of the last injection. 

 

Overdose: 

No specific information is available on the treatment of overdosage with Bonviva.  

 

Based on knowledge of this class of compounds, intravenous overdosage may result in hypocalcaemia, 

hypophosphataemia, and hypomagnesaemia, which can cause paraesthesia. In severe cases 

intravenous infusion of appropriate doses of calcium gluconate, potassium or sodium phosphate, and 

magnesium sulfate, may be needed. 

 

General advice: 

Bonviva 3 mg solution for injection in pre-filled syringe like other bisphosphonates administered 

intravenously, may cause a transient decrease in serum calcium values. 

 

Hypocalcaemia and other disturbances of bone and mineral metabolism should be assessed and 

effectively treated before starting Bonviva injection therapy. Adequate intake of calcium and 

vitamin D is important in all patients. All patients must receive supplemental calcium and vitamin D. 

 

Patients with concomitant diseases, or who use medicinal products which have a potential for 

undesirable effects on the kidney, should be reviewed regularly in line with good medical practice 

during treatment.  

 

Any unused solution for injection, syringe and injection needle should be disposed of in accordance 

with local requirements. 

 


	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 MARKETINGAUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET