Last Updated on eMC 05-05-2016 View medicine  | Roche Products Limited Contact details

When a pharmaceutical company changes an SPC or PIL, a new version is published on the eMC.  For each version, we show the dates it was published on the eMC and the reasons for change.

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:21-04-2016

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Underlined text = new text

Strikethrough text = deleted text

 

 

4.2     Posology and method of administration

 

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

 

[ … ]

 

 

4.4     Special warnings and precautions for use

 

[ … ]

 

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 jaw, generally associated with tooth extraction and/or local infection (including osteomyelitis) has been reported in patients with cancer receiving treatment regimens including primarily intravenously administered bisphosphonates. Many of these patients were also receiving chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in patients with osteoporosis receiving oral bisphosphonates.

 

A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, radiotherapy, corticosteroids, poor oral hygiene).

 

While on treatment, these patients should avoid invasive dental procedures if possible. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. Clinical judgement of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.

 

Osteonecrosis of the external auditory canal

Osteonecrosis of the external auditory canal has been reported with bisphosphonates, mainly in association with long-term therapy. Possible risk factors for osteonecrosis of the external auditory canal include steroid use and chemotherapy and/or local risk factors such as infection or trauma. The possibility of osteonecrosis of the external auditory canal should be considered in patients receiving bisphosphonates who present with ear symptoms including chronic ear infections.

 

[ … ]

 

4.8     Undesirable effects

 

[ … ]

 

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

 

[ … ]

 

 

 

 

 

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)†

[ … ]

 

 

 

 

 

*See further information below

†Identified in post-marketing experience.

 

[ … ]

 

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.Osteonecrosis of the jaw has been reported in patients treated by bisphosphonates. The majority of the reports refer to cancer patients, but such cases have also been reported in patients treated for osteoporosis. Osteonecrosis of the jaw is generally associated with tooth extraction and/or local infection (including osteomyelitis). Diagnosis of cancer, chemotherapy, radiotherapy, corticosteroids and poor oral hygiene are also deemed as risk factors (see section 4.4).

 

[ … ]

 

 

10.     DATE OF REVISION OF THE TEXT

 

21 April 2016

 

 

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:28-05-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 4.8 - Undesirable effects

Stevens-Johnson Syndrome, Erythema Multiforme, Dermatitis Bullous added as very rare Skin and subcutaneous tissues disorders

Section 10 - DATE OF REVISION OF THE TEXT

Updated to 28 May 2015

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.6 - Fertility, pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 9 - Date of first authorisation/renewal of the authorisation
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:18-12-2013

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Underlined text = new text
Strike through text = deleted text

4.2     Posology and method of administration

 

[ … ]

 

Method of administration

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

 

[ … ]


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.

 

[ … ]


4.8     Undesirable effects

 

Summary of the safety profile

The safety profile of Bonviva is derived from controlled clinical trials and post-marketing experience  The most serious reported adverse reactions are anaphylactic reaction/shock, atypical fractures of the femur, osteonecrosis for the jaw and ocular inflammation (see paragraph “Description of selected adverse reactions” and section 4.4).

The most frequently reported adverse reactions were 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 an a complete list overview 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).


[ … ]


Adverse reactions are listed according to MedDRA system organ class and frequency category. Frequency categories are defined using the following convention: very common (>1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.


Table 1: Adverse  reactions 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.

 

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.

 

 

System Organ Class

Common

Uncommon

Rare

Very rare

Immune system disorders

 

Asthma exacerbation

Hypersensitivity reaction

Anaphylactic reaction/shock*

 

 

[ … ]

 

 

 

 

 


[ … ]


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 (see details below) via the national reporting system listed in Appendix V.


Ireland

Pharmacovigilance Section

Irish Medicines Board

Kevin O’Malley House

Earlsfort Centre

Earlsfort Terrace

IRL - Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.imb.ie

e-mail: imbpharmacovigilance@imb.ie

 

Malta

ADR Reporting

The Medicines Authority

Post-Licensing Directorate

203 Level 3, Rue D'Argens

GŻR-1368 Gżira

Website: www.medicinesauthority.gov.mt

e-mail: postlicensing.medicinesauthority@gov.mt

 

United Kingdom

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

 

6.6       Special precautions for disposal

 

[ … ]

 

·     Dispose of the full container according to local requirements or as instructed by your healthcare providerprofessional.

 

 9.       DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

 

Date of first authorisation: 23.02.2004

Date of latest renewal: 18.12.201323.02.2009

 

 10.     DATE OF REVISION OF THE TEXT

18 December 2013

 

[ … ]

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Fertility, pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 9 - Date of first authorisation/renewal of the authorisation
  • Change to section 10 - Date of revision of the text
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications

Date of revision of text on the SPC:15-11-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Underline text = new text
Struck through text = deleted text

2.       QUALITATIVE AND QUANTITATIVE COMPOSITION

 

One pre-filled syringe of 3 ml solution contains 3 mg ibandronic acid (as 3.375 mg ibandronic acid, monosodium salt,sodium monohydrate).

The concentration of ibandronic acid in the solution for injection is 1 mg1mg per ml.

 

Excipients: Sodium (less than 1 mmol per dose).

 

For athe full list of excipients, see section 6.1.

 

[ … ]

 

4.2     Posology and method of administration

 

[ … ]

 

Special populations

Patients with renal impairment

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.

 

[ … ]

 

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.

 

[ … ]

 

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 the paediatricthis population . (see section 5.1 and 5.2).

 

[ … ]

 

4.3     Contraindications

 

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

 

[ … ]

 

4.4     Special warnings and precautions for use

 

[ … ]

 

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.

 

Atypical fractures of the femur

Atypical subtrochanteric and diaphyseal femoral fractures have been reported with bisphosphonate therapy, primarily in patients receiving long-term treatment for osteoporosis. These transverse or short oblique fractures can occur anywhere along the femur from just below the lesser trochanter to just above the supracondylar flare. These fractures occur after minimal or no trauma and some patients experience thigh or groin pain, often associated with imaging features of stress fractures, weeks to months before presenting with a completed femoral fracture. Fractures are often bilateral; therefore the contralateral femur should be examined in bisphosphonate-treated patients who have sustained a femoral shaft fracture. Poor healing of these fractures has also been reported. Discontinuation of bisphosphonate therapy in patients suspected to have an atypical femur fracture should be considered pending evaluation of the patient, based on an individual benefit risk assessment.

During bisphosphonate treatment patients should be advised to report any thigh, hip or groin pain and any patient presenting with such symptoms should be evaluated for an incomplete femur fracture.

 

[ … ]

 

Patients with cardiac impairment

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

 

[ … ]

 

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. Furthermore, plasma protein binding 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. (see section 5.2). Ibandronic acid is eliminated by renal excretion only and does not undergo any biotransformation. The secretory pathway appears not to include known acidic or basic transport systems involved in the excretion of other active substances.

 

Pharmacokinetic interaction studies in postmenopausal women have demonstrated the absence of any interaction potential with tamoxifen or hormone replacement therapy (oestrogen).

 

No interaction was observed when co-administered with melphalan/prednisolone in patients with multiple myeloma.

 

4.6     Fertility, pregnancy and lactation

 

[ … ]

 

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 lactation breastfeeding.

 

[ … ]

 

4.7     Effects on ability to drive and use machines

 

No studies onOn the effectsbasis 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 have been performed..

 

4.8     Undesirable effects

 

Summary of the safety profile

The safety profile of Bonviva is derived from controlled clinical trials and post marketingpost-marketing experience  . The most frequently reported adverse reactions were 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 an overview of 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). The overall safety profile of ibandronic acid 2.5 mg daily in all these studies was similar to that of placebo.

 

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. The majority of adverse reactions were mild to moderate in intensity. Most cases of adverse reactions did not lead to cessation of therapy.

 

The most commonly reported adverse reaction was influenza like illness.

 

Adverse reactions considered by investigators to be causally related to Bonviva are listed below by System Organ Class.

 

Frequencies are defined as common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000) and very rare (<1/10,000). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

 

Table 1: Adverse drug 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 postmarketingpost-marketing experience.

 

Adverse reactions are listed according to MedDRA system organ class and frequency category. Frequency categories are defined using the following convention: very common (>1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000) ,very rare (<1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

 

 

System Organ Class

Common

Uncommon

Rare

Very rare

Immune system disorders

 

 

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

 

Musculoskeletal and , connective tissue and bone disorders

Arthralgia, Myalgia, Musculoskeletal pain, Back pain

Bone pain

Atypical subtrochanteric and diaphyseal femoral fractures (bisphosphonate class adverse reaction)

Osteonecrosis of jaw*

General disorders and administration site conditions

Influenza like illness*, Fatigue

Injection site reactions, Asthenia

 

 

*See further information below

†Identified in postmarketingpost-marketing experience.

 

Description of selected adverse reactions

 

Influenza-like illness

Transient, influenza-like symptoms have been reported in patients receiving intravenous injection of Bonviva 3 mg every 3 months, typically in association with the first dose.of Bonviva

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. Such symptoms were generally of short duration, mild or moderate in intensity, and resolved during continuing treatment without requiring remedial measures.

 

 

Osteonecrosis of the jaw

Osteonecrosis of the jaw has been reported in patients treated by bisphosphonates. The majority of the reports refer to cancer patients, but such cases have also been reported in patients treated for osteoporosis. Osteonecrosis of the jaw is generally associated with tooth extraction and / or local infection (including osteomyelitis). Diagnosis of cancer, chemotherapy, radiotherapy, corticosteroids and poor oral hygiene are also deemed as risk factors (see section 4.4).

 

[ … ]

 

Anaphylactic reaction/shock

Cases of anaphylactic reaction/shock, including fatal events, have been reported in patients treated with intravenous ibandronic acid.

 

[ … ]

 

5.1     Pharmacodynamic properties

 

Pharmacotherapeutic group: DrugsMedicinal products for treatment of bone diseases, bisphosphonates, ATC code: M05BA06

 

[ … ]

 

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 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.

 

[ … ]

 

Patients with hepatic impairment (see section 4.2)

 

[ … ]

 

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.

 

[ … ]

 

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.

 

[ … ]

 

9.       DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

 

Date of first authorisation: 23.02.2004/23

Date of latest renewal: 23.02.2009

 

 

10.     DATE OF REVISION OF THE TEXT

 

15 November 2012

 

[ … ]

 

Reasons for adding or updating:

  • Change to section 4.6 - Pregnancy and Lactation
  • Change to section 5.3 - Preclinical Safety Data

Date of revision of text on the SPC:27-07-2011

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Test underlined has been added:

 

4.6      Fertility, Ppregnancy and lactation

 

Pregnancy

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 lactation.

 

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).

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).

 

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.8 - Undesirable Effects

Date of revision of text on the SPC:29-06-2011

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Underlined text has been added, text with strike through deleted:

4.2      Posology and method of administration

 

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

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.

 

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)

 

Patients with hepatic impairment

No dose adjustment is required (see section 5.2).

 

Elderly population

No dose adjustment is required (see section 5.2).

 

Paediatric population

There is no relevant use of Bonviva in children, and Bonviva was not studied in the paediatric population .

 

Method of administration:

For intravenous use.

 

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

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.

 

Atypical fractures of the femur

Atypical subtrochanteric and diaphyseal femoral fractures have been reported with bisphosphonate therapy, primarily in patients receiving long-term treatment for osteoporosis. These transverse or short oblique fractures can occur anywhere along the femur from just below the lesser trochanter to just above the supracondylar flare. These fractures occur after minimal or no trauma and some patients experience thigh or groin pain, often associated with imaging features of stress fractures, weeks to months before presenting with a completed femoral fracture. Fractures are often bilateral; therefore the contralateral femur should be examined in bisphosphonate-treated patients who have sustained a femoral shaft fracture. Poor healing of these fractures has also been reported. Discontinuation of bisphosphonate therapy in patients suspected to have an atypical femur fracture should be considered pending evaluation of the patient, based on an individual benefit risk assessment.

During bisphosphonate treatment patients should be advised to report any thigh, hip or groin pain and any patient presenting with such symptoms should be evaluated for an incomplete femur fracture.

 

Renal 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).

 

Osteonecrosis of the jaw

Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including osteomyelitis) has been reported in patients with cancer receiving treatment regimens including primarily intravenously administered bisphosphonates. Many of these patients were also receiving chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in patients with osteoporosis receiving oral bisphosphonates.

 

A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, radiotherapy, corticosteroids, poor oral hygiene).

 

While on treatment, these patients should avoid invasive dental procedures if possible. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. Clinical judgement of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.

4.8      Undesirable effects

 

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). The overall safety profile of ibandronic acid 2.5 mg daily in all these studies was similar to that of placebo.

 

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. The majority of adverse reactions were mild to moderate in intensity. Most cases of adverse reactions did not lead to cessation of therapy.

 

The most commonly reported adverse reaction was influenza like illness.

 

Adverse reactions considered by investigators to be causally related to Bonviva are listed below by System Organ Class.

 

Frequencies are defined as common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), and rare (≥ 1/10,000 to < 1/1,000). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

 

Table 1: Adverse drug 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 postmarketing experience.

 

System Organ Class

Common

Uncommon

Rare

Very rare

Immune system disorders

 

 

Hypersensitivity reaction

 

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

 

Musculoskeletal, connective tissue and bone disorders

Arthralgia, Myalgia, Musculoskeletal pain, Back pain

Bone pain

Atypical subtrochanteric and diaphyseal femoral fractures (bisphosphonate class adverse reaction)

Osteonecrosis of jaw*

General disorders and administration site conditions

Influenza like illness*, Fatigue

Injection site reactions, Asthenia

 

 

*See further information below

†Identified in postmarketing experience.

Influenza-like illness

Transient, influenza-like symptoms have been reported in patients receiving intravenous injection of Bonviva 3 mg every 3 months, typically in association with the first dose.

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. Such symptoms were generally of short duration, mild or moderate in intensity, and resolved during continuing treatment without requiring remedial measures.

 

Osteonecrosis of jaw

Osteonecrosis of the jaw has been reported in patients treated by bisphosphonates. The majority of the reports refer to cancer patients, but such cases have also been reported in patients treated for osteoporosis. Osteonecrosis of the jaw is generally associated with tooth extraction and / or local infection (including osteomyelitis). Diagnosis of cancer, chemotherapy, radiotherapy, corticosteroids and poor oral hygiene are also deemed as risk factors (see section 4.4).

 

Ocular inflammation

Ocular inflammation events such as uveitis, episcleritis and scleritis have been reported with ibandronic acid. In some cases, these events did not resolve until the ibandronic acid was discontinued.

 

Reasons for adding or updating:

  • Correction of spelling/typing errors

Date of revision of text on the SPC:14-04-2011

Legal Category:POM

Black Triangle (CHM): NO

Reasons for adding or updating:

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.8 - Undesirable Effects
  • Change to section 5.1 - Pharmacodynamic Properties
  • Change to section 6. 6 - Instructions for use, handling and disposal

Date of revision of text on the SPC:14-04-2011

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Underlined text has been added, text with strike through deleted:

 

2.       QUALITATIVE AND QUANTITATIVE COMPOSITION

 

One pre-filled syringe of 3 ml solution contains 3 mg ibandronic acid (as 3.375 mg ibandronic acid, monosodium salt, monohydrate).

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

 

Excipients: Sodium (less than 1 mmol per dose).

 

For a full list of excipients, see section 6.1.

 

4.3     Contraindications

 

-        Hypocalcaemia (see section 4.4)

-        Hypersensitivity to ibandronic acid or to any of the excipients.

-        Hypocalcaemia

 

4.4     Special warnings and precautions for use

 

[…]

 

Administration failures

Strict adherence to the intravenous route of administration is required. Care must be taken not to administer Bonviva injection via intra-arterial or paravenous administration as this could lead to tissue damage.

 

[…]

 

4.8     Undesirable effects

 

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). The overall safety profile of ibandronic acid 2.5 mg daily in all these studies was similar to that of placebo.

 

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. The majority of adverse reactions were mild to moderate in intensity. Most cases of adverse reactions did not lead to cessation of therapy.

 

The most commonly reported adverse reaction was influenza like illness.

 

Adverse reactions considered by investigators to be causally related to Bonviva are listed below by System Organ Class.

 

Frequencies are defined as common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), and rare (≥ 1/10,000 to < 1/1,000). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

 

Table 1: Adverse drug reactions occurring in postmenopausal women receiving Bonviva 33 mg injection every 3 months or ibandronic acid 2.55 mg daily in the phase III studies BM16550 and MF 4411 and in postmarketing experience.

 

System Organ Class

Frequency

Adverse reactions

Immune system disorders

Rare

Hypersensitivity reaction

Nervous system disorders

Common

Headache

Vascular disorders

Uncommon

Phlebitis/thrombophlebitis

Gastrointestinal disorders

Common

Gastritis, Dyspepsia, Diarrhoea, Abdominal pain, Nausea, Constipation

Skin and subcutaneous tissues disorders

Common

Rash

 

Rare

Angioedema, Facial swelling/oedema, Urticaria

Musculoskeletal, connective tissue and bone disorders

Common

Arthralgia, Myalgia, Musculoskeletal pain, Back pain

 

Uncommon

Bone pain

General disorders and administration site conditions

Common

Influenza like illness*, Fatigue

 

Uncommon

Injection site reactions, Asthenia

MedDRA version 8.0

*

System Organ Class

Common

Uncommon

Rare

Very rare

Immune system disorders

 

 

Hypersensitivity reaction

 

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

 

Musculoskeletal, connective tissue and bone disorders

Arthralgia, Myalgia, Musculoskeletal pain, Back pain

Bone pain

 

Osteonecrosis of jaw*

General disorders and administration site conditions

Influenza like illness*, Fatigue

Injection site reactions, Asthenia

 

 

*See further information below

†Identified in postmarketing experience.

Influenza-like illness

Transient, influenza-like symptoms have been reported in patients receiving intravenous injection of Bonviva 3 mg every 3 months, typically in association with the first dose.

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. Such symptoms were generally of short duration, mild or moderate in intensity, and resolved during continuing treatment without requiring remedial measures.

 

Laboratory test findings

In the pivotal three-year study with oral ibandronic acid 2.5 mg daily (MF 4411) there was no difference compared with placebo for laboratory abnormalities indicative of hepatic or renal dysfunction, impaired haematologic system, hypocalcaemia or hypophosphataemia. Similarly, no differences were noted between the groups in the pivotal study with Bonviva 3 mg injection every 3 months (BM 16550).

 

Post-marketing Experience

Osteonecrosis of jaw

Osteonecrosis of the jaw has been reported in patients treated by bisphosphonates. The majority of the reports refer to cancer patients, but such cases have also been reported in patients treated for osteoporosis. Osteonecrosis of the jaw is generally associated with tooth extraction and / or local infection (including osteomyelitis). Diagnosis of cancer, chemotherapy, radiotherapy, corticosteroids and poor oral hygiene are also deemed as risk factors (see section 4.4).

 

Ocular inflammation

Ocular inflammation events such as uveitis, episcleritis and scleritis have been reported with ibandronic acid. In some cases, these events did not resolve until the ibandronic acid was discontinued.

 

5.1       Pharmacodynamic properties

 

Pharmacotherapeutic group: Drugs for treatment of bone diseases, Bbisphosphonates, ATC code: M05B A06

 

[…]

 

Paediatric population

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

 

[…]

 

6.6       Special precautions for disposal

 

Where the 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 provider

 

Reasons for adding or updating:

  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:08-02-2010

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

change to date of revision of text and updated EMA link

Reasons for adding or updating:

  • Removal of Black Triangle

Date of revision of text on the SPC:02-07-2009

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Removal of the black triangle

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects

Date of revision of text on the SPC:02-07-2009

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



Underlined text has been added, text with strike through deleted:

 

4.8       Undesirable effects

 

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). ; 73 % of these patients came from the pivotal three-year treatment study (MF 4411). The overall safety profile of ibandronic acid 2.5 mg daily in all these studies was similar to that of placebo. The overall proportion of patients who experienced an adverse reaction, i.e. adverse event with a possible or probable relationship to trial medication, in the pivotal treatment study (MF 4411) was 19.8 % for ibandronic acid and 17.9 % for placebo.

 

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 and 21.5 % and 22.5 % for ibandronic acid 2.5 mg daily after one and two years, respectively. The majority of adverse reactions were mild to moderate in intensity. Most cases did not lead to cessation of therapy.

 

The most commonly reported adverse reaction was arthralgia.

 

Table 1 and table 2 list adverse reactions occurring in more than 1 % of patients treated with Bonviva 150 mg monthly or 2.5 mg daily in study BM 16549 and in patients treated with ibandronic acid 2.5 mg daily in study MF 4411. The tables show the adverse reactions in the two studies that occurred with a higher incidence than in patients treated with placebo in study MF 4411. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

 

Data at one year from BM 16549 are represented in Table 1 and cumulative data for the two years from BM 16549 are represented in table 2.

 

Table 1: Common adverse reactions (>1/100, ≤ 1/10) in phase III osteoporosis studies that were considered by the investigator to be possibly or probably related to treatment - One year data from study BM 16549 and three year data from placebo-controlled fracture study MF 4411

 

 

One year data in study BM 16549

Three year data in study MF 4411

System Organ Class/ Adverse reaction

Bonviva 150 mg once monthly

(N=396)

(%)

ibandronic acid 2.5 mg daily

(N=395)

(%)

ibandronic acid 2.5 mg daily

(N=977)

(%)

Placebo

(N=975)

(%)

Gastrointestinal system

 

 

 

 

Gastro-oesophageal reflux disease

0.5

1.0

0.4

0.1

Diarrhoea

2.5

1.8

1.4

1.0

Abdominal pain

3.5

2.8

2.1

2.9

Dyspepsia

3.3

5.8

4.3

2.9

Nausea

3.3

3.5

1.8

2.3

Flatulence

0.5

1.0

0.4

0.7

Nervous system

 

 

 

 

Headache

0.8

1.5

0.8

0.6

General disorders

 

 

 

 

Influenza like illness*

3.3

0.3

0.3

0.2

Fatigue

1.0

0.3

0.3

0.4

Musculoskeletal system

 

 

 

 

Arthralgia

1.0

0.3

0.4

0.4

Myalgia

1.5

0.3

1.8

0.8

Skin disorders

 

 

 

 

Rash

0.8

1.0

1.2

0.7

MedDRA version 6.1

* Transient, influenza-like symptoms have been reported with Bonviva 150 mg once monthly, typically in association with the first dose. Such symptoms were generally of short duration, mild or moderate in intensity, and resolved during continuing treatment without requiring remedial measures. 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.

 

Table 2: Cumulative common adverse reactions (>1/100, ≤ 1/10) in Phase III osteoporosis studies  that were considered by the investigator to be possibly or probably related to treatment - Two year data from study BM 16549 and three year data from placebo-controlled fracture study MF 4411

 

 

Two year cumulative data in study BM 16549

Three year data in study MF 4411

System Organ Class/ Adverse reaction

Bonviva 150 mg once monthly

(N=396)

(%)

ibandronic acid 2.5 mg daily

(N=395)

(%)

ibandronic acid 2.5 mg daily

(N=977)

(%)

Placebo

(N=975)

(%)

Gastrointestinal system

 

 

 

 

Gastritis

1.0

0.3

0.7

0.5

Gastro-oesophageal reflux disease

0.8

1.0

0.5

0.1

Oesophagitis

0

1.0

0.5

0.4

Diarrhoea

2.5

2.0

1.4

1.0

Abdominal pain

4.0

3.0

2.1

2.9

Dyspepsia

4.0

6.3

4.0

2.7

Nausea

3.0

3.5

1.8

2.3

Nervous system

 

 

 

 

Headache

0.8

1.5

0.8

0.6

General disorders

 

 

 

 

Influenza like illness*

3.3

0.3

0.3

0.2

Musculoskeletal system

 

 

 

 

Muscle cramp

0.5

1.0

0.1

0.4

Musculoskeletal pain

1.0

0.5

0

0

Arthralgia

1.0

0.5

0.4

0.4

Myalgia

1.5

0.3

1.8

0.8

Musculoskeletal stiffness

1.0

0

0

0

Skin disorders

 

 

 

 

Rash

0.8

1.0

1.2

0.7

MedDRA version 7.1

Adverse reactions considered by investigators to be causally related to Bonviva are listed below by System Organ Class.

Frequencies are defined as common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), and rare (≥ 1/10,000 to < 1/1,000). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

 

Table 1: Adverse reactions occurring in postmenopausal women receiving Bonviva 150mg once monthly or ibandronic acid 2.5mg daily in the phase III studies BM16549 and MF4411.

 

System Organ Class

Frequency

Adverse reactions

Immune system disorders

Rare

Hypersensitivity reaction

Nervous system disorders

Common

Headache

 

Uncommon

Dizziness

Gastrointestinal disorders

Common

Oesophagitis, Gastritis, Gastro oesophageal reflux disease, Dyspepsia, Diarrhoea, Abdominal pain, Nausea

 

Uncommon

Oesophagitis including oesophageal ulcerations or strictures and dysphagia, Vomiting, Flatulence

 

Rare

Duodenitis

Skin and subcutaneous tissues disorders

Common

Rash

 

Rare

Angioedema, Face oedema, Urticaria

Musculoskeletal, connective tissue and bone disorders

Common

Arthralgia, Myalgia, Musculoskeletal pain, Muscle cramp, Musculoskeletal stiffness

 

Uncommon

Back pain

General disorders and administration site conditions

Common

Influenza like illness*

 

Uncommon

Fatigue

MedDRA version 7.1

* Transient, influenza-like symptoms have been reported with Bonviva 150 mg once monthly, typically in association with the first dose. Such symptoms were generally of short duration, mild or moderate in intensity, and resolved during continuing treatment without requiring remedial measures. 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.

Adverse reactions occurring at a frequency of less than or equal to 1 %

 

The following list provides information on adverse reactions reported in study MF 4411 occurring more frequently with ibandronic acid 2.5 mg daily than with placebo and study BM 16549 occurring more frequently with Bonviva 150 mg once monthly than with ibandronic acid 2.5 mg daily. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness:

 

Uncommon (1/100 – 1/1,000)

Gastro-intestinal Disorders:                                                       gastritis, oesophagitis including oesophageal

                                                                                                            ulcerations or strictures, vomiting,

                                                                                                            dysphagia

Nervous System Disorders:                                                       dizziness

Musculoskeletal and Connective Tissue Disorders:         back pain

 

Rare (1/1,000 – 1/10,000)

Gastro-intestinal Disorders:                                                       duodenitis

Immune System Disorders:                                                        hypersensitivity reactions

Skin and Subcutaneous Tissue Disorders:                       angioedema, face oedema, urticaria

 

 

 

Reasons for adding or updating:

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for Use

Date of revision of text on the SPC:23-02-2009

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



Underlined text has been added, text with strike through deleted:

 

2.       QUALITATIVE AND QUANTITATIVE COMPOSITION

 

One pre-filled syringe of 3 ml solution contains 3 mg ibandronic acid (as 3.375 mg ibandronic acid, monosodium salt, monohydrate).

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

For a full list of excipients, see section 6.1.

 

4.2     Posology and method of administration

Paediatric Ppopulation

Children and adolescents

There is no relevant use of Bonviva experience in children, and Bonviva was not studied in the paediatric population .

 

Method of Administration:

For intravenous use.

 

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

 

4.4     Special warnings and precautions for use

 

Administration failures

Strict adherence to the intravenous route of administration is required. Care must be taken not to administer Bonviva injection via intra-arterial or paravenous administration as this could lead to tissue damage.

 

 

 

Hypocalcaemia and Mineral Metabolism

Bonviva, like other bisphosphonates administered intravenously, may cause a transient decrease in serum calcium values.

 

Existing Hhypocalcaemia 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.

 

Route of administration

Strict adherence to the intravenous route of administration is required. Care must be taken not to administer Bonviva injection via intra-arterial or paravenous administration as this could lead to tissue damage.

 

Reasons for adding or updating:

  • Change to section 9 - Date of first Authorisation/renewal of the Authorisation
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:01-10-2006

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

9.    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
 
Amended: 23.02.2004
 
10.    DATE OF REVISION OF THE TEXT
 
Updated to: October 2006

Reasons for adding or updating:

  • Correction of spelling/typing errors

Reasons for adding or updating:

  • Correction of spelling/typing errors

Reasons for adding or updating:

  • Change to section 1 - trade name
  • Change to section 4.1 - Therapeutic Indications
  • Change to section 4.2 - Posology and Method of Administration
  • Change to section 4.4 - Special Warnings and Precautions for Use
  • Change to section 4.8 - Undesirable Effects
  • Change to section 5.1 - Pharmacodynamic Properties
  • Change to section 10 (date of (partial) revision of the text

Date of revision of text on the SPC:01-08-2006

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Due to detailed changes to this SPC, please copy and paste the following url into your web browser to view the change details:
 

Reasons for adding or updating:

  • Improved Electronic Presentation

Reasons for adding or updating:

  • New SPC for new product