Last Updated on eMC 06-05-2016 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:25-04-2016

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Underline text = new text

Strike through text = deleted text

 

 

4.2     Posology and method of administration

 

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

 

Bondronat therapy should only be initiated by physicians experienced in the treatment of cancer.

 

[ … ]

 

4.4     Special warnings and precautions for use

 

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Osteonecrosis of the jaw

Osteonecrosis of the jaw (ONJ) has been reported very rarely in the post marketing setting in patients receiving Bondronat for oncology indications (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 Bondronat 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 Bondronat. While on treatment, invasive dental procedures should be performed only after careful consideration and be avoided in close proximity to Bondronat 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 Bondronat 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.

 

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4.8     Undesirable effects

 

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Table 1 Adverse Reactions Reported for Intravenous Administration of Bondronat

 

System Organ Class

Common

Uncommon

Rare

Very rare

Not known

 

[ … ]

 

 

 

 

 

 

Musculoskeletal and connective tissue disorders

Osteoarthritis, myalgia, arthralgia, joint disorder,

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.

 

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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.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

 

25 April 2016

 

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • 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:



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

 

4.2       Posology and method of administration

[…]

Patients with renal impairment

For patients with mild renal impairment (CLcr 50 and <80 mL/min) no dose adjustment is necessary. For patients with moderate renal impairment (CLcr ≥30 and <50 mL/min) or severe renal impairment (CLcr <30 mL/min) being treated for the prevention of skeletal events in patients with breast cancer and metastatic bone disease the following dosing recommendations should be followed (see section 5.2):

 

Creatinine Clearance (ml/min)

Dosage / Infusion time 1

Infusion Volume 2

50 CLcr <80

6 mg / 15 minutes

100 ml

30 CLcr <50

4 mg / 1 hour

500 ml

<30

2 mg / 1 hour

500 ml

1  Administration every 3 to 4 week

2  0.9% sodium chloride solution or 5% glucose solution

 

Creatinine Clearance (ml/min)

Dosage

Infusion Volume 1 and Time 2

50 CLcr<80

6 mg      (6 ml of concentrate for solution for infusion)

100 ml over 15 minutes

30 CLcr <50

4 mg      (4 ml of concentrate for solution for infusion)

500 ml over 1 hour

<30

2 mg      (2 ml of concentrate for solution for infusion)

500 ml over 1 hour

1  0.9% sodium chloride solution or 5% glucose solution

2  Administration every 3 to 4 week

[…]

4.8       Undesirable effects

[…]

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

[…]

10.          DATE OF REVISION OF THE TEXT

 

28 May 2015

 

Reasons for adding or updating:

  • New individual SPC (was previously included in joint SPC)

Date of revision of text on the SPC:01-01-0001

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Underlined Text = new text
Struck Through Text = deleted text

4.2     Posology and method of administration

 

[ … ]

 

Special populations

 

Patients with hepatic impairment

No dose adjustment is required (see section 5.2).

 

[ … ]

 

Paediatric population

The safety and efficacy of Bondronat in children and adolescents below the age of 18 years have not been established. No data are available (see section 5.1 and section 5.2).

 

[ … ]

 

For single use only. Only clear solution without particles should be used.

Bondronat concentrate for solution for infusion should be administered as an intravenous infusion.

As the inadvertent intra-arterial administration of preparations not expressly recommended for this purpose as well as paravenous administration can lead to tissue damage, cCare must be taken not to administer ensure that Bondronat concentrate for solution for infusion via intra-arterial or paravenous administration, as this could lead to tissue damage. is administered intravenously.

 

4.4     Special warnings and precautions for use

 

[ … ]

 

Osteonecrosis of the jaw (ONJ)

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.

 

[ … ]

 

Excipients with known effect

Bondronat is essentially sodium free.

 

4.6     Fertility, pregnancy and lactation

 

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Fertility

There are no data on the effects of ibandronic acid from in humans. In reproductive studies in rats by the oral route, ibandronic acid decreased fertility. In studies in rats using the intravenous route, ibandronic acid decreased fertility at high daily doses (see section 5.3).

 

4.8     Undesirable effects

 

Summary of  the Ssafety Pprofile

The safety profile for Bondronat is derived from controlled clinical trials in the respective indications after the intravenous administration of Bondronat at the recommended doses, and from 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).

 

In the tTreatment of tumour induced hypercalcaemia treatment was is most frequently associated with a rise in body temperature. Less frequently, a decrease in serum calcium below normal range (hypocalcaemia) was is reported. In most cases no specific treatment was required and the symptoms subsided after a couple of hours/days.

In the prevention of skeletal events in patients with breast cancer and bone metastases, treatment was is most frequently associated with asthenia followed by rise in body temperature and headache.

 

[ … ]

 

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

 

Table 1 Adverse Reactions Reported for Intravenous Administration of Bondronat

 

Adverse reactions are listed according to MedRA 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

Not known

 

[ … ]

 

 

 

 

 

 

Immune system disorders

 

 

 

Hypersensitivity†,

 bronchospasm†,

angioedema†,

anaphylactic reaction/shock†**

Asthma exacerbation

 

[ … ]

 

 

 

 

 

 

Nervous system disorders

Headache, dizziness, dysgeusia (taste perversion)

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

 

 

 

 

[ … ]

 

 

 

 

 

 

**See further information below

†Identified in post-marketing experience.

 

[ … ]

 

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(see details below).

 

 

Ireland

IMB Pharmacovigilance

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

 

5.1     Pharmacodynamic properties

 

[ … ]

 

Prevention of skeletal events in patients with breast cancer and bone metastases with Bondronat 6 mg administered intravenously was assessed in one randomized placebo controlled phase III trial with a duration of 96 weeks. Female patients with breast cancer and radiologically confirmed bone metastases were randomised to receive placebo (158 patients) or 6 mg Bondronat (154 patients). The results from this trial are summarised below.

 

[ … ]

 

Paediatric population (see section 4.2 and section 5.2)

The safety and efficacy of Bondronat in children and adolescents below the age of 18 years have not been established. No data are available.

 

10.       DATE OF REVISION OF THE TEXT

 

20 March 2014

 

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