Janssen-Cilag Ltd

Change to section 2

Updated in-line with new QRD template

Change to section 4.2

Updated in-line with new QRD template

Change to section 4.4

Deletion of amyloidosis text.

Change to section 4.6

Updated in-line with new QRD template

Change to section 5.1

Addition of information on patients with previously treated light-chain (AL) amyloidosis

Change to section 6.5

Updated in-line with new QRD template

Change to section 10

Changed to 2^nd July 2010

4.4 - Special Warnings and Precautions for Use

Addition of: Reversible Posterior Leukoencephalopathy Syndrome (RPLS).

4.8 - Undesirable effects

Addition of:

Reversible Posterior Leukoencephalopathy Syndrome (RPLS)

Acute febrile neutrophilic dermatosis (Sweet’s syndrome)

Vasculitic rash (including leukocytoclastic vasculitis)

10 - DATE OF REVISION OF THE TEXT

Changed to 27/04/2010

Change to section 4.5 –Interaction with other medicinal products and other forms of interaction

Deletion of: Patients should be closely monitored when given bortezomib in combination with CYP2C19-inhibitors (e.g. fluoxetine).

Change to section 10 – Date of revision of the text

Changed to 30^th November 2009

Change to section 5.1 - Pharmacodynamic properties

Data from in vitro, ex-vivo, and animal models with bortezomib suggest that it increases osteoblast differentiation and activity and inhibits osteoclast function. These effects have been observed in patients with multiple myeloma affected by an advanced osteolytic disease and treated with bortezomib.

Change to section 10 – Date of revision of the text

Changed to 28^th October 2009

Change to section 4.2 – Posology and |Method of Administration

Renewal Approved

Change to section 4.3 – Contra-indications

Renewal Approved

Change to section 4.4 – Special Warnings and Precautions for Use

Renewal Approved

Change to section 4.5 –Interaction with other medicinal products and other forms of interaction

Renewal Approved

Change to section 4.6 – Pregnancy and Lactation

Renewal Approved

Change to section 4.7 - Effects on Ability to Drive and Use Machines

Renewal Approved

Change to section 4.8 – Undesirable effects

recommendation to consider the use of antiviral prophylaxis therapy in patients treated with Velcade and to include Steven Johnson Syndrome and Toxic Epidermal Necrolysis as very rare ADR’s in the postmarketing section

Change to section 4.9 - Overdose

Renewal Approved

Change to section 5.1 - Pharmacodynamic properties

Renewal Approved

Change to section 5.2 - Pharmacokinetic properties

Renewal Approved

Change to section 5.3 - Preclinical Safety Data

Renewal Approved

Change to section 6.3 – Shelf Life

Renewal Approved

Change to section 6.4 – Special Precautions for Storage

Renewal Approved

Change to section 6.5 – Nature and Contents of Container*

Renewal Approved

Change to section 6.6 –  Instructions for use, handling and disposal*

Renewal Approved

Change to section 9 – Date of Renewal of Authorisation

Changed to 26/04/2009

Change to section 10 – Date of revision of the text

Changed to 29^th May 2009

Change to section 4.1 – Therapeutic Indications

Velcade can now be used in combination with melphalan and prednisone for the treatment of patients with previously untreated multiple myeloma who are not eligible for high-dose chemotherapy with bone marrow transplant.

Change to section 4.2 – Posology and |Method of Administration

Details of usage in Monotherapy and Combination therapy

Change to section 4.5 –Interaction with other medicinal products and other forms of interaction

Information on a drug-drug interaction study assessing the effect of melphalan-prednisone on VELCADE.

Change to section 4.8 – Undesirable effects

Summary of safety data in patients with previously untreated multiple myeloma

Change to section 5.1 - Pharmacodynamic properties

Information on a Randomized, Open-Label Clinical Study in Patients with Previously Untreated Multiple Myeloma

Change to section 10 – Date of revision of the text

29^th August 2008

X

Change to section 4.2 – Posology and |Method of Administration

Addition of information regarding use in patients with impaired renal function

X

Change to section 4.4 – Special Warnings and Precautions for Use

Addition of information regarding use in patients with impaired renal function

X

Change to section 5.2 - Pharmacokinetic properties

Addition of information regarding use in patients with impaired renal function

4.3

Contraindications

Addition of - Acute diffuse infiltrative pulmonary and pericardial disease.

4.4

Special Warnings and Precautions for Use

Pulmonary Disorders addition of - A pretreatment chest radiograph is recommended to determine if any additional diagnostic measures are necessary and to serve as a baseline for potential post-treatment pulmonary changes.

In the event of new or worsening pulmonary symptoms - The benefit/risk ratio should be considered prior to continuing VELCADE therapy.

4.8

Undesirable effects

Cardiac disorders addition of - pericarditis, cardiac and cardiopulmonary arrest, ventricular arrhythmias, atrio-ventricular block complete, atrial fibrillation, tachycardia, sinus and ventricular tachycardia

Respiratory, thoracic and mediastinal disorders addition of – pneumonia, acute diffuse infiltrative pulmonary disease, pulmonary hypertension, respiratory failure, pulmonary alveolar haemorrhage, acute pulmonary oedema, pulmonary oedema, pulmonary embolism, peripheral embolism

6.5

Nature and contents of container

Addition of - The cap colour of the 10 ml vial is royal blue.

10.

DATE OF REVISION OF THE TEXT

Updated to 21^st April 2008

Change to section 4.2 – Posology and Method of Administration

Change to content of Table 1

Change to section 4.4 – Special Warnings and Precautions for Use

Update to text on Peripheral Neuropathy, Hypotension and Pulmonary Disorders

Change to section 4.8 – Undesirable effects

Update to entire section

Change to section 5.2 - Pharmacokinetic properties

Update to entire section

Change to section 10 – Date of revision of the text

Changed to 30/07/2007

4.8 Undesirable effects - Position of sections headed Endocrine disorders and Reproductive system and breast disorders moved.

5.1 Pharmacodynamic properties - Additional statement:

This medicinal product has been authorised under “Exceptional Circumstances.” This means that for scientific reasons it has not been possible to obtain complete information on this medicinal product. The European Medicines Agency (EMEA) will review any new information which may become available each year and this SPC will be updated as necessary.

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION –

Add:

Renewal of the authorisation: 03/01/2007

10. DATE OF REVISION OF THE TEXT - 03/01/2007

4.4

Special Warnings and Precautions for Use

Addition of text:

Pulmonary Disorders

There have been rare reports of acute diffuse infiltrative pulmonary disease of unknown aetiology such as pneumonitis, interstitial pneumonia, lung infiltration, and Acute Respiratory Distress Syndrome (ARDS) in patients receiving VELCADE (see section 4.8). Some of these events have been fatal.  A higher proportion of these events have been reported in Japan.  In the event of new or worsening pulmonary symptoms (e.g. cough, dyspnoea), a prompt diagnostic evaluation should be performed and patients treated appropriately.

4.8

Undesirable effects

Change to text:

Post Marketing Experience

Clinically significant adverse reactions are listed if they have been reported during post approval use of VELCADE and have not been reported in clinical trials. Their frequency is not known.

Nervous system disorders

Encephalopathy

Cardiac disorders

Cardiac tamponade

Respiratory, thoracic and mediastinal disorders (see section 4.4)

Pneumonitis, interstitial pneumonia, Acute Respiratory Distress Syndrome (ARDS)

Gastrointestinal disorders

Ischemic colitis

Hepatobiliary disorders

Liver failure

10.

DATE OF REVISION OF THE TEXT

Changed to 28/07/2006