Updated on 27/03/2012 and displayed until Current
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Reasons for adding or updating:
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Change to section 4.4 - Special warnings and precautions for Use
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| Date of revision of text on the SPC: 21-Mar-2012 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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Section 4.4 (Special warnings and precautions for use): The following paragraph has been added towards to the end of this section
'Depression, including suicidal ideation and behaviors, has been reported, particularly in patients with a pre-existing history of depression or psychiatric illness. Caution should be used in patients with a pre-existing history of depression or psychiatric illness'.
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Updated on 28/02/2012 and displayed until 27/03/2012
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Reasons for adding or updating:
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Change to section 4.8 - Undesirable Effects
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Change to section 5.1 - Pharmacodynamic Properties
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| Date of revision of text on the SPC: 17-Feb-2012 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
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The SmPC has been updated with the 156 weeks efficacy/safety data from the ongoing Phase III study (Protocol 021) in treatment naïve patients (3 year STARTMRK data). As a consequence sections 4.8 "Undesirable Effects" and 5.1 "Pharmacodynamic Properties" of the SmPC have also been updated.
Section 4.8: The following changes have been made to this section:
New sub heading have been included.
Information regarding the number of patients in the STARTMRK study has been updated.
The adverse event term of "Lymph node abscess" has been added under the list of 'uncommon' side effects for 'infections and infestations'.
The adverse event term of "decreased appetite" has been added under the list of 'common' side effects for 'Metabolism and nutrition disorders'.
The adverse event terms of "anorexia and decreased appetite" has been removed under the list of 'uncommon' side effects for 'Metabolism and nutrition disorders'.
The adverse event term of "nightmare" has been added under the list of 'common' side effects for 'Psychiatric disorders' and removed from the list of 'uncommon' side effects.
The adverse event terms of "hepatitis alcoholic" has been added under the list of 'uncommon' side effects for 'Hepato-biliary disorders'.
The adverse event terms of "lipoatrophy" has been added under the list of 'uncommon' side effects for 'Skin and subcutaneous tissue disorders'.
The adverse event terms of "submandibular mass" has been added under the list of 'uncommon' side effects for 'General disorders and administration site conditions'.
The adverse event terms of "blood pancreatic amylase increased" has been added under the list of 'common' side effects for 'Investigations' and the adverse event of 'international ratio increased' has been added and "low density lipoprotein decreased" has been removed under the list of 'uncommon' side effects for 'Investigations'.
The following new information has been added as new section d:
d. Paediatric population: The safety and efficacy of ISENTRESS have not been established in paediatric patients.
Section 5.1: This section has been updated with the 156 weeks efficacy/safety data from the ongoing Phase III study (Protocol 021) in treatment naïve patients.
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Updated on 02/12/2011 and displayed until 28/02/2012
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Reasons for adding or updating:
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Change to section 4.4 - Special warnings and precautions for Use
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Change to section 4.8 - Undesirable Effects
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| Date of revision of text on the SPC: 21-Nov-2011 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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Section 4.4: The following text has been added
"Severe skin and hypersensitivity reactions Severe, potentially life-threatening, and fatal skin reactions have been reported in patients taking ISENTRESS, in most cases concomitantly with other drugs associated with these reactions. These include cases of Stevens-Johnson syndrome and toxic epidermal necrolysis. Hypersensitivity reactions have also been reported and were characterized by rash, constitutional findings, and sometimes, organ dysfunction, including hepatic failure. Discontinue ISENTRESS and other suspect agents immediately if signs or symptoms of severe skin reactions or hypersensitivity reactions develop (including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema). Clinical status including liver aminotransferases should be monitored and appropriate therapy initiated. Delay in stopping ISENTRESS treatment or other suspect agents after the onset of severe rash may result in a life-threatening reaction"
Section 4.8: The adverse event term of
"drug rash with eosinophilia and systemic symptoms (DRESS)" has been added as an adverse event under Skin and subcutaneous tissue disorders.
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Updated on 23/09/2010 and displayed until 02/12/2011
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Reasons for adding or updating:
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Change to section 4.4 - Special warnings and precautions for Use
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Change to section 4.8 - Undesirable Effects
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| Date of revision of text on the SPC: 02-Sep-2010 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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Section 4.4 Special warnings and precautions for use
The third paragraph from the end of this section begins "Myopathy and rhabdomyolysis have been reported.. .". The statement " however, the relationship of Isentress to these events is unknown." has been deleted.
Section 4.8 Undesirable effects
In this section, a table of adverse events has been provided. In the table "thrombocytopenia has been added under "blood and lymphatic system disorders" with a frequency of "uncommon". Also in the table "rhabdomyolysis" has been added under "Musculoskeletal and connective tissue disorders" and given a frequency of "uncommon".
Due to the updated SmPC guideline’s advice for estimating frequencies of adverse events, the frequency rating for "suicidal ideation, suicidal behaviour and Stevens Johnson syndrome" has been changed to " uncommon" from unknown.
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Updated on 15/04/2010 and displayed until 23/09/2010
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Reasons for adding or updating:
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Change to section 4.1 - Therapeutic indications
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Change to section 4.4 - Special warnings and precautions for Use
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Change to section 4.8 - Undesirable Effects
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Change to section 5.1 - Pharmacodynamic Properties
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| Date of revision of text on the SPC: 26-Mar-2010 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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Section 4.1 Therapeutic Indication - The indication is no longer based on 48 weeks duration of study as data from extended duration of treatment to 96 weeks is now available
Section 4.
4 Special warnings and Precautions for use - Addition of raltegravir/darunavir interaction and a warning for the occurrence of rashes as a result.
Section 4.8 Undesirable effects -
Addition of a the following information:
Change in the statistical numbers (i.e. in patient years, percentages) of the section following new data from the 96 weeks study.
Addition of the following side effects: upper respiratory infection, anaemia, lymphadenopathy, cachexia, hyperlipidaemia, suicide attempt, major depression, panic attack, erosive duodenitis, gingivitis, glossitis, aptic steatosis, facial wasting, flank pain, osteopenia, renal impairment, tubulointestinal nephritis, blood albumin decreased, low density lipoprotein decreased.
Frequency re-classification for 'lipase increased' and 'pyrexia' from uncommon to common.
Replacement of 'visual disturbance' with 'visual impairment' and 'stomach discomfort' with 'epigastric discomfort'.
Removal of 'lumbarisation'.
Section 5.1 Pharmacodynamic properties - The section has been updated with the data from the 96 weeks study.
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Updated on 17/09/2009 and displayed until 15/04/2010
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Reasons for adding or updating:
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Change to section 4.1 - Therapeutic indications
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Change to section 4.2 - Posology and method of administration
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Change to section 4.4 - Special warnings and precautions for Use
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Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
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Change to section 4.8 - Undesirable Effects
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Change to section 5.1 - Pharmacodynamic Properties
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| Date of revision of text on the SPC: 09-Sep-2009 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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Information from a 48-week study in treatment naive patients has been added to the SPC changing the following sections:
Section 4.1: The indication is no longer limited to treatment experienced patients and the product is now for use in both treatment experienced and treatment naive patients.
Section 4.2: Reference to the 48-week treatment naïve data is added.
Section 4.4: Reference is added to administration of raltegravir with two other active ARTs.
Reference is added to administration of raltegravir with two other active ARTs.
Test specific to treatment experience study data has been removed.
Section 4.5: Addition of drugs interacting with raltegravir, such as methadone and etravirine, and respective changes to the table included therein.
Addition of drugs interacting with raltegravir, such as methadone and etravirine, and respective changes to the table included therein.
Section 4.8: A significant number of side effects have been added and the text has been updated to reflect the new 48-week treatment naïve data.
A significant number of side effects have been added and the text has been updated to reflect the new 48-week treatment naïve data.
Section 5.1: Respective sections have been added to reflect the new data and existing text has been changed to in relation to the new treatment naïve results from the 48-week study.
Respective sections have been added to reflect the new data and existing text has been changed to in relation to the new treatment naïve results from the 48-week study.
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Updated on 28/07/2009 and displayed until 17/09/2009
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Reasons for adding or updating:
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Change to section 5.1 - Pharmacodynamic Properties
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| Date of revision of text on the SPC: 14-Jul-2009 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
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| This product is no longer conditionally approved as it was when first licenced. It now has a full marketing authorisation. The paragraph detailing the conditional approval at the end of section 5.1 has now been deleted.
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Updated on 10/06/2009 and displayed until 28/07/2009
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Reasons for adding or updating:
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Change to section 5.3 - Preclinical Safety Data
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| Date of revision of text on the SPC: 28-May-2009 |
| Legal Category: POM |
| Black Triangle (CHM):
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The Following paragraph is added to section 5.3
Carcinogenicity
A carcinogenicity study of raltegravir in mice did not show any carcinogenic potential. At the highest dose levels, 400 mg/kg/day in females and 250 mg/kg/day in males, systemic exposure was similar to that at the clinical dose of 400 mg b.i.d. In rats, tumours (squamous cell carcinoma) of the nose/nasopharynx were identified at 300 and 600 mg/kg/day in females and at 300 mg/kg/day in
13 males. These neoplasia could result from local deposition and/or aspiration of drug on the mucosa of the nose/nasopharynx during oral gavage dosing and subsequent chronic irritation and inflammation; it is likely that they are of limited relevance for the intended clinical use. At the NOAEL, systemic exposure was similar to that at the clinical dose of 400 mg b.i.d. Standard genotoxicity studies to evaluate mutagenicity and clastogenicity were negative.
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Updated on 07/05/2009 and displayed until 10/06/2009
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Reasons for adding or updating:
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Change to section 4.8 - Undesirable Effects
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| Date of revision of text on the SPC: 21-Apr-2009 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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Section 4.8
Addition of suicidal ideation and suicidal behaviour in the table of listed side effects.
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Updated on 09/02/2009 and displayed until 07/05/2009
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Reasons for adding or updating:
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Correction of spelling/typing errors
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| Date of revision of text on the SPC: 23-Jan-2009 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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| None provided |
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Updated on 20/01/2009 and displayed until 09/02/2009
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Reasons for adding or updating:
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Change to section 4.1 - Therapeutic indications
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Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
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Change to section 4.8 - Undesirable Effects
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Change to section 5.1 - Pharmacodynamic Properties
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| Date of revision of text on the SPC: 07-Jan-2009 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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Section 4.1
The Isentress indication is updated such that it is now based upon 48 week data instead of 24 week data.
Section 4.5
New data on interaction of raltegravir with hormonal contraceptives has been added. The raltegravir AUC values under interaction with omeprazole have been updated.
Section 4.8
This section has been updated considerably. The statistics in the first two paragraphs have been updated. The side effects have been grouped in one table and a considerable number of new side effects have been added. These are listed by system organ class. The laboratory abnormalities values have been removed and the related information have been included under investigations in the grouped table.
Section 5.1
The section and table referring to the previously 24 week data have now been updated with the 48 week data.
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Updated on 12/09/2008 and displayed until 20/01/2009
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Reasons for adding or updating:
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Change to section 4.8 - Undesirable Effects
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| Date of revision of text on the SPC: 28-Aug-2008 |
| Legal Category: POM |
| Black Triangle (CHM):
YES |
Free-text change information supplied by the pharmaceutical company
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Update to section 4.8 side effects to include rash and Stevens Johnson Syndrome (SJS) as adverse events with an unknown frequency.
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Updated on 04/01/2008 and displayed until 12/09/2008
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