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Actos Tablets

Last Updated on eMC 27-Jun-2014 View document  | Takeda UK Ltd 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.

Updated on 27-Jun-2014 and displayed until Current

Reasons for adding or updating:

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • 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 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 7 - Marketing authorisation holder
  • Change to section 9 - Date of first authorisation/renewal of the authorisation
  • Change to section 10 - Date of revision of the text
  • Correction of spelling/typing errors
  • Improved presentation of SPC

Date of revision of text on the SPC: 16-Jun-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



 

Section  2. QUALITATIVE AND QUANTITATIVE COMPOSITION

 

-          Addition of the highlighted text:

 Excipients with known effect:

 

-          Replacement of the word ‘a’ with ‘the’:

For a the full list of excipients, see section 6.1

 

Section 4.1 Therapeutic indications

 

-     Formatting change to subscript of the highlighted text in the final paragraph of the section:

     HbA1c  

 

Section 4.2 Posology and method of administration

 

             -Formatting of subheading  Paediatric population to convert to italics, and removal of underline.

 

 

Section 4.3 Contraindications

 

-          Addition of the highlighted text:

hypersensitivity to the active substance or to any of the excipients listed in 6.1

 

 

Section 4.4 Special warnings and precautions for use

 

-     Formatting of the following subheadings to add underline:

 

Fluid retention and cardiac failure

Elderly

Bladder Cancer

Monitoring of liver function

Weight gain

Haematology
Hypoglycaemia
Eye disorders

Others


        Section 4.6 Fertility, pregnancy and lactation

 

-     Formatting of highlighted subheading :

             Pregnancy  changed to non-italics, and underline added.

-     Formatting of highlighted subheading :

-     Breast-feeding changed to non-italics, hyphen and underline added.

-     Formatting of highlighted text, addition of hyphen:

             breast‑feeding

-     Formatting of highlighted subheading :

-     Fertility changed to non-italics, and underline added.

 

Section 4.7 Effects on ability to drive and use machines

 

-          Replacement of the word  ‘effect’ with ‘influence’:

Actos has no or negligible effect  influence on the ability to drive and use machines.

 

Section 4.8 Undesirable effects

 

-          Addition of the following subheading text underlined:

Tabulated list of adverse reactions


-
         
Amendment to wording in the following paragraph with insertion of highlighted text and deletion of crossed out text:

 

Adverse reactions reported in excess (> 0.5%) of placebo and as more than an isolated case in patients receiving pioglitazone in double-blind studies are listed below as MedDRA preferred term by system organ class and absolute frequency. Frequencies are defined as: 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 system organ class, adverse reactions are presented in order of decreasing incidence and  followed by decreasing seriousness.

 

-          Formatting of table

 

-          Addition of the following subheading text underlined:

Description of selected adverse reactions


-    
   Insertion of the following paragraph:

 

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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

 

-          In the following paragraph, amendment of ‘significant’ to ‘significantly’ (highlighted):

 

In clinical trials of up to two years duration, pioglitazone reduced total plasma triglycerides and free fatty acids, and increased HDL cholesterol levels, compared with placebo, metformin or gliclazide. Pioglitazone did not cause statistically significant increases in LDL cholesterol levels compared with placebo, whilst reductions were observed with metformin and gliclazide. In a 20-week study, as well as reducing fasting triglycerides, pioglitazone reduced post prandial hypertriglyceridaemia through an effect on both absorbed and hepatically synthesised triglycerides. These effects were independent of pioglitazone’s effects on glycaemia and were statistically significantly different to glibenclamide.

 

-     Formatting of subheading  Paediatric population to remove italics, and addition of underline

 

 

Section 5.2 Pharmacokinetic properties

 

      - Formatting of the following subheadings to add underline and remove italics:

 

Absorption

Distribution

Biotransformation

Elimination

Elderly

Patients with renal impairment

Patients with hepatic impairment

 

-     Under the subheading Distribution, text has been amended from ‘l’ to ‘L’ in the following sentence:  The estimated volume of distribution in humans is 0.25 L/kg.

 

 

Section 5.3 Preclinical safety data

 

-     Formatting of the following with amendments highlighted and addition of underline:

 

    Environmental Risk Assessment (ERA):

     Nno environmental impact is anticipated from the clinical use of pioglitazone.

 

 

Section 7. MARKETING AUTHORISATION HOLDER

 

-      MA holder address amended to:

 

Takeda Pharma A/S

Dybendal Alle 10,

DK-2630 Taastrup

Denmark

 

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

 

-     Amendment of wording with insertion of ‘latest’ as follows:

    Date of last latest renewal:

 

Section 10. DATE OF REVISION OF THE TEXT

 

Updated to 16/06/2014

Updated on 29-Nov-2013 and displayed until 27-Jun-2014

Reasons for adding or updating:

  • 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: 13-Nov-2013

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 4.4 addition of the following text:
Post marketing cases of peripheral oedema and cardiac failure have also been reported in patients with concomitant use of pioglitazone and nonsteroidal anti-inflammatory drugs, including selective COX-2 inhibitors

Some epidemiological studies have suggested a similarly increased risk of fracture in both men and women.

Section 4.4 amendment of wording as follows:

The risk of fractures should be considered in the long term care of patients (previously women) treated with pioglitazone.

Section 4.8 Addition of the following text:
However, this did not lead to an increase in mortality in this study. In this study in patients receiving pioglitazone and insulin, a higher percentage of patients with heart failure was observed in patients  aged ≥65 years compared with those less than 65 years (9.7% compared to 4.0%). In patients on insulin with no pioglitazone the incidence of heart failure was 8.2% in those ≥65 years compared to 4.0% in patients less than 65 years.

Section 4.8 Removal of the word "rarely" and replacement of  the word "but" with "and" 
Heart failure has been reported (rarely) with marketing use of pioglitazone and more frequently when pioglitazone was used in combination with insulin or in patients with a history of cardiac failure.

Updated on 16-May-2013 and displayed until 29-Nov-2013

Reasons for adding or updating:

  • Change to section 7 - Marketing authorisation holder

Date of revision of text on the SPC: 29-Apr-2013

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



The Actos SmPCs contains updated information in the following section:

 

7. Marketing Authourisation Holders has been updated from;

 

Takeda Global Research and Development Centre (Europe) Ltd

61 Aldwych

London WC2B 4AE

United Kingdom

 

To

 

Takeda Pharma A/S

Langebjerg 1

DK-4000 Roskilde

Denmark

Updated on 10-Jan-2013 and displayed until 16-May-2013

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: 18-Dec-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 4.8 Undesirable effects

Under new adverse reaction class of immune system disorders ‘Hypersensitivity and allergic reactions’ have been added with a frequency of ‘Not known’.

 

In addition a footnote states ‘Postmarketing reports of hypersensitivity reactions in patients treated with pioglitazone have been reported. These reactions include anaphylaxis, angioedema, and urticaria’

Updated on 19-Jan-2012 and displayed until 10-Jan-2013

Reasons for adding or updating:

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • 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 10 date of revision of the text

Date of revision of text on the SPC: 22-Dec-2011

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



4.1 Therapeutic indications -Pioglitazone is indicated

 

as second or third line treatment of type 2 diabetes mellitus as described below. Added

 

After initiation of therapy with pioglitazone, patients should be reviewed after 3 to 6 months to assess adequacy of response to treatment (e.g. reduction in HbA1c). In patients who fail to show an adequate response, pioglitazone should be discontinued. In light of potential risks with prolonged therapy, prescribers should confirm at subsequent routine reviews that the benefit of pioglitazone is maintained (see section 4.4). Added

 

4.2.Posology and method of administration - Elderly:

 

Physicians should start treatment with the lowest available dose and increase the dose gradually, particularly when pioglitazone is used in combination with insulin (see section 4.4 Fluid retention and cardiac failure).

4.3 Contraindications
- Current bladder cancer or a history of bladder cancer and Uninvestigated macroscopic haematuria. Added

4.4 Special warnings and precautions for use-Elderly Combination use with insulin should be considered with caution in the elderly because of increased risk of serious heart failure. In light of agerelated risks (especially bladder cancer, fractures and heart failure), the balance of benefits and risks should be considered carefully both before and during treatment in the elderly.Added

 

Bladder Cancer -Cases of bladder cancer were reported more frequently in a meta

 

analysis of controlled clinical trials with pioglitazone (19 cases from 12506 patients, 0.15%) than in control groups (7 cases from 10212 patients, 0.07%) HR=2.64 (95% CI 1.116.31, P=0.029). After excluding patients in whom exposure to study drug was less than one year at the time of diagnosis of bladder cancer, there were 7 cases (0.06%) on pioglitazone and 2 cases (0.02%) in control groups. Available epidemiological data also suggest a small increased risk of bladder cancer in diabetic patients treated with pioglitazone in particular in patients treated for the longest durations and with the highest cumulative doses. A possible risk after short term treatment cannot be excluded.  Risk factors for bladder cancer should be assessed before initiating pioglitazone treatment (risks include age, smoking history, exposure to some occupational or chemotherapy agents e.g. cyclophosphamide or prior radiation treatment in the pelvic region). Any macroscopic haematuria should be investigated before starting pioglitazone therapy. Patients should be advised to promptly seek the attention of their physician if macroscopic haematuria or other symptoms such as dysuria or urinary urgency develop during treatment. Added

 

4.8 Undesirable effects Under

 

Neoplasms benign, malignant and unspecified (including cysts and polyps)bladder cancer has been added as an Uncommon effect. Added.

10. Date of revision of the text 22 December 2011.  updated

 

Updated on 06-Oct-2011 and displayed until 19-Jan-2012

Reasons for adding or updating:

  • Removal of Black Triangle

Date of revision of text on the SPC: 31-Aug-2010

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Removal of Black Triangle

Updated on 15-Nov-2010 and displayed until 06-Oct-2011

Reasons for adding or updating:

  • Change to section 4.6 - 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 5.2 - Pharmacokinetic Properties
  • Change to section 5.3 - Preclinical Safety Data
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration

Date of revision of text on the SPC: 31-Aug-2010

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



Updated SmPC wording (main changes to be aware of)

Summary of change

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Excipients:

Each 15 mg tablet contains 92.87 mg of lactose monohydrate (see section 4.4).

Each 30 mg tablet contains 76.34 mg of lactose monohydrate (see section 4.4).

Each 45 mg tablet contains 114.51 mg of lactose monohydrate (see section 4.4).

Lactose content has been added to this section

4.1       Therapeutic indications

as monotherapy

-               in adult patients (particularly overweight patients) inadequately controlled by diet and exercise for whom metformin is inappropriate because of contraindications or intolerance

 

as dual oral therapy in combination with

-                 metformin, in adult patients (particularly overweight patients) with insufficient glycaemic control despite maximal tolerated dose of monotherapy with metformin

-                 a sulphonylurea, only in adult patients who show intolerance to metformin or for whom metformin is contraindicated, with insufficient glycaemic control despite maximal tolerated dose of monotherapy with a sulphonylurea.

 

as triple oral therapy in combination with

-                 metformin and a sulphonylurea, in adult patients (particularly overweight patients) with insufficient glycaemic control despite dual oral therapy.

Change to wording to include indicated in ADULT patients.

 

4.2 Posology and method of administration

Special population

Elderly

No dose adjustment is necessary for elderly patients (see section 5.2).

 

Renal impairment

No dose adjustment is necessary in patients with impaired renal function (creatinine clearance > 4 ml/min) (see section 5.2). No information is available from dialysed patients therefore pioglitazone should not be used in such patients.

 

Hepatic impairment

Pioglitazone should not be used in patients with hepatic impairment (see section 4.3 and 4.4).

 

Paediatric population

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

 

Method of administration

Pioglitazone tablets are taken orally once daily with or without food. Tablets should be swallowed with a glass of water.

Restructured

4.6       Fertility, pregnancy and lactation

Fertility

In animal fertility studies there was no effect on copulation, impregnation or fertility index

Information on animal fertility has been added to this section

4.7       Effects on ability to drive and use machines

Actos has no or negligible effect on the ability to drive and use machines. However patients who experience visual disturbance should be cautious when driving or using machines.

Information for patients who experience  visual disturbances has been added

4.8     Undesirable effects

No new events have been reported, but the information is now presented in a table

5.2       Pharmacokinetic properties

Metabolism section has been re-worded to Biotransformation

 

Addition of Biotransformation

5.3       Preclinical safety data

Environmental Risk Assessment: no environmental impact is anticipated from the clinical use of pioglitazone.

Information in bold has been added to this section

Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu

Added at the end of the SmPC

Updated on 21-Apr-2010 and displayed until 15-Nov-2010

Reasons for adding or updating:

  • Change to section 5.3 - Preclinical Safety Data

Date of revision of text on the SPC: 31-Mar-2010

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



In section 5.3 Preclinical safety data, the following wording has been added,

 

“The formation and presence of urinary calculi with subsequent irritation and hyperplasia was postulated as the mechanistic basis for the observed tumourigenic response in the male rat. A 24-month mechanistic study in male rats demonstrated that administration of pioglitazone resulted in an increased incidence of hyperplastic changes in the bladder. Dietary acidification significantly decreased but did not abolish the incidence of tumours . The presence of microcrystals exacerbated the hyperplastic response but was not considered to be the primary cause of hyperplastic changes. The relevance to humans of the tumourigenic findings in the male rat cannot be excluded.”

 

Updated on 16-Apr-2009 and displayed until 21-Apr-2010

Reasons for adding or updating:

  • Change to section 3 - Pharmaceutical form
  • Change to MA holder contact details

Date of revision of text on the SPC: 24-Feb-2009

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

3. PHARMACEUTICAL FORM

Tablet.

The tablets are white to off-white, round, convex and marked ‘15’ on one face and ‘ACTOS’ on the other face.
The tablets are white to off-white, round, flat and marked ‘30’ on one face and ‘ACTOS’ on the other face.
The tablets are white to off-white, round, flat and marked ‘45’ on one face and ‘ACTOS’ on the other face.

7. MARKETING AUTHORISATION HOLDER

Takeda Global Research and Development Centre (Europe) Ltd
61 Aldwych
London
WC2B 4AE
United Kingdom

Updated on 06-Sep-2007 and displayed until 16-Apr-2009

Reasons for adding or updating:

  • 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: 01-Aug-2007

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

4.4     Special warnings and precautions for use
 

Others:

 An increased incidence in bone fractures in women was seen in a pooled analysis of adverse event reports of bone fracture from randomised, controlled, double blind clinical trials in over 8100 pioglitazone and 7400 comparator treated patients, on treatment for up to 3.5 years.

 Fractures were observed in 2.6% of women taking pioglitazone compared to 1.7% of women treated with a comparator. No increase in fracture rates was observed in men treated with pioglitazone (1.3%) versus comparator (1.5%).

 The fracture incidence calculated was 1.9 fractures per 100 patient years in women treated with pioglitazone and 1.1 fractures per 100 patient years in women treated with a comparator.  The observed excess risk of fractures for women in this dataset on pioglitazone is therefore 0.8 fractures per 100 patient years of use.

 In the 3.5 year cardiovascular risk PROactive study, 44/870 (5.1%; 1.0 fractures per 100 patient years) of pioglitazone-treated female patients experienced fractures compared to 23/905 (2.5%; 0.5 fractures per 100 patient years) of female patients treated with comparator. No increase in fracture rates was observed in men treated with pioglitazone (1.7%) versus comparator (2.1%).

 The risk of fractures should be considered in the long term care of women treated with pioglitazone.
 
  4.8     Undesirable effects 

A pooled analysis was conducted of adverse event reports of bone fractures from randomised, comparator controlled, double blind clinical trials in over 8100 patients in the pioglitazone-treated groups and 7400 in the comparator-treated groups of up to 3.5 years duration.  A higher rate of fractures was observed in women taking pioglitazone (2.6%) versus comparator (1.7%).  No increase in fracture rates was observed in men treated with pioglitazone (1.3%) versus comparator (1.5%).

Updated on 20-Feb-2007 and displayed until 06-Sep-2007

Reasons for adding or updating:

  • Addition of Black Triangle

Date of revision of text on the SPC: 01-Feb-2007

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Addition of the black triangle

Updated on 06-Feb-2007 and displayed until 20-Feb-2007

Reasons for adding or updating:

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • 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

Date of revision of text on the SPC: 01-Jan-2007

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

4.      CLINICAL PARTICULARS

4.1    Therapeutic indications

Pioglitazone is also indicated for combination with insulin in type 2 diabetes mellitus patients with insufficient glycaemic control on insulin for whom metformin is inappropriate because of contraindications or intolerance (see section 4.4). 

4.2    Posology and method of administration

In combination with insulin, the current insulin dose can be continued upon initiation of pioglitazone therapy.  If patients report hypoglycaemia, the dose of insulin should be decreased.

4.3    Contraindications

-                Diabetic ketoacidosis.

4.4   Special warnings and precautions for use

Fluid retention and cardiac failure:

Pioglitazone can cause fluid retention, which may exacerbate or precipitate heart failure. Patients should be observed for signs and symptoms of heart failure, weight gain or oedema particularly those with reduced cardiac reserve. There have been cases of cardiac failure reported from the market when pioglitazone was used in combination with insulin or in patients with a history of cardiac failure; patients should be observed for signs and symptoms of heart failure, weight gain and oedema when pioglitazone is used in combination with insulin. Since insulin and pioglitazone are associated with fluid retention, concomitant administration may increase the risk of oedema. Pioglitazone should be discontinued if any deterioration in cardiac status occurs.

A cardiovascular outcome study of pioglitazone has been performed in patients under 75 years with type 2 diabetes mellitus and pre-existing major macrovascular disease. Pioglitazone or placebo was added to existing antidiabetic and cardiovascular therapy for up to 3.5 years. This study showed an increase in reports of heart failure, however this did not lead to an increase in mortality in this study.  Caution should be exercised in patients over 75 years because of the limited experience in this patient group.

Weight gain:

In clinical trials with pioglitazone there was evidence of dose related weight gain, which may be due to fat accumulation and in some cases associated with fluid retention.  In some cases weight increase may be a symptom of cardiac failure, therefore weight should be closely monitored. Part of the treatment of diabetes is dietary control. Patients should be advised to adhere strictly to a calorie-controlled diet.

 Hypoglycaemia:

As a consequence of increased insulin sensitivity, patients receiving pioglitazone in dual or triple oral therapy with a sulphonylurea or in dual therapy with insulin may be at risk for dose-related hypoglycaemia, and a reduction in the dose of the sulphonylurea or insulin may be necessary.

4.8        Undesirable effects

 PIOGLITAZONE IN COMBINATION THERAPY WITH INSULIN

Metabolism and nutrition disorders

 Common:       hypoglycaemia

 General disorders and administration site conditions

 Very common: oedema

 Infections and infestations

 Common:       bronchitis

 Investigations

 Common:       weight increase

 Musculoskeletal system and connective tissue disorders

 Common:       back pain, arthralgia

 Respiratory, thoracic and mediastinal disorders

 Common:       dyspnoea

 Cardiac disorders

 Common:       heart failure

In controlled clinical trials the incidence of reports of heart failure with pioglitazone treatment was the same as in placebo, metformin and sulphonylurea treatment groups, but was increased when used in combination therapy with insulin. In an outcome study of patients with pre-existing major macrovascular disease, the incidence of serious heart failure was 1.6 % higher with pioglitazone than with placebo, when added to therapy that included insulin.  However, this did not lead to an increase in mortality in this study. Heart failure has been reported rarely with marketing use of pioglitazone, but more frequently when pioglitazone was used in combination with insulin or in patients with a history of cardiac failure.

5.      PHARMACOLOGICAL PROPERTIES

5.1   Pharmacodynamic properties

In a placebo controlled trial, patients with inadequate glycaemic control despite a three month insulin optimisation period were randomised to pioglitazone or placebo for 12 months. Patients receiving pioglitazone had a mean reduction in HbA1c of 0.45 % compared with those continuing on insulin alone, and a reduction of insulin dose in the pioglitazone treated group. 

In PROactive, a cardiovascular outcome study, 5238 patients with type 2 diabetes mellitus and pre-existing major macrovascular disease were randomised to pioglitazone or placebo in addition to existing antidiabetic and cardiovascular therapy, for up to 3.5 years. The study population had an average age of 62 years; the average duration of diabetes was 9.5 years. Approximately one third of patients were receiving insulin in combination with metformin and/or a sulphonylurea. To be eligible patients had to have had one or more of the following: myocardial infarction, stroke, percutaneous cardiac intervention or coronary artery bypass graft, acute coronary syndrome, coronary artery disease, or peripheral arterial obstructive disease. Almost half of the patients had a previous myocardial infarction and approximately 20% had had a stroke. Approximately half of the study population had at least two of the cardiovascular history entry criteria. Almost all subjects (95%) were receiving cardiovascular medications (beta blockers, ACE inhibitors, angiotensin II antagonists, calcium channel blockers, nitrates, diuretics, aspirin, statins, fibrates).

Although the study failed regarding its primary endpoint, which was a composite of all-cause mortality, non-fatal myocardial infarction, stroke, acute coronary syndrome, major leg amputation, coronary revascularisation and leg revascularisation, the results suggest that there are no long-term cardiovascular concerns regarding use of pioglitazone. However, the incidences of oedema, weight gain and heart failure were increased. No increase in mortality from heart failure was observed.

Updated on 02-Nov-2006 and displayed until 06-Feb-2007

Reasons for adding or updating:

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable Effects

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

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

 4.1    Therapeutic indications

 Pioglitazone is indicated in the treatment of type 2 diabetes mellitus:

as monotherapy

-         in patients (particularly overweight patients) inadequately controlled by diet and exercise for whom metformin is inappropriate because of contraindications or intolerance
 
 as dual oral therapy in combination with

-         metformin, in patients (particularly overweight patients) with insufficient glycaemic control despite maximal tolerated dose of monotherapy with metformin

-         a sulphonylurea, only in patients who show intolerance to metformin or for whom metformin is contraindicated, with insufficient glycaemic control despite maximal tolerated dose of monotherapy with a sulphonylurea.

 
 
as triple oral therapy in combination with

-         metformin and a sulphonylurea, in patients (particularly overweight patients) with insufficient glycaemic control despite dual oral therapy.

 4.5     Interaction with other medicinal products and other forms of interaction

Co-administration of pioglitazone with gemfibrozil (an inhibitor of cytochrome P450 2C8) is reported to result in a 3-fold increase in AUC of pioglitazone. Since there is a potential for an increase in dose-related adverse events, a decrease in the dose of pioglitazone may be needed when gemfibrozil is concomitantly administered.  Close monitoring of glycaemic control should be considered (see section 4.4).  Co-administration of pioglitazone with rifampicin (an inducer of cytochrome P450 2C8) is reported to result in a 54% decrease in AUC of pioglitazone. The pioglitazone dose may need to be increased when rifampicin is concomitantly administered.  Close monitoring of glycaemic control should be considered (see section 4.4).

4.8     Undesirable effects

Pioglitazone in triple oral combination therapy with metformin and sulphonylurea 

Investigations

 Common:         weight increased, blood creatine phosphokinase increased

 Metabolism and nutrition disorders

 Very common:  hypoglycaemia

 Musculoskeletal and connective tissue disorders

 Common:         arthralgia

Updated on 27-Oct-2006 and displayed until 02-Nov-2006

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.8 - Undesirable Effects
  • Change to section 7 - Marketing Authorisation Holder

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

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 4.4: Eye disorders warning has been entered:

Post-marketing reports of new-onset or worsening diabetic macular oedema with decreased visual acuity have been reported with thiazolidinediones, including pioglitazone. Many of these patients reported concurrent peripheral oedema. It is unclear whether or not there is a direct association between pioglitazone and macular oedema but prescribers should be alert to the possibility of macular oedema if patients report disturbances in visual acuity; an appropriate ophthalmological referral should be considered.

Section 4.8: Undesirable effects Eye disorders has been entered

Macular oedema:          not known

Section 7. Update to Marketing Authorisation Holder address has been entered:

Takeda Global Research and Development Centre (Europe) Ltd
Arundel Great Court
2 Arundel Street
London
WC2R 3DA
United Kingdom

Updated on 02-Feb-2006 and displayed until 27-Oct-2006

Reasons for adding or updating:

  • Change to section 9 - Date of Renewal of Authorisation
  • Change to section 10 (date of (partial) revision of the text

Updated on 30-Sep-2005 and displayed until 02-Feb-2006

Reasons for adding or updating:

  • Removal of Black Triangle

Updated on 27-May-2005 and displayed until 30-Sep-2005

Reasons for adding or updating:

  • Change to section 4.4 - Special Warnings and Precautions for Use
  • Change to section 5.1 - Pharmacodynamic Properties

Updated on 06-May-2005 and displayed until 09-May-2005

Reasons for adding or updating:

  • Change to section 4.4 - Special Warnings and Precautions for Use
  • Change to section 5.1 - Pharmacodynamic Properties
  • Pending awaiting re-submission

Updated on 11-Nov-2003 and displayed until 06-May-2005

Reasons for adding or updating:

  • Change to section 2 - qualitative and quantitative composition
  • Change to section 3 - pharmaceutical form
  • Change to section 8 - MA number
  • Change to section 10 (date of (partial) revision of the text

Updated on 26-Sep-2003 and displayed until 11-Nov-2003

Reasons for adding or updating:

  • Change to section 2 - qualitative and quantitative composition
  • Change to section 3 - pharmaceutical form
  • Change to section 10 (date of (partial) revision of the text

Updated on 04-Sep-2003 and displayed until 26-Sep-2003

Reasons for adding or updating:

  • 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 4.6 - Pregnancy and Lactation
  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 (date of (partial) revision of the text

Updated on 03-Sep-2003 and displayed until 04-Sep-2003

Reasons for adding or updating:

  • 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 4.6 - Pregnancy and Lactation
  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 (date of (partial) revision of the text

Updated on 03-Jun-2003 and displayed until 03-Sep-2003

Reasons for adding or updating:

  • Change to section 4.2 - Posology and Method of Administration
  • Change to section 10 (date of (partial) revision of the text

Updated on 30-Jul-2002 and displayed until 03-Jun-2003

Reasons for adding or updating:

  • Change to section 5.1 - Pharmacodynamic Properties

Updated on 24-Jul-2001 and displayed until 30-Jul-2002

Reasons for adding or updating:

  • Change to section 1 - trade name

Updated on 13-Mar-2001 and displayed until 24-Jul-2001

Reasons for adding or updating:

  • No reasons supplied

Updated on 22-Jan-2001 and displayed until 13-Mar-2001

Reasons for adding or updating:

  • No reasons supplied

Company contact details

Takeda UK Ltd

Company image
Address

Building 3, Glory Park Avenue, Wooburn Green, High Wycombe, HP10 0DF

Fax

+44 (0)1628 526 615

Medical Information e-mail
Telephone

+44 (0)1628 537 900

Medical Information Direct Line

+44 (0)1628 537 900

Before you contact this company: often several companies will market medicines with the same active ingredient. Please check that this is the correct company before contacting them. Why?

Active ingredients

pioglitazone hydrochloride

Legal categories

POM - Prescription Only Medicine

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