Competact 15 mg/850 mg film-coated Tablets

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Summary of Product Characteristics last updated on medicines.ie: 18/10/2018

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Takeda Products Ireland Ltd

Takeda Products Ireland Ltd

Company Products

Medicine NameActive Ingredients
Medicine Name Actos tablets Active Ingredients pioglitazone hydrochloride
Medicine Name Adcetris 50 mg powder for concentrate for solution for infusion Active Ingredients Brentuximab vedotin
Medicine Name Alofisel 5 million cells/mL suspension for injection Active Ingredients Human Allogeneic Mesenchymal Adult Stem Cells
Medicine Name Alunbrig Active Ingredients Brigatinib
Medicine Name Blopress Plus Tablets Active Ingredients Candesartan Cilexetil, Hydrochlorothiazide
Medicine Name Blopress tablets Active Ingredients Candesartan Cilexetil
Medicine Name Calcichew 500mg Chewable Tablets Active Ingredients Calcium Carbonate
Medicine Name Calcichew-D3 Forte Chewable Tablets Active Ingredients Calcium Carbonate, Colecalciferol (Vitamin D3)
Medicine Name Calcichew-D3 Forte Double Strength 1000 mg/800 IU chewable tablets Active Ingredients Calcium Carbonate, Colecalciferol (Vitamin D3)
Medicine Name Competact 15 mg/850 mg film-coated Tablets Active Ingredients Metformin Hydrochloride, pioglitazone hydrochloride
Medicine Name Condyline Cutaneous Solution 5 mg/ml Active Ingredients Podophyllotoxin
Medicine Name Edarbi Tablets Active Ingredients Azilsartan medoxomil potassium
Medicine Name Entyvio 300 mg powder for concentrate for solution for infusion Active Ingredients Vedolizumab
Medicine Name Instanyl 50, 100 and 200 mcg nasal spray, solution in single-dose container Active Ingredients fentanyl citrate
Medicine Name Matrifen Transdermal patch Active Ingredients Fentanyl
Medicine Name Mepact 4mg powder for suspension for infusion Active Ingredients Mifamurtide
Medicine Name Midon 2.5 mg Tablets Active Ingredients Midodrine Hydrochloride
Medicine Name Midon 5 mg Tablets Active Ingredients Midodrine Hydrochloride
Medicine Name NINLARO 2.3 mg, 3 mg, 4 mg hard capsules Active Ingredients Ixazomib Citrate
Medicine Name Prostap 3 DCS Active Ingredients Leuprorelin Acetate
Medicine Name Prostap 6 DCS Active Ingredients Leuprorelin Acetate
Medicine Name Prostap SR DCS Active Ingredients Leuprorelin Acetate
Medicine Name Protium 20mg Active Ingredients Pantoprazole sodium sesquihydrate
Medicine Name Protium 40mg Active Ingredients Pantoprazole sodium sesquihydrate
Medicine Name Protium 40mg iv Active Ingredients Pantoprazole sodium sesquihydrate
1 - 0 of 26 items.Total: Infinity pages

When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 18 October 2018 SmPC

Reasons for updating

  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

A variation to update the Competact SmPC and PIL was recently approved.  The application sought to add the unique product identifier data to the labelling (needed as a result of FMD) and as part of the submission, minor corrections to typos and formatting were also made. 

Updated on 6 April 2017 SmPC

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 6 April 2017 SmPC

Reasons for updating

  • 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 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Change to section

Details of change

4.2 Posology and method of administration

Text in red added and text in blue removed:

 

Posology

 

Adults with normal renal function (GFR ≥ 90 mL/min)

 

The recommended dose of Competact is 30 mg/day pioglitazone plus 1700 mg/day of metformin hydrochloride (this dose is achievable with one tablet of Competact 15 mg/850 mg, taken twice a day).

 

 

Renal impairment

Competact should not be used in patients with renal failure or renal dysfunction (creatinine clearance< 60 ml/min) (see sections 4.3 and 4.4).

A GFR should be assessed before initiation of treatment with metformin containing products and at least annually thereafter. In patients at increased risk of further progression of renal impairment and in the elderly, renal function should be assessed more frequently, e.g. every 3‑6 months.

 

The maximum daily dose of metformin should preferably be divided into 2‑3 daily doses. Factors that may increase the risk of lactic acidosis (see section 4.4) should be reviewed before considering initiation of metformin in patients with GFR < 60 mL/min.

If no adequate strength of Competact is available, individual monocomponents should be used instead of the fixed dose combination.

 

GFR mL/min

            

Metformin

Pioglitazone

60‑89

Maximum daily dose is 3000 mg.

Dose reduction may be considered in relation to declining renal function.

 

 

 

No dose adjustment.

Maximum daily dose is 45 mg

 

 

45‑59

Maximum daily dose is 2000 mg.

The starting dose is at most half of the maximum dose.

30‑44

Maximum daily dose is 1000 mg.

The starting dose is at most half of the maximum dose.

< 30

Metformin is contra‑indicated

 

Hepatic impairment

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

...

 

4.3 Contraindications

Text in red added and text in blue removed:

 

Competact is contraindicated in patients with:

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1

- Cardiac failure or history of cardiac failure (NYHA stages I to IV)

- Current bladder cancer or a history of bladder cancer

- Uninvestigated macroscopic haematuria

- Acute or chronic disease which may cause tissue hypoxia such as cardiac or respiratory failure, recent myocardial infarction, shock

- Hepatic impairment

- Acute alcohol intoxication, alcoholism

- Diabetic ketoacidosis or Any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis)

- Ddiabetic pre-coma

- Severe rRenal failure or renal dysfunction (creatinine clearance GFR < 3060 mlL/min) (see section 4.4).

- Acute conditions with the potential to alter renal function such as:

- Dehydration

- Severe infection

- Shock

- Intravascular administration of iodinated contrast agents (see section 4.4)

- Breast-feeding (see section 4.6)

 

4.4  Special warnings and precautions for use

Text in red added and text in blue removed:

 

There is no clinical experience of pioglitazone in triple combination with other oral antidiabetic medicinal products.

 

Lactic acidosis

Lactic acidosis is a very rare, but serious, metabolic complication that can occur due to metformin accumulation. Reported cases of lactic acidosis in patients on metformin have occurred primarily in diabetic patients with significant renal failure. The incidence of lactic acidosis can and should be reduced by assessing also other associated risk factors such as poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol intake, hepatic insufficiency and any condition associated with hypoxia.

 

Lactic acidosis is characterised by acidotic dyspnoea, abdominal pain and hypothermia followed by coma. Diagnostic laboratory findings are decreased blood pH, plasma lactate levels above 5 mmol/L, and an increased anion gap and lactate/pyruvate ratio. If metabolic acidosis is suspected, treatment with the medicinal product should be discontinued and the patient hospitalised immediately (see section 4.9).

Lactic acidosis, a very rare but serious metabolic complication, most often occurs at acute worsening of renal function or cardiorespiratory illness or sepsis. Metformin accumulation occurs at acute worsening of renal function and increases the risk of lactic acidosis.

 

In case of dehydration (severe diarrhoea or vomiting, fever, heat, reduced fluid intake), Competact should be temporarily discontinued and contact with a health care professional is recommended.

 

Medicinal products that can acutely impair renal function (such as antihypertensives, diuretics and NSAIDs) should be initiated with caution in metformin treated patients. Other risk factors for lactic acidosis are excessive alcohol intake, hepatic insufficiency, inadequately controlled diabetes, ketosis, prolonged fasting and any conditions associated with hypoxia, as well as concomitant use of medicinal products that may cause lactic acidosis (see sections 4.3 and 4.5).

 

Patients and/or care-givers should be informed on the risk of lactic acidosis. Lactic acidosis is characterised by acidotic dyspnoea, abdominal pain, muscle cramps, asthenia and hypothermia followed by coma. In case of suspected symptoms, the patient should stop taking Competact and seek immediate medical attention. Diagnostic laboratory findings are decreased blood pH (< 7.35), increased plasma lactate levels (> 5 mmol/l) and an increased anion gap and lactate/pyruvate ratio.

 

Renal function

 

GFR should be assessed before treatment initiation and regularly thereafter, see section 4.2. Metformin is contraindicated in patients with GFR<30 mL/min and should be temporarily discontinued in the presence of conditions that alter renal function ,see sections 4.3.

As metformin is excreted by the kidney, serum creatinine concentrations should be determined regularly:

- at least once a year in patients with normal renal function

- at least two to four times a year in patients with serum creatinine levels at the upper limits of normal and in elderly subjects

 

Decreased renal function in elderly patients is frequent and asymptomatic. Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive therapy or diuretic therapy and when starting treatment with a NSAID.

 

Surgery

 

As Competact contains metformin hydrochloride, the treatment should be discontinued 48 hours before elective surgery with general anaesthesia and should not be usually resumed earlier than 48 hours afterwards it must be discontinued at the time of surgery under general, spinal or epidural anesthesia. Therapy may be restarted no earlier than 48 hours following surgery or resumption of oral nutrition and provided that renal function has been re‑evaluated and found to be stable. 

 

Administration of iodinated contrast agent

 

The intravascular administration of iodinated contrast agents in radiological studies can lead to renal failure. Therefore, due to the metformin active substance, Competact should be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal (see section 4.5).

Intravascular administration of iodinated contrast agents may lead to contrast induced nephropathy, resulting in metformin accumulation and an increased risk of lactic acidosis. Competact should be discontinued prior to or at the time of the imaging procedure and not restarted until at least 48 hours after, provided that renal function has been re-evaluated and found to be stable, see sections 4.2 and 4.5.

...

 

4.5       Interaction with other medicinal products and other forms of interaction

 

Text in red added and text in blue removed:

 

There have been no formal interaction studies for Competact. The following statements reflect the information available on the individual active substances (pioglitazone and metformin).

 

Metformin

 

Concomitant use not recommended

 

Alcohol

Alcohol intoxication is associated with an increased risk of lactic acidosis, particularly in case of fasting, malnutrition or hepatic impairment.

 

Iodinated contrast agents

Competact must be discontinued prior to or at the time of the imaging procedure and not restarted until at least 48 hours after, provided that renal function has been re‑evaluated and found to be stable, see sections 4.2 and 4.4.

Intravascular administration of iodinated contrast agents in radiological studies may lead to renal failure, resulting in metformin accumulation and risk of lactic acidosis. Metformin should be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal.

 

There is increased risk of lactic acidosis in acute alcohol intoxication (particularly in the case of fasting, malnutrition or hepatic insufficiency) due to the metformin active substance of Competact (see section 4.4). Avoid consumption of alcohol and medicinal products containing alcohol.

 

Combinations requiring precautions for use

Some medicinal products that can adversely affect renal function which may increase the risk of lactic acidosis, e.g. NSAIDS, including selective cyclo-oxygenase (COX) II inhibitors, ACE inhibitors, angiotensin II receptor antagonists and diuretics, especially loop diuretics. When starting or using such products in combination with Competact, close monitoring of renal function is necessary.

 

Cationic medicinal products that are eliminated by renal tubular secretion (e.g. cimetidine) may interact with metformin by competing for common renal tubular transport systems. A study conducted in seven normal healthy volunteers showed that cimetidine, administered as 400 mg twice daily, increased metformin systemic exposure (AUC) by 50% and Cmax by 81%. Therefore, close monitoring of glycaemic control, dose adjustment within the recommended posology and changes in diabetic treatment should be considered when cationic medicinal products that are eliminated by renal tubular secretion are co-administered

 

10. Date of revision of the text

Updated text in red:

 

12th Dec 2016

Updated on 23 January 2017 PIL

Reasons for updating

  • New PIL for new product

Updated on 23 January 2017 PIL

Reasons for updating

  • Change to section 6 - manufacturer

Updated on 20 December 2016 PIL

Reasons for updating

  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 3 - dose and frequency
  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 14 November 2016 PIL

Reasons for updating

  • Change to section 6 - manufacturer
  • Change to section 6 - date of revision

Updated on 13 June 2016 SmPC

Reasons for updating

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

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Minor addition to Setion 4.8

Text in red has been added


...

6 A pooled analysis was conducted of adverse reactions of bone fractures from randomised, comparator controlled, double blind clinical trials in over 8,100 patients in the pioglitazone‑treated groups and 7,400 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%).

In the 3.5 year 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. The observed excess risk of fractures for women on pioglitazone in this study is therefore 0.5 fractures per 100 patient years of use. No increase in fracture rates was observed in men treated with pioglitazone (1.7%) versus comparator (2.1%). Post-marketing, bone fractures have been reported in both male and female patients (see section 4.4).

 

7 In active comparator controlled trials oedema was reported in 6.3% of patients treated with metformin and pioglitazone, whereas the addition of sulphonylurea to metformin treatment resulted in oedema in 2.2% of patients. The reports of oedema were generally mild to moderate and usually did not require discontinuation of treatment.
...

 

Updated on 9 June 2016 PIL

Reasons for updating

  • Change to side-effects
  • Change to date of revision

Updated on 13 May 2016 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Change to section

Details of change

4.4 Special warnings and precautions for use

Text in red added and text in blue removed:

 

Bladder cancer

Cases of bladder cancer were reported more frequently in a meta-analysis of controlled clinical trials with pioglitazone (19 cases from 12,506 patients, 0.15%) than in control groups (7 cases from 10,212 patients, 0.07%) HR=2.64 (95% CI 1.11-6.31, 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 Eepidemiological data studies have also suggested a small increased risk of bladder cancer in diabetic patients treated with pioglitazone, although not all studies identified a statistically significant increased risk 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.

 

...

10. Date of revision of the text

Updated text in red:

 

28th April 2016

Updated on 29 April 2016 SmPC

Reasons for updating

  • 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 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 6.1 - List of excipients
  • Change to section 6.5 - Nature and contents of container
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Change to section

Details of change

 

There have been minor formatting amendments

4.3 Contraindications

Text in red added:

- Dehydration

- Severe infection

- Shock

- Intravascular administration of iodinated contrast agents (see section 4.4)

- Breast-feeding (see section 4.6)

4.4 Special warnings and precautions for use

Text in blue removed and text in red added:

...

Others

An increased incidence in bone fractures in women was seen in a pooled analysis of adverse reactions 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. (see section 4.8)

 

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 observed excess risk of fractures for women on pioglitazone in this study is therefore 0.5 fractures per 100 patient years of use.

 

Some epidemiological studies have suggested a similarly increased risk of fracture in both men and women. The risk of fractures should be considered in the long term care of patients treated with pioglitazone (see section 4.8).

 

Pioglitazone should be used with caution during concomitant administration of cytochrome P450 2C8 inhibitors (e.g. gemfibrozil) or inducers (e.g. rifampicin). Glycaemic control should be monitored closely. Pioglitazone dose adjustment within the recommended posology or changes in diabetic treatment should be considered (see section 4.5).

4.8 Undesirable effects

Text in blue removed and text in red added:

 

Summary of the safety profile

Clinical trials have been conducted with Competact tablets and co-administered pioglitazone and metformin (see section 5.1). Bioequivalence of Competact with co-administered pioglitazone and metformin has also been demonstrated (see section 5.2). At the initiation of the treatment abdominal pain, diarrhoea, loss of appetite, nausea and vomiting may occur, these reactions are very common but usually disappear spontaneously in most cases. Lactic acidosis is a serious reaction which may occur very rarely (< 1/10,000) (see section 4.4) and other reactions such as bone fracture, weight increase and oedema may occur commonly (≥ 1/100 to < 1/10) (see section 4.4).

 

6 A pooled analysis was conducted of adverse reactions 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%).

In the 3.5 year 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. The observed excess risk of fractures for women on pioglitazone in this study is therefore 0.5 fractures per 100 patient years of use. No increase in fracture rates was observed in men treated with pioglitazone (1.7%) versus comparator (2.1%) (see section 4.4).

4.9 Overdose

Text in blue removed

No data are available with regard to overdose of Competact.

 

In clinical studies, patients have taken pioglitazone at higher than the recommended highest dose of 45 mg daily. The maximum reported dose of 120 mg/day for four days, then 180 mg/day for seven days was not associated with any symptoms.

5.1 Pharmacodynamic Properties

Text in blue removed and text in red added:

 

Competact combines two antihyperglycaemic active substances with complementary mechanisms of action to improve glycaemic control in patients with type 2 diabetes mellitus: pioglitazone, a member of the thiazolidinedione class and metformin hydrochloride, a member of the biguanide class. Thiazolidinediones act primarily by reducing insulin resistance and biguanides act primarily by decreasing endogenous hepatic glucose production.

 

Pioglitazone and metformin combination

 

The fixed dose combination tablet of pioglitazone 15 mg/metformin 850 mg BID (N=201), pioglitazone 15 mg BID (N=189), and metformin 850 mg BID (N=210) were evaluated in type 2 diabetes mellitus patients with mean baseline HbA1c of 9.5% in a randomised double-blind, parallel-group study. Previous anti-diabetic medicinal products medication was were discontinued for 12 weeks prior to baseline measurements. After 24 weeks of treatment, the primary endpoint of mean change from baseline in HbA1c was -1.83% in the combination group versus -0.96% in the pioglitazone group (p< 0.0001) and -0.99% in the metformin group (p< 0.0001).

 

The prospective randomised (UKPDS) study has established the long-term benefit of intensive blood glucose control in type 2 diabetes mellitus. Analysis of the results for overweight patients treated with metformin after failure of diet alone showed:

 

- a significant reduction of the absolute risk of any diabetes-related complication in the metformin group (29.8 events/1,000 patient-years) versus diet alone (43.3 events/1,000 patient-years), p=0.0023, and versus the combined sulphonylurea and insulin monotherapy groups (40.1 events/1,000 patient-years), p=0.0034

5.3 Preclinical safety data

Text in blue removed

 

...

Metformin

Preclinical data for metformin reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction.

 

Environmental Risk Assessment (ERA)

No environmental impact is anticipated from the clinical use of pioglitazone.

6.1 List of excipients

Text in red added:

 

Film coat

Hypromellose

Macrogol 8000

Talc

Titanium dioxide (E171).

6.5 Nature and contents of container

Text in blue removed and text in red added:

 

Aluminium/aluminium blisters.,

Ppacks of 14, 28, 30, 50, 56, 60, 90, 98, 112, 180.,

Multipack of 196 (2 packs of x 98) tablets and or 60 x 1 tablets in aluminium/aluminium perforated unit dose blisters in pack of 60 x 1 tablets.

 

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Text in blue removed and text in red added:

 

No special requirements. for disposal.

10. Date of revision of the text

Updated text in red:

 

25th April 2016

Updated on 28 April 2016 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change of contraindications
  • Change to instructions about overdose
  • Change to side-effects
  • Change to information about drinking alcohol
  • Change to information about pregnancy or lactation
  • Change to date of revision
  • Change to appearance of the medicine

Updated on 5 August 2014 PIL

Reasons for updating

  • Change to MA holder contact details
  • Change to improve clarity and readability
  • Addition of information on reporting a side effect.

Updated on 5 August 2014 SmPC

Reasons for updating

  • Change to section 10 - Date of revision of the text
  • Change to MA holder contact details
  • Change to improve clarity and readability
  • Change to Section 4.8 – Undesirable effects - how to report a side effect

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Change to section

Details of change

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Changed:

‘‘For a full list of excipients’’

 

to

 

‘’For the full list of excipients’’

 

4.2. Posology and method of administration

Changed:

The usual dose....

 

to

 

The recommended dose.....

 

Formatting of headings

4.3. Contraindications

Added:

‘’Hypersensitivity to the active substance or to any of the excipients listed in section 6.1’’

 

4.4.  Special warnings and precautions for use

 

Formatting of headings

Changed:

“Bladder”

 

to

 

“Bladder cancer”

4.6 Fertility, pregnancy and lactation

Formatting of headings

4.8. Undesirable effects

Formatting of table and Changed:

 

“in less than 1 case per 10,000 patients”

 

To

 

“very rarely (< 1/10,000)”

 

“in less than 1 case per 10 patients”

 

To

 

“commonly (≥ 1/100 to < 1/10)”

 

“Within each frequency grouping, adverse reactions are presented in order of decreasing incidence and seriousness”

 

To

 

“Within each system organ class, adverse reactions are presented in order of decreasing incidence followed by decreasing seriousness.”

 

 

Addition of

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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

 

5.1. Pharmacodynamic properties

Formatting of headings

5.2     Pharmacokinetic properties

Formatting of headings

5.3 Preclinical safety data

Changed:

 

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

 

To

 

Environmental Risk Assessment (ERA)

No environmental impact is anticipated from the clinical use of pioglitazone.”

7.

Changed:

 

“Takeda Pharma A/S

Langebjerg 1

DK-4000 Roskilde

Denmark”

 

to

 

“Takeda Pharma A/S

Dybendal Alle 10

2630 Taastrup

Denmark”

 

10. DATE OF REVISION OF THE TEXT

 

Changed to:

 

23/07/2014

 

Updated on 29 November 2013 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects

Legal category: Product subject to medical prescription which may be renewed (B)

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, (but) and more frequently when pioglitazone was used in combination with insulin or in patients with a history of cardiac failure.

 

Updated on 29 November 2013 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change of distributor details

Updated on 16 May 2013 PIL

Reasons for updating

  • Change to marketing authorisation holder

Updated on 16 May 2013 SmPC

Reasons for updating

  • Change to section 7 - Marketing authorisation holder

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

The SmPC 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 January 2013 PIL

Reasons for updating

  • Change to side-effects

Updated on 10 January 2013 SmPC

Reasons for updating

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

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Addtional information added to sections 4.8
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 26 January 2012 SmPC

Reasons for updating

  • Correction of spelling/typing errors

Legal category: Product subject to medical prescription which may be renewed (B)

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section 10 of Url link missing 'u' at end.

Updated on 20 January 2012 PIL

Reasons for updating

  • Change to side-effects

Updated on 19 January 2012 SmPC

Reasons for 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

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4.1. Therapeutic indications -Competact

is indicated as second line treatment

of type 2 diabetes mellitus adult paitents. 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).
Adde
d,





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 age‐ related 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 1.11‐6.31, 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 20 July 2011 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change of contraindications
  • Change to date of revision

Updated on 20 July 2011 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • 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 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Most of the changes do not alter the meaning of the licence and are either rewording, re-positioning or re-formatting of the previous text.

The updated Competact  SmPC contains additional information to the following sections:

 

Updated SmPC wording (main changes to be aware of)

Summary of change

4.4 Special Warnings and Precautions for use

Monitoring of liver function

 

Addition of elevated liver enzymes and that there have been some fatal reports.

4.7       Effects on ability to drive and use machines

 

Competact 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.

Following wording has been added, previous wording was ’ No effects on ability to drive and use machines have been observed.’

4.8     Undesirable effects

 

          At the initiation of the treatment abdominal pain, diarrhoea, loss of appetite, nausea and vomiting may occur, these reactions are very common but usually disappear spontaneously in most cases. Lactic acidosis is a serious reaction which may occur in less than 1 case per 10,000 patients (see section 4.4) and other reactions such as bone fracture, weight increase and oedema may occur in less than 1 case per 10 patients (see section 4.4).

No new events have been reported, but the information is now presented in a table and the following wording added to introduction of section

5.1 Pharmacodynamic properties

 

Paediatric population

The European Medicines Agency has waived the obligation to submit the results of studies with Competact in all subsets of the paediatric population in Type 2 Diabetes Mellitus. See section 4.2 for information on paediatric use.

 

Following wording has been added

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 28 April 2010 PIL

Reasons for updating

  • Change to marketing authorisation holder

Updated on 21 April 2010 SmPC

Reasons for updating

  • Change to section 5.3 - Preclinical safety data

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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 30 October 2009 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company



The following information has been added to the sections listed below;

 

Section 4. 8. Undesirable effects-''

Clinical trials have been conducted with Competact tablets and co-administered pioglitazone and metformin (see section 5.1). Bioequivalence of Competact with co-administered pioglitazone and metformin has also been demonstrated (see section 5.2).’’

 

 
Section 5.1          Pharmacodynamic properties

‘’Pioglitazone and metformin combination

The fixed dose combination tablet of pioglitazone 15 mg/metformin 850 mg BID (N=201), pioglitazone 15 mg BID (N=189), and metformin 850 mg BID (N=210) were evaluated in type 2 diabetes mellitus patients with mean baseline HbA1C of 9.5% in a randomised double-blind, parallel-group study. Previous anti-diabetic medication was discontinued for 12 weeks prior to baseline measurements. After 24 weeks of treatment, the primary endpoint of mean change from baseline in HbA1c was -1.83% in the combination group versus -0.96% in the pioglitazone group (p<0.0001) and -0.99% in the metformin group (p<0.0001).

The safety profile seen in this study reflected the known adverse reactions seen with the individual products and did not suggest any new safety issues.’’

Updated on 12 May 2009 SmPC

Reasons for updating

  • Change to marketing authorisation holder address

Legal category: Product subject to medical prescription which may be renewed (B)

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7.       MARKETING AUTHORISATION HOLDER

 

Takeda Global Research and Development Centre (Europe) Ltd

61 Aldwych

London WC2B 4AE

United Kingdom

Updated on 12 May 2009 PIL

Reasons for updating

  • Change to marketing authorisation holder address

Updated on 12 November 2007 SmPC

Reasons for updating

  • Change to section 4.3 - Contraindications
  • Change to section 5.1 - Pharmacodynamic properties

Legal category: Product subject to medical prescription which may be renewed (B)

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Section 4.3
removal of the insulin contraindication
 
Section 5.1

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 eligibile 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 incidence of oedema, weight gain and heart failure were increased.  No increase in mortality from heart failure was observed.

Updated on 12 November 2007 PIL

Reasons for updating

  • Change of contraindications

Updated on 11 October 2007 PIL

Reasons for updating

  • Change to side-effects

Updated on 6 September 2007 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects

Legal category: Product subject to medical prescription which may be renewed (B)

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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%).

 

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

Updated on 28 August 2007 PIL

Reasons for updating

  • New PIL for new product

Updated on 2 April 2007 SmPC

Reasons for updating

  • New SPC for new product

Legal category: Product subject to medical prescription which may be renewed (B)