Last Updated on eMC 12-07-2018 View medicine  | 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.

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 9 - Date of first authorisation/renewal of the authorisation
  • Change to section 10 - Date of revision of the text
  • Removal of black triangle

Date of revision of text on the SPC:24-05-2018

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Key Changes to this SmPC have been summarised in the table below:

SmPC Section Updated

Changes

 

Removal of Black Triangle.

4.2, 4.4, 4.5, 4.8, 5.1, 5.2

Re-formatting of text within these sections

4.8

Following text has been added:

 

Acute pancreatitis is a serious adverse reaction and is attributed to the alogliptin component of Vipdomet (see section 4.4). Hypersensitivity reactions, including Stevens-Johnson syndrome, anaphylactic reactions, and angioedema are serious and are attributed to the alogliptin component of Vipdomet (see section 4.4). Lactic acidosis is a serious adverse reaction, which may occur very rarely (<1/10,000), and is attributed to the metformin component of Vipdomet (see section 4.4). Other reactions such as upper respiratory tract infections, nasopharyngitis, headache, gastroenteritis, abdominal pain, diarrhoea, vomiting, gastritis, gastroesophageal reflux disease, pruritus, rash, hypoglycaemia may occur commonly (≥ 1/100 to < 1/10) (see section 4.4) which are attributed to Vipdomet

 

 

Following text has been deleted:

 

The safety profile of co‑administered alogliptin and metformin was consistent with that of the individual components as demonstrated in clinical trials for alogliptin and from the comprehensive data available for metformin. As such, the following section outlines the adverse reactions of the individual components of Vipdomet (alogliptin/metformin) as reported in their respective Summary of Product Characteristics.

 

Alogliptin

 

The information provided is based on a total of 9,405patients with type2 diabetes mellitus, including 3,750patients treated with 25mg alogliptin and 2,476patients treated with 12.5mg alogliptin, who participated in one phase2 or 12phase3 double‑blind, placebo- or active‑controlled clinical studies. In addition, a cardiovascular outcomes study with 5,380patients with type2 diabetes mellitus and a recent acute coronary syndrome event was conducted with 2,701 randomised to alogliptin and 2,679 randomised to placebo. These studies evaluated the effects of alogliptin on glycaemic control and its safety as monotherapy, as initial combination therapy with metformin or a thiazolidinedione, and as add‑on therapy to metformin, or a sulphonylurea, or a thiazolidinedione (with or without metformin or a sulphonylurea), or insulin (with or without metformin).

 

In a pooled analysis of the data from 13studies, the overall incidences of adverse events, serious adverse events and adverse events resulting in discontinuation of therapy were comparable in patients treated with 25mg alogliptin, 12.5mg alogliptin, active‑control or placebo. The most common adverse reaction in patients treated with 25mg alogliptin was headache.

 

The safety of alogliptin between the elderly (≥65years old) and non‑elderly (<65years old) was similar.

 

Adverse events tables 1,2,3,4 have been re-formatted and combined to create 1 table.

 

Addition of following text under Adverse event reporting:

 

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the GooglePlay or Apple App Store.

 

Sections 9 and 10

Date in both sections updated to 24th May 2018

 

Reasons for adding or updating:

  • Change to section 1 - Name of the medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • 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

Date of revision of text on the SPC:12-12-2016

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



Change to section

Details of change

1.       Name of the Medicinal Product

Text in red added and text in blue removed:

 

Vipdomet 12.5 mg/850 mg film‑coated tablets

Vipdomet 12.5 mg/1000 mg film-coated tablets

 

2.       Qualitative and Quantitative Composition

Text in red added and text in blue removed:

 

Vipdomet 12.5 mg/850 mg film‑coated tablets

Each tablet contains alogliptin benzoate equivalent to 12.5 mg alogliptin and 850 mg metformin hydrochloride.

 

Vipdomet 12.5 mg/1000 mg film coated tablets

Each tablet contains alogliptin benzoate equivalent to 12.5 mg alogliptin and 1000 mg metformin hydrochloride.

 

For the full list of excipients, see section 6.1.

 

3.       Pharmaceutical Form

Text in red added and text in blue removed:

 

Film-coated tablet (tablet).

 

Vipdomet 12.5 mg/850 mg film‑coated tablets

Light yellow, oblong (approximately 21.0 mm long by 10.1 mm wide), biconvex, film‑coated tablets with “12.5/850” debossed on one side and “322M” debossed on the other side.

 

Vipdomet 12.5 mg/1000 mg film coated tablets

Pale yellow, oblong (approximately 22.3 mm long by 10.7 mm wide), biconvex, film-coated tablets with “12.5/1000” debossed on one side and “322M” debossed on the other side.

 

4.2   Posology and method of administration

Text in red added and text in blue removed:

 

Adults (≥ 18 years old) with normal renal function (GFR 90 mL/min)

 

The dose of Vipdomet should be individualised on the basis of the patient’s current treatment regimen.

 

Special populations

 

Elderly (≥ 65 years old)

No dose adjustment is necessary based on age. However, dosing of alogliptin should be conservative in patients with advanced age due to the potential for decreased renal function in this population

 

Renal impairment

For patients with mild renal impairment (creatinine clearance ≥ 60 mL/min), no dose adjustment of Vipdomet is necessary (see section 5.2).

 

As Vipdomet contains metformin, it must not be used in patients with moderate or severe renal impairment or end-stage renal disease requiring dialysis (creatinine clearance < 60 mL/min) (see sections 4.3, 4.4 and 5.2).

 

Appropriate assessment of renal function is recommended prior to initiation of Vipdomet and at regular intervals thereafter (see section 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 Vipdomet is available, individual monocomponents should be used instead of the fixed dose combination.

 

GFR mL/min

Metformin

Alogliptin*

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 25 mg

45‑59

Maximum daily dose is 2000 mg

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

Maximum daily dose is 12.5 mg

30‑44

Maximum daily dose is 1000 mg.

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

Maximum daily dose is 12.5 mg

< 30

Metformin is contra‑indicated

Maximum daily dose is 6.25 mg

* Alogliptin dose adjustment is based on a pharmacokinetic study where kidney function was assessed using creatinine clearance levels estimated from the Cockcroft‑Gault equation.

 

4.3 Contraindications

Text in red added and text in blue removed:

 

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1 or history of a serious hypersensitivity reaction, including anaphylactic reaction, anaphylactic shock, and angioedema, to any dipeptidyl-peptidase-4 (DPP-4) inhibitor (see sections 4.4 and 4.8)

Any type of acute metabolic acidosis (such as lactic acidosis, Ddiabetic ketoacidosis)

·         dDiabetic pre-coma

Moderate and sSevere renal failure impairment and end-stage renal disease (creatinine clearance GFR < 60 30 mL/min; see section 4.4)

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

o dehydration

o severe infection

o shock

• Acute or chronic disease which may cause tissue hypoxia (see section 4.4) such as:

o cardiac or respiratory failure

o recent myocardial infarction

o shock

• Hepatic impairment (see section 4.4)

• Acute alcohol intoxication, alcoholism (see sections 4.4 and 4.5)

 

4.4 Special warnings and precautions for use

Text in red added and text in blue removed:

 

General

Vipdomet should not be used in patients with type 1 diabetes mellitus. Vipdomet is not a substitute for insulin in insulin-requiring patients.

 

Lactic acidosis

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) Vipdomet 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 Vipdomet 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.

Lactic acidosis is a very rare, but serious (high mortality in the absence of prompt treatment), 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 also assessing other associated risk factors such as poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol intake, hepatic impairment and any conditions associated with hypoxia.

 

Diagnosis

A diagnosis of lactic acidosis must be considered in the event of non-specific symptoms such as muscle cramps and/or abdominal pain and/or severe asthenia. Lactic acidosis is further characterised by acidotic dyspnoea and hypothermia followed by coma. Diagnostic laboratory findings are decreased blood pH, plasma lactate levels above 5 mmol/L, an increased anion gap and lactate/pyruvate ratio. If metabolic acidosis is suspected, treatment with Vipdomet should be discontinued and the patient hospitalised immediately (see section 4.9).

 

Administration of iodinated contrast agents

Intravascular administration of iodinated contrast media may lead to contrast induced nephropathy, resulting in metformin accumulation and an increased risk of lactic acidosis. Vipdomet 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.

 

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 section 4.3).

Alogliptin and metformin are substantially excreted by the kidney. The risk of metformin-related lactic acidosis increases with the degree of renal impairment, therefore, serum creatinine concentrations should be determined (and corresponding estimated glomerular filtration rate or creatinine clearance estimated) before initiating treatment and regularly thereafter:

• 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 limit of normal and in elderly patients

 

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 or diuretic therapy or when starting treatment with a nonsteroidal anti-inflammatory drug (NSAID).

 

Vipdomet is not recommended for use in patients with moderate and severe renal impairment and end-stage renal disease (creatinine clearance < 60 mL/min)(see section 4.3).

 

Surgery

As Vipdomet contains metformin 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. 

 

Hepatic impairment

Alogliptin has not been studied in patients with severe hepatic impairment (Child-Pugh score >9) and is, therefore, not recommended for use in such patients (see sections 4.2, 4.3 and 5.2).

 

Surgery

As Vipdomet contains metformin, treatment should be discontinued 48 hours before elective surgery with general, spinal or epidural anaesthesia. Treatment should not usually be resumed earlier than 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal.

 

Administration of iodinated contrast agents

The intravascular administration of iodinated contrast agents in radiological studies can lead to renal failure which has been associated with lactic acidosis in patients receiving metformin. Therefore, Vipdomet 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).

 

4.5 Special warnings and precautions for use

Text in red added and text in blue removed:

 

Interactions with metformin

 

Combinations Concomitant use not recommended

 

Alcohol

There is increased risk of lactic acidosis in acute alcohol intoxication (particularly in the case of fasting, malnutrition or hepatic impairment) due to the metformin component (see section 4.4). Consumption of alcohol and medicinal products containing alcohol should be avoided.

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

 

Iodinated contrast agents

Vipdomet 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 4.5.

 

Cationic medicinal products

Cationic substances 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 (400 mg twice daily) increased metformin systemic exposure (area under the curve, 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.

 

Iodinated contrast agents

The intravascular administration of iodinated contrast agents may lead to renal failure resulting in metformin accumulation and a risk of lactic acidosis. Therefore, Vipdomet 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 4.4).

 

Combination requiring precautions for use

 

Some medicinal products can adversely affect renal function which may increase the risk of lactic acidosis, e.g. non‑steroidal anti-inflammatory drugs (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 metformin, close monitoring of renal function is necessary.

 

Medicinal products with intrinsic hyperglycaemic activity

Glucocorticoids (given by systemic and local routes), beta-2-agonists and diuretics (see also section 4.4) have intrinsic hyperglycaemic activity. The patient should be informed and more frequent blood glucose monitoring performed, especially at the beginning of treatment with such medicinal products. If necessary, the dose of Vipdomet should be adjusted during therapy with the other medicinal product and upon its discontinuation.

 

10. Date of revision of the text

Updated text in red:

 

12th December 2016

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 10 - Date of revision of the text

Date of revision of text on the SPC:15-01-2015

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



The following sections have been updated:

4.4 Special warnings and precautions for use: erythema multiforme has been added under hypersensitivity reactions

4.8 Undesirable effects: erythema multiforme has been added to table 2 ‘Spontaneously reported alogliptin post-marketing adverse reactions’. The frequency is listed as unknown.

10 Date of revision of the text: updated to 15 January 2015.

Reasons for adding or updating:

  • Change to section 6.5 - Nature and contents of container
  • Change to section 7 - Marketing authorisation holder
  • Change to section 8 - Marketing authorisation number(s)
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:01-11-2014

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



VIPDOMET

Change to section

 

Details of change

6.5          Nature and contents of container

 

Addition of a pack size (highlighted):

Polychlorotrifluoroethylene (PCTFE)/polyvinyl chloride (PVC) blisters with push through aluminium lidding foil. Pack sizes of 10, 14, 20, 28, 56, 60, 98, 112, 120, 180, 196, 196 (2x98 multipack) or 200 film‑coated tablets.

Not all pack sizes may be marketed.

 

7.            MARKETING AUTHORISATION HOLDER

Takeda Pharma A/S

Dybendal Allé 10

2630 Taastrup

Denmark

8.         MARKETING AUTHORISATION NUMBER(S)

Addition of a MA number (highlighted):

EU/1/13/843/013-024, 026

10. DATE OF REVISION OF THE TEXT

 

Changed to:

1 November 2014

 

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects - how to report a side effect
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:24-07-2014

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

Change to section
Details of change
4.4.  Special warnings and precautions for use
Change in wording
From :
Use with other antihyperglycaemic medicinal products and hypoglycaemia
Vipdomet should not be used in combination with a sulphonylurea, as the safety and efficacy of this combination have not been established.
Insulin is known to cause hypoglycaemia. Therefore, a lower dose of insulin may be considered to reduce the risk of hypoglycaemia when this medicinal product is used in combination with Vipdomet (see section 4.2).
Due to the increased risk of hypoglycaemia in combination with pioglitazone, a lower dose of pioglitazone may be considered to reduce the risk of hypoglycaemia when this drug is used in combination with Vipdomet (see section 4.2).
To:
Use with other antihyperglycaemic medicinal products and hypoglycaemia
Insulin is known to cause hypoglycaemia. Therefore, a lower dose of insulin may be considered to reduce the risk of hypoglycaemia when this medicinal product is used in combination with Vipdomet (see section 4.2).
Due to the increased risk of hypoglycaemia in combination with pioglitazone, a lower dose of pioglitazone may be considered to reduce the risk of hypoglycaemia when this drug is used in combination with Vipdomet (see section 4.2).
Combinations not studied
Vipdomet should not be used in combination with a sulphonylurea, as the safety and efficacy of this combination have not been fully established.
From:
Acute pancreatitis
Use of DPP-4 inhibitors has been associated with a risk of developing acute pancreatitis. In a pooled analysis of the data from 13 studies, the overall rates of pancreatitis reports in patients treated with 25 mg alogliptin, 12.5 mg alogliptin, active control or placebo were 3, 1, 1 or 0 events per 1,000 patient years, respectively. .
To:
Acute pancreatitis
Use of DPP-4 inhibitors has been associated with a risk of developing acute pancreatitis. In a pooled analysis of the data from 13 studies, the overall rates of pancreatitis reports in patients treated with 25 mg alogliptin, 12.5 mg alogliptin, active control or placebo were 2, 1, 1 or 0 events per 1,000 patient years, respectively. In the cardiovascular outcomes study the rates of pancreatitis reports in patients treated with alogliptin or placebo were 3 or 2 events per 1,000 patient years, respectively.
4.8. Undesirable effects
Section 4.8 has been updated with side effects from a cardiovascular outcomes study and pooled safety analysis including a 2-year study
5.1. Pharmacodynamic properties
Section 5. 1 has been updated with the details from a cardiovascular outcomes study and 104-week data from an add-on to metformin study (Table 6)
10. DATE OF REVISION OF THE TEXT
Changed to:
24 July 2014

Reasons for adding or updating:

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

Date of revision of text on the SPC:25-04-2014

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

In Section 4.4, removal of the word 'potential' from the acute pancreatitis warning


Acute pancreatitis

 

Use of DPP‑4 inhibitors has been associated with a potential risk of developing acute pancreatitis.

Reasons for adding or updating:

  • New SPC for new product

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

Legal Category:POM

Black Triangle (CHM): YES