1. Name of the medicinal product
Vipdomet 12.5 mg/1000 mg film-coated tablets
2. Qualitative and quantitative composition
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
Film-coated tablet (tablet).
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. Clinical particulars
4.1 Therapeutic indications
Vipdomet is indicated in the treatment of adult patients aged 18 years and older with type 2 diabetes mellitus:
• as an adjunct to diet and exercise to improve glycaemic control in adult patients, inadequately controlled on their maximal tolerated dose of metformin alone, or those already being treated with the combination of alogliptin and metformin.
• in combination with pioglitazone (i.e. triple combination therapy) as an adjunct to diet and exercise in adult patients inadequately controlled on their maximal tolerated dose of metformin and pioglitazone.
• in combination with insulin (i.e. triple combination therapy) as an adjunct to diet and exercise to improve glycaemic control in patients when insulin at a stable dose and metformin alone do not provide adequate glycaemic control.
4.2 Posology and method of administration
Posology
For the different dose regimens Vipdomet is available in strengths of 12.5 mg/850 mg and 12.5 mg/1000 mg film-coated tablets
Adults (≥ 18 years old)
The dose of Vipdomet should be individualised on the basis of the patient's current treatment regimen.
For patients inadequately controlled on the maximal tolerated dose of metformin hydrochloride alone, the recommended dose is one tablet of 12.5 mg/850 mg or 12.5 mg/1,000 mg twice daily, corresponding to 25 mg alogliptin plus 1,700 mg or 2,000 mg metformin hydrochloride daily, depending on the dose of metformin hydrochloride already being taken.
For patients inadequately controlled on dual therapy with a maximal tolerated dose of metformin and pioglitazone, the dose of pioglitazone should be maintained, and Vipdomet administered concomitantly; alogliptin should be dosed at 12.5 mg twice daily (25 mg total daily dose) and metformin hydrochloride at a similar dose (either 850 mg or 1000 mg twice daily) to that already being taken.
Caution should be exercised when alogliptin is used in combination with metformin and a thiazolidinedione as an increased risk of hypoglycaemia has been observed with this triple therapy (see section 4.4). In case of hypoglycaemia, a lower dose of the thiazolidinedione or metformin may be considered.
For patients switching from separate tablets of alogliptin and metformin (as dual therapy or as part of triple therapy with insulin), both alogliptin and metformin should be dosed at the total daily dose already being taken; the individual dose of alogliptin should be halved as it will be taken twice daily whilst the dosing of metformin should remain unchanged.
For patients inadequately controlled on dual combination therapy with insulin and the maximal tolerated dose of metformin, the dose of Vipdomet should provide alogliptin dosed at 12.5 mg twice daily (25 mg total daily dose) and a dose of metformin similar to the dose already being taken.
A lower dose of insulin may be considered to reduce the risk of hypoglycaemia.
The maximum recommended daily dose of 25 mg alogliptin should not be exceeded.
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).
Hepatic impairment
Vipdomet should not be used in patients with hepatic impairment (see sections 4.3 and 5.2).
Paediatric population
The safety and efficacy of Vipdomet in children and adolescents < 18 years old have not been established. No data are available.
Method of administration
Oral use.
Vipdomet should be taken twice daily because of the pharmacokinetics of its metformin component. It should also be taken with meals to reduce the gastrointestinal adverse reactions associated with metformin. The tablets should be swallowed whole with water.
If a dose is missed, it should be taken as soon as the patient remembers. A double dose should not be taken at the same time. In that case, the missed dose should be skipped.
4.3 Contraindications
• 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)
• Diabetic ketoacidosis, diabetic pre-coma
• Moderate and severe renal impairment and end-stage renal disease (creatinine clearance < 60 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
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 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 othe