Alogliptin

For patients with moderate renal impairment (CrCl ≥30 to ≤50 mL/min), one-half of the recommended dose of alogliptin should be administered (12.5 mg once daily).

For patients with severe renal impairment (CrCl <30 mL/min) or end-stage renal disease requiring dialysis, one-quarter of the recommended dose of alogliptin should be administered (6.25 mg once daily). Alogliptin may be administered without regard to the timing of dialysis. Experience in patients requiring renal dialysis is limited. Alogliptin has not been studied in patients undergoing peritoneal dialysis.

Experience of alogliptin use in clinical studies in patients with congestive heart failure of New York Heart Association (NYHA) functional class III and IV is limited and caution is warranted in these patients.

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.

Caution should be exercised in patients with a history of pancreatitis.

There are no data from the use of alogliptin in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of alogliptin during pregnancy.

It is unknown whether alogliptin is excreted in human milk. Animal studies have shown excretion of alogliptin in milk. A risk to the suckling child cannot be excluded.

A decision on whether to discontinue breast-feeding or to discontinue alogliptin therapy should be made taking into account the benefit of breast-feeding for the child and the benefit of alogliptin therapy for the woman.

Fertility

The effect of alogliptin on fertility in humans has not been studied. No adverse effects on fertility were observed in animal studies.

Alogliptin has no or negligible influence on the ability to drive and use machines. However patients should be alerted to the risk of hypoglycaemia especially when combined with a sulphonylurea, insulin or combination therapy with thiazolidinedione plus metformin.

Summary of the safety profile

The information provided is based on a total of 9,405 patients with type 2 diabetes mellitus, including 3,750 patients treated with 25 mg alogliptin and 2,476 patients treated with 12.5 mg alogliptin, who participated in one phase 2 or 12 phase 3 double-blind, placebo- or active-controlled clinical studies. In addition, a cardiovascular outcomes study with 5,380 patients with type 2 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 13 studies, the overall incidences of adverse events, serious adverse events and adverse events resulting in discontinuation of therapy were comparable in patients treated with 25 mg alogliptin, 12.5 mg alogliptin, active control or placebo. The most common adverse reaction in patients treated with 25 mg alogliptin was headache.

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

Tabulated list of adverse reactions

The adverse reactions are listed by system organ class and 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 available data).

In the pooled pivotal phase 3 controlled clinical studies of alogliptin as monotherapy and as add-on combination therapy involving 5,659 patients, the observed adverse reactions are listed below.

Adverse reactions:

Paediatric population

In a clinical trial with alogliptin in paediatric patients with type 2 diabetes mellitus aged 10 to 17 years, the profile of adverse reactions was comparable to that observed in adults.