xin: Sitagliptin had a small effect on plasma digoxin concentrations. Following administration of 0.25 mg digoxin concomitantly with 100 mg of sitagliptin daily for 10 days, the plasma AUC of digoxin was increased on average by 11 %, and the plasma Cmax on average by 18 %. No dose adjustment of digoxin is recommended. However, patients at risk of digoxin toxicity should be monitored for this when sitagliptin and digoxin are administered concomitantly.
4.6 Pregnancy and lactation
There are no adequate data from the use of sitagliptin in pregnant women. Studies in animals have shown reproductive toxicity at high doses of sitagliptin (see section 5.3).
A limited amount of data suggest the use of metformin in pregnant women is not associated with an increased risk of congenital malformations. Animal studies with metformin do not indicate harmful effects with respect to pregnancy, embryonic or foetal development, parturition or postnatal development (see also section 5.3).
Janumet should not be used during pregnancy. If a patient wishes to become pregnant or if a pregnancy occurs, treatment with Janumet should be discontinued and switched to insulin treatment as soon as possible.
No studies in lactating animals have been conducted with the combined active substances of Janumet. In studies performed with the individual active substances, both sitagliptin and metformin are excreted in the milk of lactating rats. Metformin is excreted in human milk in small amounts. It is not known whether sitagliptin is excreted in human milk. Janumet must therefore not be used in women who are breast-feeding (see section 4.3).
4.7 Effects on ability to drive and use machines
Janumet has no known influence on the ability to drive and use machines. However, when driving or operating machines, it should be taken into account that dizziness and somnolence have been reported with sitagliptin.
In addition, patients should be alerted to the risk of hypoglycaemia when Janumet is used in combination with sulphonylurea agents or with insulin.
4.8 Undesirable effects
There have been no therapeutic clinical trials conducted with Janumet tablets however bioequivalence of Janumet with co-administered sitagliptin and metformin has been demonstrated (see section 5.2).
Sitagliptin and metformin
Adverse reactions considered as drug related reported in excess (> 0.2 % and difference > 1 patient) of placebo and in patients receiving sitagliptin in combination with metformin in double-blind studies are listed below as MedDRA preferred term by system organ class and absolute frequency (Table 1). 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).
Table 1. The frequency of adverse reactions identified from placebo-controlled clinical studies and post marketing experience
Adverse reaction
Frequency of adverse reaction by treatment regimen
Sitagliptin with Metformin
Sitagliptin with Metformin and a Sulphonylurea
Sitagliptin with Metformin and a PPARγ Agent (rosiglitazone)
Sitagliptin with Metformin and Insulin
Time-point
24-week
24-week
18-week
24-week
Infections a
