Lactation

It is unknown whether sitagliptin is excreted in human breast milk. Animal studies have shown excretion of sitagliptin in breast milk. Januvia should not be used during breast-feeding.

4.7 Effects on ability to drive and use machines
Januvia 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.

In addition, patients should be alerted to the risk of hypoglycaemia when Januvia is used in combination with sulphonylurea agents or with insulin.

4.8 Undesirable effects

  In 11 large clinical trials of up to 2 years in duration, over 3,200 patients have received treatment with Januvia 100 mg per day alone or in combination with metformin, a sulphonylurea (with or without metformin), insulin (with or without metformin), or a PPARγ agent (with or without metformin). In a pooled analysis of 9 of these trials, the rate of discontinuation due to adverse experiences considered drug-related was 0.8 % with 100 mg per day and 1.5 % with other treatments. No adverse reactions considered as drug-related were reported in patients treated with sitagliptin occurring in excess (> 0.2 % and difference > 1 patient) of that in patients treated with control. In an additional combination study with a PPARγ agent (rosiglitazone) and metformin, no patients were discontinued due to adverse experiences considered as drug-related.

Adverse reactions considered as drug-related (except where noted), reported in patients treated with sitagliptin occurring in excess (> 0.2 % and difference > 1 patient) of that in patients treated with placebo, are listed below (Table 1) 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); and 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 Monotherapy
 Sitagliptin with Metformin
 Sitagliptin with a Sulphonylurea
 Sitagliptin with a Sulphonylurea and Metformin
 Sitagliptin with a PPAR γ Agent (pioglitazone)
 Sitagliptin with a PPARγ Agent (rosiglitazone) and Metformin
 Sitagliptin with Insulin (+/-) Metformin)
 
Time-point
 24-week
 24-week
 24-week
 24-week
 24-week
 18-week
 24-week
 
            
Infections and infestations
 
influenza
             Common
 
upper respiratory tract infection
 Common†
           
nasopharyngitis
 Common†
           
fungal skin infection
           Uncommon§
 
        &nbs