Galvus Met Adverse Reactions

Summary of the safety profile: Safety data were obtained from a total of 6 197 patients exposed to vildagliptin/metformin in randomised placebo-controlled trials. Of these patients, 3 698 patients received vildagliptin/metformin and 2 499 patients received placebo/metformin.
There have been no therapeutic clinical trials conducted with Galvus Met. However, bioequivalence of Galvus Met with co-administered vildagliptin and metformin has been demonstrated (see Pharmacology: Pharmacokinetics under Actions).
The majority of adverse reactions were mild and transient, not requiring treatment discontinuations. No association was found between adverse reactions and age, ethnicity, duration of exposure or daily dose. Vildagliptin use is associated with the risk of development of pancreatitis. Lactic acidosis has been reported following the use of metformin, especially in patients with underlying renal impairment (see Precautions).
Tabulated list of adverse reactions: Adverse reactions reported in patients who received vildagliptin in double-blind clinical trials as monotherapy and add-on therapies are listed as follows by system organ class and absolute 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 the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. (See Table 2.)

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Description of selected adverse reactions: Vildagliptin: Hepatic impairment: Rare cases of hepatic dysfunction (including hepatitis) have been reported with vildagliptin. In these cases, the patients were generally asymptomatic without clinical sequelae and liver function returned to normal after discontinuation of treatment. In data from controlled monotherapy and add-on therapy trials of up to 24 weeks in duration, the incidence of ALT or AST elevations ≥3x ULN (classified as present on at least 2 consecutive measurements or at the final on-treatment visit) was 0.2%, 0.3% and 0.2% for vildagliptin 50 mg once daily, vildagliptin 50 mg twice daily and all comparators, respectively. These elevations in transaminases were generally asymptomatic, non-progressive in nature and not associated with cholestasis or jaundice.
Angioedema: Rare cases of angioedema have been reported on vildagliptin at a similar rate to controls. A greater proportion of cases were reported when vildagliptin was administered in combination with an ACE inhibitor. The majority of events were mild in severity and resolved with ongoing vildagliptin treatment.
Hypoglycaemia: Hypoglycaemia was uncommon when vildagliptin (0.4%) was used as monotherapy in comparative controlled monotherapy studies with an active comparator or placebo (0.2%). No severe or serious events of hypoglycaemia were reported. When used as an add-on to metformin, hypoglycaemia occurred in 1% of vildagliptin-treated patients and in 0.4% of placebo-treated patients. When pioglitazone was added, hypoglycaemia occurred in 0.6% of vildagliptin-treated patients and in 1.9% of placebo-treated patients. When sulphonylurea was added, hypoglycaemia occurred in 1.2% of vildagliptin-treated patients and in 0.6% of placebo-treated patients. When sulphonylurea and metformin were added, hypoglycaemia occurred in 5.1% of vildagliptin-treated patients and in 1.9% of placebo-treated patients. In patients taking vildagliptin in combination with insulin, the incidence of hypoglycaemia was 14% for vildagliptin and 16% for placebo.
Metformin: Decrease of vitamin B12 absorption: A decrease in vitamin B12 absorption with decrease in serum levels has been observed very rarely in patients who have been treated with metformin over a long period. Consideration of such aetiology is recommended if a patient presents with megaloblastic anaemia.
Liver function: Isolated cases of liver function test abnormalities or hepatitis resolving upon metformin discontinuation have been reported.
Gastrointestinal disorders: Gastrointestinal adverse reactions occur most frequently during initiation of therapy and resolve spontaneously in most cases. To prevent them, it is recommended that metformin be taken in 2 daily doses during or after meals. A slow increase in the dose may also improve gastrointestinal tolerability.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.