Galvus Met Adverse Reactions

Galvus Met: The data presented here relate to co-administration of vildagliptin and metformin as a free or fixed-dose combination.
Rare cases of angioedema have been reported with vildagliptin at a rate similar to that in the control group. A greater number 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.
Rare cases of hepatic dysfunction (including hepatitis) have been reported with vildagliptin. In these cases, the patients were generally asymptomatic, without clinical sequelae, and hepatic function returned to normal after discontinuation of treatment. In controlled monotherapy and add-on therapy studies of up to 24 weeks' duration, the incidence of ALT or AST elevations ≥3 x ULN (detected at no fewer than two consecutive measurements or at the final on-treatment visit) was 0.2% for 50 mg vildagliptin once daily, 0.3% for 50 mg vildagliptin twice daily and 0.2% for all comparators. These increases in transaminases were generally asymptomatic, not progressive and not associated with cholestasis or jaundice.
In controlled studies, hypoglycaemia was uncommon in patients receiving vildagliptin in combination with metformin and in patients receiving placebo and metformin. No severe cases of hypoglycaemia occurred in the vildagliptin group.
Gastrointestinal adverse effects, including diarrhoea and nausea, occur very commonly during the introduction of metformin.
Overall, gastrointestinal symptoms were reported in 12.9% of patients treated with the combination of vildagliptin and metformin, compared with 18.1% of patients treated with metformin alone.
In comparative controlled monotherapy studies, hypoglycaemia was uncommon.
Adverse effects reported in patients who received vildagliptin in double-blind studies as monotherapy and add-on therapy are listed below by system organ class and absolute frequency. Frequencies are defined as: Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10 000 to <1/1000), very rare (<1/10 000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse effects are ranked in order of decreasing seriousness.
Infections and infestations: Very rare: Upper respiratory tract infections, nasopharyngitis.
Endocrine disorders: Not known: Pancreatitis.
Nervous system disorders: Common: Dizziness, tremor.
Uncommon: Headache.
Vascular disorders: Uncommon: Peripheral oedema.
Gastrointestinal disorders: Common: Nausea.
Uncommon: Diarrhoea, constipation.
Hepatic disorders: Rare: Elevated transaminase levels.
Musculoskeletal disorders: Uncommon: Arthralgia.
Metabolism disorders: Uncommon: Hypoglycaemia, weight gain.
General disorders: Uncommon: Asthenia.
None of the adverse effects reported with vildagliptin monotherapy were observed at clinically significantly higher rates when vildagliptin was administered concomitantly with metformin.
Post-marketing experience: The following additional adverse drug reaction has been reported during the post-marketing period: Rare cases of hepatitis that resolved following discontinuation of Galvus Met (see Precautions).
Frequency not known: Urticaria, pancreatitis, bullous and exfoliative skin lesions (including bullous pemphigoid), localized exfoliation and blistering of the skin.
Metformin: The known adverse effects of metformin are summarized as follows.
Blood and lymphatic system disorders: Isolated cases of leukopenia, thrombocytopenia and haemolytic anaemia.
Very rare: Reduced vitamin B₁₂ blood levels.
Metabolism and nutrition disorders: Very rare: Lactic acidosis (incidence: 3 cases per 100 000 patient-years; see Precautions).
Nervous system disorders: Common: Metallic taste (3%).
Uncommon: Fatigue.
Gastrointestinal disorders: Common to very common: Gastrointestinal disorders (5-15%) such as nausea, vomiting, diarrhoea, abdominal pain and loss of appetite.
These symptoms usually occur at the start of treatment and resolve spontaneously in most cases.
Hepatobiliary disorders: Isolated cases: Abnormal results in hepatic function tests, e.g. elevated transaminases or hepatitis (reversible after discontinuing metformin).
Skin and subcutaneous tissue disorders: Very rare: Skin reactions such as erythema, pruritus, urticaria.
Combination of vildagliptin with insulin (with/without metformin): The incidence of hypoglycaemia in the controlled clinical studies conducted was similar in both treatment groups (14.0% of patients on vildagliptin vs. 16.4% of patients on placebo). Severe hypoglycaemia occurred in n = 2 patients on vildagliptin vs. n = 6 on placebo. The overall effect on mean weight was small in both treatment groups (+0.6 kg on vildagliptin vs. ±0 kg on placebo).
The following adverse effects occurred with vildagliptin in these studies: Metabolism and nutrition disorders: Common: Decreased blood glucose.
Nervous system disorders: Common: Headache, chills.
Gastrointestinal disorders: Common: Nausea, gastro-oesophageal reflux disease.
Uncommon: Diarrhoea, flatulence.
Discontinuations due to these adverse effects were rare overall.
Combination with a sulphonylurea: Hypoglycaemia was common in both treatment groups (5.1% for vildagliptin + metformin + glimepiride vs. 1.9 % for placebo + metformin + glimepiride). One severe hypoglycaemic event was reported in the vildagliptin group. At the end of the study, the effect on mean body weight was small (+0.6 kg in the vildagliptin group and 0.1 kg in the placebo group).
Adverse effects in patients who received Galvus 50 mg twice daily in combination with metformin and a sulphonylurea (n = 157): Metabolism and nutrition disorders: Common: Hypoglycaemia.
Nervous system disorders: Common: Dizziness, tremor.
Skin disorders: Common: Hyperhidrosis.
General disorders: Common: Asthenia.