Galvus 50 mg

/ Novartis

Adults: The management of antidiabetic therapy should be individualized. The recommended dose is 50 mg or 100 mg daily for monotherapy. The 50 mg dose should be administered once daily in the morning. The 100 mg dose should be administered as two divided doses of 50 mg given in the morning and evening. When used in combination with metformin, in combination with thiazolidinedione, in combination with metformin and a SU or in combination with insulin (with or without metformin), the recommended daily dose of vildagliptin is 100 mg, administered as one dose of 50 mg in the morning and one dose of 50 mg in the evening. When used in dual combination with a sulphonylurea, the recommended dose of vildagliptin is 50 mg once daily administered in the morning. In this patient population, vildagliptin 100 mg daily was no more effective than vildagliptin 50 mg once daily. When used in combination with a sulphonylurea, a lower dose of the sulphonylurea may be considered to reduce the risk of hypoglycaemia. Daily doses higher than 100 mg are not recommended. The safety and efficacy of vildagliptin as triple oral therapy in combination with metformin and a thiazolidinedione have not been established.
Additional information on special populations Renal impairment: No dose adjustment is required in patients with mild renal impairment (creatinine clearance ≥ 50 ml/min). In patients with moderate or severe renal impairment or End Stage Renal Disease (ESRD), the recommended dose  is 50 mg once daily.
Hepatic impairment: It should not be used in patients with hepatic impairment, including patients with pre-treatment alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3x the upper limit of normal (ULN).
Elderly (≥ 65 years): No dose adjustments are necessary in elderly patients.
Pediatric population: It is not recommended for use in children and adolescents (< 18 years) due to a lack of data on safety and efficacy.
Method of administration: Oral use: Can be administered with or without a meal.

As an adjunct to diet and exercise in patients with type 2 diabetes mellitus: As monotherapy, if diet and exercise are not sufficient. In combination  with metformin, or a sulfonylurea if treatment with these oral antidiabetics does not offer sufficient control of blood glucose. In combination with a thiazolidinedione, in patients with insufficient glycaemic control and for whom the use of a thiazolidinedione is appropriate. As triple oral therapy in combination with: a sulphonylurea and metformin when diet and exercise plus dual therapy with these agents do not provide adequate glycaemic control.

Hypersensitivity to the active substance or to any of the excipients.

General: It is not a substitute for insulin in insulin-requiring patients. Its should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
Renal impairment: There is limited experience in patients with ESRD on haemodialysis. Therefore it should be used with caution in these patients.
Hepatic impairment: It should not be used in patients with hepatic impairment, including patients with pre-treatment ALT or AST > 3x ULN.
Liver enzyme monitoring: Rare cases of hepatic dysfunction (including hepatitis) have been reported. In these cases, the patients were generally asymptomatic without clinical sequelae and liver function test results returned to normal after discontinuation of treatment. Liver function tests should be performed prior to the initiation of treatment with this drug in order to know the patient’s baseline value. Liver function should be monitored during treatment at three-month intervals during the first year and periodically thereafter. Patients who develop increased transaminase levels should be monitored with a second liver function evaluation to confirm the finding and be followed thereafter with frequent liver function tests until the abnormality(ies) return(s) to normal. Should an increase in AST or ALT of 3x ULN or greater persist, withdrawal of this drug therapy is recommended. Patients who develop jaundice or other signs suggestive of liver dysfunction should discontinue Galvus. Following withdrawal of treatment with Galvus and LFT normalization, treatment with Galvus should not be reinitiated.
Heart Failure: A clinical trial of vildagliptin in patients with NYHA functional class I-III showed that treatment with vildagliptin was not associated with a change in left-ventricular function or worsening of pre-existing CHF versus placebo Clinical experience in patients with NYHA functional class III treated with vildagliptin is still limited and results are inconclusive. There is no experience of vildagliptin use in clinical trials in patients with NYHA functional class IV and therefore use is not recommended in these patients.
Skin disorders: Skin lesions, including blistering and ulceration have been reported in extremities of monkeys in non-clinical toxicology studies. Although skin lesions were not observed at an increased incidence in clinical trials, there was limited experience in patients with diabetic skin complications. Furthermore, there have been post-marketing reports of bullous and exfoliative skin lesions. Therefore, in keeping with routine care of the diabetic patient, monitoring for skin disorders, such as blistering or ulceration, is recommended.
Pancreatitis: In post-marketing experience there have been spontaneously reported adverse reactions of acute pancreatitis. Patients should be informed of the characteristic symptom of acute pancreatitis: persistent, severe abdominal pain (sometimes radiating to the back) and encouraged to tell their healthcare provider if they have such symptoms. In most cases, resolution of pancreatitis has been observed after discontinuation of vildagliptin. If pancreatitis is suspected, vildagliptin and other potentially suspect medicinal products should be discontinued.
Hypoglycaemia: Sulphonylureas are known to cause hypoglycaemia. Patients receiving vildagliptin in combination with a sulphonylurea may be at risk for hypoglycaemia. Therefore, a lower dose of sulphonylurea may be considered to reduce the risk of hypoglycaemia.
Excipients: The tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
For full details see prescribing information.

The majority of adverse reactions in these trials were mild and transient, not requiring treatment discontinuations. No association was found between adverse reactions and age, ethnicity, duration of exposure or daily dose. In combination with metformin: Tremor, headache, dizziness, nausea, hypoglycemia. In combination with a sulphonylurea: Tremor, headache, dizziness, asthenia, hypoglycemia. In combination with a thiazolidinedione: Weight increase, edema peripheral. Monotherapy: Dizziness.
For full details see prescribing information.

Vildagliptin has a low potential for interactions with co-administered medicinal products. Since vildagliptin is not a cytochrome P (CYP) 450 enzyme substrate and does not inhibit or induce CYP 450 enzymes, it is not likely to interact with active substances that are substrates, inhibitors or inducers of these enzymes.
Combination with pioglitazone, metformin and glyburide: Results from studies conducted with these oral antidiabetics have shown no clinically relevant pharmacokinetic interactions.
Digoxin (Pgp substrate), warfarin (CYP2C9 substrate): Clinical studies performed with healthy subjects have shown no clinically relevant pharmacokinetic interactions. However, this has not been established in the target population.
Combination with amlodipine, ramipril, valsartan or simvastatin: Drug-drug interaction studies in healthy subjects were conducted with amlodipine, ramipril, valsartan and simvastatin. In these studies, no clinically relevant pharmacokinetic interactions were observed after co-administration with vildagliptin. As with other oral antidiabetic medicinal products the hypoglycemic effect of vildagliptin may be reduced by certain active substances, including thiazides, corticosteroids, thyroid products and sympathomimetics.
Combination with ACE-inhibitors: There may be an increased risk of angioedema in patients concomitantly taking ACE-inhibitors
As with other oral antidiabetic medicinal products the hypoglycemic effect of vildagliptin may be reduced by certain active substances, including thiazides, corticosteroids, thyroid products and sympathomimetics.

Pregnancy: There are no adequate data from the use of vildagliptin in pregnant women. Studies in animals have shown reproductive toxicity at high doses. The potential risk for humans is unknown. Due to lack of human data, this drug not be used during pregnancy.
Lactation: It is not known whether vildagliptin is excreted in human breast milk. Animal studies have shown excretion of vildagliptin in milk. it should not be used during lactation. No studies on the effect on human fertility have been conducted.

Symptoms: Information regarding overdose with Vildagliptin is limited. Information on the likely symptoms of overdose was taken from a rising dose tolerability study in healthy subjects given Vildagliptin for 10 days. At 400 mg, there were three cases of muscle pain, and individual cases of mild and transient paresthesia, fever, edema and a transient increase in lipase levels. At 600 mg, one subject experienced edema of the feet and hands, and increases in creatine phosphokinase (CPK), aspartate aminotransferase (AST), C-reactive protein (CRP) and myoglobin levels. Three other subjects experienced edema of the feet, with paresthesia in two cases. All symptoms and laboratory abnormalities resolved without treatment after discontinuation of the study medicinal product.
Management: In the event of an overdose, supportive management is recommended. Vildagliptin cannot be removed by hemodialysis. However, the major hydrolysis metabolite (LAY 151) can be removed by hemodialysis.

Before/after meal: Can be administered with or without a meal.
Storage: Store below 30°C. Store in the original package in order to protect from moisture.