01 Oct 2012

Galvus 50 (Vildagliptin) - United Kingdom

Updated: 01 Oct 2012

Galvus 50 mg Tablets

Vildagliptin is indicated in the treatment of type 2 diabetes mellitus in adults:

As monotherapy

- in patients inadequately controlled by diet and exercise alone and for whom metformin is inappropriate due to contraindications or intolerance.

As dual oral therapy in combination with

- metformin, in patients with insufficient glycaemic control despite maximal tolerated dose of monotherapy with metformin,

- a sulphonylurea, in patients with insufficient glycaemic control despite maximal tolerated dose of a sulphonylurea and for whom metformin is inappropriate due to contraindications or intolerance,

- a thiazolidinedione, in patients with insufficient glycaemic control and for whom the use of a thiazolidinedione is appropriate.

Galvus 50 Description, Presentation and Dosage

Galvus 50 Description

Galvus 50 Drug Class Description

Drugs used in diabetes, dipeptidyl peptidase 4 (DPP-4) inhibitors - ATC code: A10BH02

Galvus 50 Drug Description

Each tablet contains 50mg of vildagliptin.

Excipient with known effect: Each tablet contains 47.82 mg anhydrous lactose.

Galvus 50 Generic Name

Vildagliptin

Galvus 50 Presentation

Galvus 50 Presentation

Tablet.

White to light yellowish, round (8mm diameter), flat-faced, bevelled-edge tablet. One side is debossed with “NVR”, and the other side with “FB”.

Free Medical Education Resources

Galvus 50 Dosage

Galvus 50 Adult Dosage

Posology

Adults

When used as monotherapy or in dual combination with metformin or a thiazolidinedione, the recommended daily dose of vildagliptin is 100mg, 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 50mg once daily administered in the morning. In this patient population, vildagliptin 100mg daily was no more effective than vildagliptin 50mg once daily.

Doses higher than 100mg are not recommended.

If a dose of Galvus is missed, it should be taken as soon as the patient remembers. A double dose should not be taken on the same day.

The safety and efficacy of vildagliptin as triple oral therapy in combination with metformin and a thiazolidinedione or with metformin and a sulphonylurea has not been established.

Additional information on special populations

Elderly (≥ 65 years)

No dose adjustments are necessary in elderly patients.

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 with end-stage renal disease (ESRD), the recommended dose of Galvus is 50 mg once daily.

Hepatic impairment

Galvus 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).

Paediatric population

Galvus is not recommended for use in children and adolescents under 18 years due to a lack of data on safety and efficacy.

Method of administration

Oral use

Galvus can be administered with or without a meal.

Galvus 50 Precautions, Reactions and Contraindications

Galvus 50 Special Precautions

Galvus 50 Special Precautions

General

Galvus is not a substitute for insulin in insulin-requiring patients. Galvus 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 Galvus should be used with caution in these patients.

Hepatic impairment

Galvus 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 Galvus in order to know the patient's baseline value. Liver function should be monitored during treatment with Galvus 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 Galvus 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 normalisation, treatment with Galvus should not be reinitiated.

Cardiac failure

There is no experience of vildagliptin use in clinical trials in patients with NYHA functional class III-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.

Resolution of pancreatitis has been observed after discontinuation of vildagliptin. If pancreatitis is suspected, vildagliptin and other potentially suspect medicinal products should be discontinued.

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.

Galvus 50 Adverse Reactions

Galvus 50 Adverse Reactions

Summary of the safety profile

Safety data were obtained from a total of 3,784 patients exposed to vildagliptin at a daily dose of 50mg (once daily) or 100mg (50mg twice daily or 100mg once daily) in controlled trials of at least 12 weeks duration. Of these patients, 2,264 patients received vildagliptin as monotherapy and 1,520 patients received vildagliptin in combination with another medicinal product. 2,682 patients were treated with vildagliptin 100mg daily (either 50mg twice daily or 100mg once daily) and 1,102 patients were treated with vildagliptin 50mg once daily.

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.

Rare cases of hepatic dysfunction (including hepatitis) have been reported. 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.

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 angiotensin converting enzyme inhibitor (ACE-Inhibitor). The majority of events were mild in severity and resolved with ongoing vildagliptin treatment.

Tabulated list of adverse reactions

Adverse reactions reported in patients who received Galvus in double-blind studies as monotherapy and add-on therapies are listed below for each indication 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.

Combination with metformin

Table 1 Adverse reactions reported in patients who received Galvus 100mg daily in combination with metformin in double-blind studies (N=208)

Metabolism and nutrition disorders

Common

Hypoglycaemia

Nervous system disorders

Common

Tremor

Common

Headache

Common

Dizziness

Uncommon

Fatigue

Gastrointestinal disorders

Common

Nausea

Description of selected adverse reactions

In controlled clinical trials with the combination of vildagliptin 100 mg daily + metformin, no withdrawal due to adverse reactions was reported in either the vildagliptin 100 mg daily + metformin or the placebo + metformin treatment groups.

In clinical trials, the incidence of hypoglycaemia was common in patients receiving vildagliptin 100 mg daily in combination with metformin (1%) and uncommon in patients receiving placebo + metformin (0.4%). No severe hypoglycaemic events were reported in the vildagliptin arms.

In clinical trials, weight did not change from baseline when vildagliptin 100 mg daily was added to metformin (+0.2 kg and -1.0 kg for vildagliptin and placebo, respectively).

Clinical trials of up to more than 2 years' duration did not show any additional safety signals or unforeseen risks when vildagliptin was added on to metformin.

Combination with a sulphonylurea

Table 2 Adverse reactions reported in patients who received Galvus 50mg in combination with a sulphonylurea in double-blind studies (N=170)

Infections and infestations

Very rare

Nasopharyngitis

Metabolism and nutrition disorders

Common

Hypoglycaemia

Nervous system disorders

Common

Tremor

Common

Headache

Common

Dizziness

Common

Asthenia

Gastrointestinal disorders

Uncommon

Constipation

Description of selected adverse reactions

In controlled clinical trials with the combination of vildagliptin 50 mg + a sulphonylurea, the overall incidence of withdrawals due to adverse reactions was 0.6% in the vildagliptin 50 mg + sulphonylurea vs 0% in the placebo + sulphonylurea treatment group.

In clinical trials, the incidence of hypoglycaemia when vildagliptin 50 mg once daily was added to glimepiride was 1.2% versus 0.6% for placebo + glimepiride. No severe hypoglycaemic events were reported in the vildagliptin arms.

In clinical trials, weight did not change from baseline when vildagliptin 50 mg daily was added to glimepiride (-0.1 kg and -0.4 kg for vildagliptin and placebo, respectively).

Combination with a thiazolidinedione

Table 3 Adverse reactions reported in patients who received Galvus 100mg daily in combination with a thiazolidinedione in double-blind studies (N=158)

Metabolism and nutrition disorders

Common

Weight increase

Uncommon

Hypoglycaemia

Nervous system disorders

Uncommon

Headache

Uncommon

Asthenia

Vascular disorders

Common

Oedema peripheral

Description of selected adverse reactions

In controlled clinical trials with the combination of vildagliptin 100 mg daily+ a thiazolidinedione, no withdrawal due to adverse reactions was reported in either the vildagliptin 100 mg daily + thiazolidinedione or the placebo + thiazolidinedione treatment groups.

In clinical trials, the incidence of hypoglycaemia was uncommon in patients receiving vildagliptin + pioglitazone (0.6%) but common in patients receiving placebo + pioglitazone (1.9%). No severe hypoglycaemic events were reported in the vildagliptin arms.

In the pioglitazone add-on study, the absolute weight increases with placebo, Galvus 100 mg daily were 1.4 and 2.7 kg, respectively.

The incidence of peripheral oedema when vildagliptin 100 mg daily was added to a maximum dose of background pioglitazone (45 mg once daily) was 7.0%, compared to 2.5% for background pioglitazone alone.

Monotherapy

Table 4 Adverse reactions reported in patients who received Galvus 100 mg daily as monotherapy in double-blind studies (N=1,855)

Infections and infestations

Very rare

Upper respiratory tract infection

Very rare

Nasopharyngitis

Metabolism and nutrition disorders

Uncommon

Hypoglycaemia

Nervous system disorders

Common

Dizziness

Uncommon

Headache

Vascular disorders

Uncommon

Oedema peripheral

Gastrointestinal disorders

Uncommon

Constipation

Musculoskeletal and connective tissue disorders

Uncommon

Arthralgia

Description of selected adverse reactions

In addition, in controlled monotherapy trials with vildagliptin the overall incidence of withdrawals due to adverse reactions was no greater for patients treated with vildagliptin at doses of 100 mg daily (0.3%) than for placebo (0.6%) or comparators (0.5%).

In comparative controlled monotherapy studies, hypoglycaemia was uncommon, reported in 0.4% (7 of 1,855) of patients treated with vildagliptin 100 mg daily compared to 0.2% (2 of 1,082) of patients in the groups treated with an active comparator or placebo, with no serious or severe events reported.

In clinical trials, weight did not change from baseline when vildagliptin 100 mg daily was administered as monotherapy (-0.3 kg and -1.3 kg for vildagliptin and placebo, respectively).

Clinical trials of up to 2 years' duration did not show any additional safety signals or unforeseen risks with vildagliptin monotherapy.

Post-marketing experience

Table 5 Post-marketing adverse reactions

Gastrointestinal disorders

Not known

Pancreatitis

Hepatobiliary disorders

Not known

Hepatitis (reversible upon discontinuation of the medicinal product)

Abnormal liver function tests (reversible upon discontinuation of the medicinal product)

Skin and subcutaneous tissue disorders

Not known

Urticaria

Bullous or exfoliative skin lesions

Galvus 50 Contraindications

Galvus 50 Contraindications

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

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