Pharmacy Diabetes

Fixed_Dose-Galvumet

Vildagliptin/metformin hydrochloride

  • GALVUMET film coated tablets are available in 3 strengths:
    - GALVUMET 50/500: 50 mg vildagliptin and 500 mg metformin hydrochloride
    - GALVUMET 50/850: 50 mg vildagliptin and 850 mg metformin hydrochloride
    - GALVUMET 50/1000: 50 mg vildagliptin and 1,000 mg metformin hydrochloride

  • For individuals diagnosed with type 2 diabetes mellitus (T2DM):
    - GALVUMET is indicated as an adjunct to healthy eating and physical activity in individuals whose diabetes is not adequately managed on metformin hydrochloride alone or who are already treated with the combination of vildagliptin and metformin hydrochloride, as separate tablets. Treatment should not be initiated with this fixed-dose combination.
    - GALVUMET is indicated in combination with a sulfonylurea (i.e., triple combination therapy) as an adjunct to healthy eating and physical activity in those inadequately managed with metformin and a sulfonylurea.
    - GALVUMET is indicated as add-on to insulin as an adjunct to healthy eating and physical activity to improve glycaemic management in individuals when stable dose of insulin and metformin alone do not provide adequate glycaemic management.

For the latest PBS indications for GALVUMET please see
https://www.pbs.gov.au/pbs/search?term=galvumet

Life threatening lactic acidosis can occur due to the accumulation of metformin. The main risk factor is renal impairment, other risk factors include old age associated with reduced renal function and high doses of metformin above 2mg per day.

To minimise the risk of lactic acidosis, only one strength of GALVUMET should be prescribed and used at any one time. Individuals should also be advised to discard their previous metformin medication when initiated on GALVUMET.<

  • Initiation of Treatment Adults: The use of diabetes therapy in the management of T2D should be individualized based on effectiveness and tolerability. The recommended starting dose of GALVUMET should be based on the person’ s current regimen of vildagliptin and/or metformin hydrochloride. GALVUMET should be given with meals to reduce the gastrointestinal side effects associated with metformin hydrochloride. When using GALVUMET the maximum daily dose of vildagliptin (100 mg) should not be exceeded. Starting dose for individuals inadequately managed on metformin hydrochloride monotherapy: - Based on the person’s current dose of metformin hydrochloride, GALVUMET may be initiated at either the 50 mg/500 mg, 50 mg/850 mg or 50 mg/1,000 mg tablet strength twice daily. Starting dose for those switching from combination therapy of vildagliptin plus metformin hydrochloride as separate tablets: - GALVUMET may be initiated with either the 50 mg/500 mg, 50 mg/850 mg or 50 mg/1,000 mg tablet strength based on the dose of vildagliptin or metformin already being taken. Use in combination with a sulfonylurea or with insulin: - The dose of GALVUMET should provide vildagliptin dosed as 50 mg twice daily (100 mg total daily dose) and a dose of metformin similar to the dose already being taken. Note: Diabetes MedsCheck with referral to healthcare team for education on hypoglycaemia and blood glucose monitoring.
  • Renal impairment - A GFR should be assessed before initiation of treatment with metformin-containing products (such as GALVUMET) and at least annually thereafter. In individuals at increased risk of further progression of renal impairment and in the elderly, renal function should be assessed more frequently, e.g. every 3 to 6 months. The maximum daily dose of metformin should preferably be divided into 2 to 3 daily doses. Factors that may increase the risk of lactic acidosis should be reviewed before considering initiation of metformin-containing products (such as GALVUMET) in individuals with GFR<60 ml/min. GALVUMET is contraindicated in those with GFR <30 ml/min because of its metformin component. normal and in elderly subjects.
    Note: Diabetes MedsCheck with referral to appropriate healthcare team for annual cycle of care. The following dosing recommendations apply to metformin and vildagliptin, used separately or in combination, in individuals with renal impairment. If no adequate strength of GALVUMET is available, individual components should be used instead of the fixed dose combination.

GALVUMET treatment should not be initiated in individuals ≥ 80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced.

  • GALVUMET is contraindicated in anyone with known hypersensitivity to vildagliptin or metformin hydrochloride or to any of the excipients.
  • GALVUMET is contraindicated in those with severe renal impairment (GFR < 30 ml/min).
  • Congestive Heart Failure GALVUMET is contraindicated in those with congestive heart failure requiring
  • pharmacologic treatment.
  • Metabolic acidosis GALVUMET is contraindicated in individuals with acute or chronic metabolic acidosis, including lactic acidosis or diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin.
  • Radiologic Studies. GALVUMET should be temporarily discontinued in those undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function. Diabetes Medscheck education on side effect profile

  • GALVUMET is not a substitute for insulin in those requiring insulin. GALVUMET should not be used in individuals with T1D or for the treatment of diabetic ketoacidosis.
  • Metformin (Lactic acidosis) Lactic acidosis is a rare, but serious metabolic complication that can occur due to metformin accumulation during treatment with metformin. When it occurs, it is fatal in approximately 50% of cases. Lactic acidosis is a medical emergency and must be treated in hospital immediately. The risk of lactic acidosis increases with the degree of renal dysfunction. Reported cases of lactic acidosis in individuals on metformin have occurred primarily in those with diabetes with significant renal insufficiency, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications. Special caution should be taken in the elderly due to the decrease of renal function with age.
    Note: Diabetes MedsCheck education on side effect profile
  • Cardiac failure - GALVUMET is contraindicated in those with congestive heart failure requiring pharmacologic treatment, which may potentially interact with metformin hydrochloride.
  • Use in hepatic impairment - Vildagliptin, and hence GALVUMET is not recommended in individuals with clinical or laboratory evidence of hepatic impairment, including those with pre-treatment ALT or AST >2.5x the ULN. Since impaired hepatic function has been associated with some cases of lactic acidosis (a risk associated with metformin hydrochloride), metformin-containing products (such as GALVUMET) should generally be avoided in anyone with clinical or laboratory evidence of hepatic disease.

  • Metformin
    - Gastrointestinal disorders: Gastrointestinal symptoms such as nausea, vomiting, diarrhoea, abdominal pain, and loss of appetite are very common (>10%): these occur most frequently during initiation of therapy and resolve spontaneously in most cases. To prevent these gastrointestinal symptoms, it is recommended that this medicinal product be taken in 2 or 3 daily doses. A slow increase of the dose may also improve gastrointestinal tolerability. Increase risk of Vitamin B12 deficiency. See clinical interventions for more detail.
    - Metabolism and nutrition disorders: Lactic acidosis is a very rare (<0.01%) but serious metabolic complication that can occur due to metformin accumulation during treatment with metformin. The onset of lactic acidosis is often subtle and accompanied only by non-specific symptoms such as malaise, myalgia, respiratory distress, increasing somnolence and non-specific abdominal distress. There may be associated hypothermia, hypotension and resistant bradyarrhythmias with more marked acidosis.
    Note: Diabetes MedsCheck with education on signs and symptoms of lactic acidosis and referral to healthcare team when required.
  • Hepatobiliary disorders: Very rare: liver function test abnormalities or hepatitis requiring treatment discontinuation.
  • Skin and subcutaneous tissue disorders: Skin reactions such as erythema, pruritus and urticaria have been reported but the incidence is very rare (<0.01%).
  • Nervous system disorders - Taste disturbance (3 %) is common.
  • Bullous pemphigoid: Post-marketing cases of bullous pemphigoid requiring hospitalisation have been reported with DPP4 inhibitor use. In reported cases, patients typically recovered with topical or systemic immunosuppressive treatment and discontinuation of the DPP-4 inhibitor. Tell individuals to report development of blisters or erosions while receiving GALVUMET. If bullous pemphigoid is suspected, GALVUMET should be discontinued and referral to a dermatologist should be considered for diagnosis and appropriate treatment
    Note: Diabetes MedsCheck with education on side effect profile and referral to healthcare team when required.
  • Arthralgia: There have been post marketing reports of joint pain, which may be severe, in those taking DPP4 inhibitors. Onset of symptoms following initiation of treatment may be rapid or may occur after longer periods. Discontinuation of therapy should be considered in individuals who present with or experience an exacerbation of joint symptoms during treatment with Vildagliptin.
    Note: Diabetes MedsCheck with education on side effect profile and referral to healthcare team when required.

In the bioequivalence studies of GALVUMET at three dose strengths (50 mg/500 mg, 50 mg/850 mg and 50 mg/1,000 mg), versus free combination of vildagliptin and metformin hydrochloride tablets at the corresponding doses, the area under the curve (AUC) and maximum concentration (Cmax) of both the vildagliptin component and the metformin hydrochloride component of the GALVUMET tablets were demonstrated to be bioequivalent to that of free combination tablets. Food does not affect the extent and rate of absorption of vildagliptin from GALVUMET.

- Vildagliptin - Vildagliptin is rapidly absorbed with an absolute oral bioavailability of 85%. Peak plasma concentrations for vildagliptin and the area under the plasma concentration versus time curve increased in an approximately dose-proportional manner over the therapeutic dose range. Following oral administration in the fasting state, vildagliptin is rapidly absorbed with peak plasma concentrations observed at 1.75 hours. Co-administration with food slightly decreases the rate of absorption of vildagliptin, as characterized by a 19% decrease in peak concentrations, and a delay in the time to peak plasma concentration to 2.5 hours. There is no change in the extent of absorption, and food does not alter the overall exposure (AUC).

- Metformin Hydrochloride - Studies using single oral doses of metformin tablets indicate a lack of dose proportionality, due to increased absorption of metformin with increasing doses. The absolute bioavailability of a 500 mg metformin hydrochloride tablet given under fasting conditions is approximate 50 to 60%.

  • Vildagliptin: The plasma-protein binding of vildagliptin is low (9.3%), and vildagliptin distributes equally between plasma and red blood cells. The mean volume of distribution of vildagliptin at steady state after intravenous administration (Vss) is 71 litres, suggesting extravascular distribution.
  • Metformin Hydrochloride: The apparent volume of distribution (V/F) of metformin hydrochloride following single oral doses of 850 mg averaged 654 ± 358 litres. Metformin hydrochloride is negligibly bound to plasma proteins, in contrast to sulfonylureas, which are more than 90% protein bound.

  • Vildagliptin: Metabolism is the major elimination pathway for vildagliptin in humans, accounting for 69% of the dose. The major metabolite, LAY151, is pharmacologically inactive.
  • Metformin Hydrochloride: Metformin is excreted unchanged in the urine and does not undergo hepatic metabolism. In patients with significantly decreased renal function, the plasma half-life of metformin is prolonged and renal clearance is decreased.

  • Vildagliptin: Following oral administration of [14C]-vildagliptin, approximately 85% of the dose is excreted into the urine and 15% of the dose is recovered in the faeces. Renal excretion of the unchanged vildagliptin accounts for 23% of the dose after oral administration. After an intravenous administration to healthy subjects, the total plasma and renal clearances of vildagliptin are 41 litres/hour and 13 litres/hour, respectively. The mean elimination half-life after intravenous administration is approximately 2 hours. The elimination half-life after oral administration is approximately 3 hours and is independent of the dose.
    - Metformin Hydrochloride: Intravenous single-dose studies in normal subjects demonstrate that metformin hydrochloride is excreted unchanged in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) or biliary excretion. Renal clearance is approximately 3.5 times greater than creatinine clearance, which indicates that tubular secretion is the major route of elimination. Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, with a plasma elimination half-life of approximately 6.2 hours. In blood, the elimination half-life is approximately 17.6 hours, suggesting that the erythrocyte mass may be a compartment of distribution.

For more detailed information on this product please consult the product information.

https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-02841-3&d=202106121016933