frequently asked questions about INVOKAMET® XR and INVOKAMET® (canagliflozin/metformin HCl)

Efficacy

While there have been no clinical efficacy studies conducted with INVOKAMET® XR or INVOKAMET®, bioequivalence of INVOKAMET® XR to canagliflozin and metformin XR and of INVOKAMET® to canagliflozin and metformin coadministered as individual tablets has been demonstrated in healthy subjects.1,2

Canagliflozin + metformin XR was studied in a 26-week, double-blind, active-controlled study to evaluate the efficacy and safety of its use as initial therapy.1

INVOKANA® (canagliflozin) has been studied in more than 20,000 patients with type 2 diabetes across 14 completed and 1 ongoing double-blind clinical trials.3

Multiple trials included patients who received INVOKANA® in combination with metformin, with or without other antihyperglycemic agents (AHAs).2,4,5

Placebo-controlled trials included:

  • Metformin
  • Metformin + a sulfonylurea
  • Metformin + pioglitazone
  • Insulin (with or without other AHAs, including metformin)

Active-controlled trials included:

  • 2 trials vs Januvia® (sitagliptin) (1 in combination with metformin* and 1 in combination with metformin + a sulfonylurea)
  • 1 trial vs glimepiride (in combination with metformin)

*Patients were randomized to INVOKANA® 100 mg, INVOKANA® 300 mg, Januvia® 100 mg, or placebo, administered once daily.

References: 1. INVOKAMET® XR [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 2. INVOKAMET® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 3. Data on file. Janssen Pharmaceuticals, Inc., Titusville, NJ. 4. INVOKANA® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 5. Lavalle-González FJ, Januszewicz A, Davidson J, et al. Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial. Diabetologia. 2013;56:2582-2592. Supplemental tables available at: http://link.springer.com/article/10.1007%2Fs00125-013-3039-1 . Accessed October 30, 2018.

Of the 14 completed phase 3 trials with canagliflozin, the study of INVOKAMET® XR vs metformin XR is the only one in which the difference in A1C reductions between the 100-mg and 300-mg doses of canagliflozin was not apparent.1-3

However, a dose-dependent response was observed for those patients achieving A1C <7.0% in the INVOKAMET® XR arms and canagliflozin monotherapy arms, which may be clinically relevant for patients and clinicians.3

References: 1. INVOKANA® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 2. Data on file. Janssen Pharmaceuticals, Inc., Titusville, NJ. 3. Rosenstock J, Chuck L, González-Ortiz M, et al. Initial combination therapy with canagliflozin plus metformin versus each component as monotherapy for drug-naïve type 2 diabetes. Diabetes Care. 2016;39(3):353-362.

Dosage and administration

The choice of prescribing INVOKAMET® XR vs INVOKAMET® is up to you and the individual patient’s needs. Prescribe INVOKAMET® XR if you prefer once-daily dosing for a particular patient. Prescribe INVOKAMET® when you believe twice-daily dosing is appropriate.

The AACE Guidelines recommend use of dual therapy for patients with a baseline A1C ≥7.5%.1

Reference: 1. Garber AJ, Abrahamson MJ, Barzilay JI, et al; American Association of Clinical Endocrinologists, American College of Endocrinology. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm—2018 executive summary. Endocr Pract. 2018;24(1):91-120.

For INVOKAMET® XR, individualize the starting dose based on the patient’s current regimen. Patients should take 2 INVOKAMET® XR tablets once daily with the morning meal. Adjust dosing based on effectiveness and tolerability while not exceeding the maximum recommended daily dose of metformin 2000 mg and canagliflozin 300 mg.1

For INVOKAMET®, individualize the starting dose based on the patient’s current regimen. Patients should take 1 INVOKAMET® tablet twice daily with meals. Adjust dosing based on effectiveness and tolerability while not exceeding the maximum recommended daily dose of metformin 2000 mg and canagliflozin 300 mg.2

References: 1. INVOKAMET® XR [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 2. INVOKAMET® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.

It is recommended that INVOKAMET® XR and INVOKAMET® be taken with meals to reduce the gastrointestinal side effects associated with metformin.1,2

References: 1. INVOKAMET® XR [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 2. INVOKAMET® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.

Safety

All SGLT2 inhibitors are associated with increased urination. INVOKAMET® XR and INVOKAMET® are equivalent to INVOKANA® in terms of SGLT2 effects. In 4 pooled 26-week placebo-controlled trials, including 1 monotherapy trial and 3 add-on combination trials with metformin, the incidence of increased urination, including polyuria, pollakiuria, increased urine output, micturition urgency, and nocturia, was1,2:

  • Placebo (n=646): 0.7%
  • Canagliflozin 100 mg (n=833): 5.1%
  • Canagliflozin 300 mg (n=834): 4.6%

SGLT2=sodium-glucose co-transporter 2.

References: 1. INVOKAMET® XR [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 2. INVOKAMET® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.

Lactic acidosis

Metformin and all metformin-containing products require a boxed warning due to the risk for lactic acidosis caused by metformin accumulation.1,2

Lower-limb amputation

In addition, a 2-fold increased risk of lower-limb amputation with canagliflozin, a component of INVOKAMET® XR and of INVOKAMET®, was observed in CANVAS and CANVAS-R, 2 large, randomized controlled trials in patients with type 2 diabetes who had established cardiovascular disease (CVD) or were at risk for CVD.1,2

In the CANVAS Program, the amputation rate was 0.63 events/100 patient-years in the pooled canagliflozin group and 0.34 events/100 patient-years in the placebo group. In other words, the CANVAS Program showed that treating 100 patients with established CVD or CV risk with canagliflozin for a year led to an additional 0.3 events.3

The risk of amputation was highest in patients with a baseline history of prior amputation, peripheral vascular disease, and neuropathy.1,2

For more information on the risk of amputation, please see the INVOKANA® FAQs or full Prescribing Information, including Boxed WARNINGS, for INVOKAMET® XR and INVOKAMET®.

References: 1. INVOKAMET® XR [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 2. INVOKAMET® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 3. Neal B, Perkovic V, Mahaffey KW, et al; CANVAS Program Collaborative Group. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644-657.