frequently asked questions about INVOKANA®

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Genital mycotic infection (GMI)

GMI occurred more frequently in female patients than in male patients.1

In 4 pooled 26-week placebo-controlled trials1:

  • Male patients with a history of GMI and uncircumcised men were more likely to experience infection
  • Female patients with a history of GMI were more likely to experience infection

Reference: 1. INVOKANA® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.

Males: In general, good hygiene is always recommended, and cleaning beneath the foreskin with soap and water is advised in uncircumcised patients.1

Females: Inform female patients of the potential for GMI and provide them with information on the signs and symptoms. In general, women can reduce their risk of developing GMI by2:

  • Avoiding douches
  • Avoiding scented hygiene products
  • Changing tampons and pads often during menstruation
  • Avoiding tight underwear or clothes made of synthetic fibers
  • Wearing cotton underwear and pantyhose with a cotton crotch
  • Changing out of wet swimsuits and exercise clothes as soon as possible
  • Avoiding hot tubs and very hot baths
  • Avoiding stress
  • Getting plenty of sleep
  • Eating well and avoiding sugary foods

References: 1. Penis health: identify and prevent problems. Mayo Clinic Web site. http://www.mayoclinic.org/healthy-lifestyle/mens-health/in-depth/penis-health/art-20046175. Updated April 8, 2016. Accessed October 30, 2018. 2. Vaginal yeast infections. Womenshealth.gov Web site. https://www.womenshealth.gov/a-z-topics/vaginal-yeast-infections. Updated May 24. 2018. Accessed October 30, 2018.

In 4 pooled 26-week placebo-controlled trials, patients taking INVOKANA® who experienced GMI were generally treated with oral or topical antifungal and antimicrobial agents.1

Reference: 1. INVOKANA® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.

Urinary tract infection (UTI)

In 4 pooled 26-week placebo-controlled studies, incidence of UTI was1:

  • 3.8% with placebo
  • 5.9% with INVOKANA® 100 mg
  • 4.4% with INVOKANA® 300 mg

The majority of UTIs in patients taking INVOKANA® were2:

  • Mild to moderate in severity
  • Lower UTIs

No UTIs led to trial discontinuation.

References: 1. INVOKANA® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 2. Stenlöf K, Cefalu WT, Kim KA, et al. Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetes Obes Metab. 2013;15(4):372-382.

Increased urination

In 4 pooled 26-week placebo-controlled trials, the incidence of increased urination, including polyuria, pollakiuria, increased urine output, micturition urgency, and nocturia, was1:

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

Reference: 1. INVOKANA® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.

Amputation

A 2-fold increased risk of lower-limb amputation with INVOKANA® was observed in CANVAS and CANVAS-R, 2 large, randomized controlled trials in patients with type 2 diabetes who had established cardiovascular disease or were at risk for cardiovascular disease.1

In the CANVAS Program, the amputation rate was 0.63 events/100 patient-years in the pooled INVOKANA® 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 cardiovascular disease or cardiovascular risk with INVOKANA® for a year led to an additional 0.3 events.2

Nearly all patients (92% to 96%) who experienced an amputation had one or more of the following identifiable precipitating events3: Prior amputation and/or

  • Severe lower-extremity infection
  • Gangrene
  • Diabetic foot ulcer
  • Acute limb ischemia

There was no greater increase in precipitating events with INVOKANA® vs placebo.2

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

References: 1. INVOKANA® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 2. 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. 3. Data on file. Janssen Pharmaceuticals, Inc., Titusville, NJ.

The finding of increased risk of lower-limb amputation was observed with INVOKANA® in the integrated analysis of the CANVAS Program, which included patients with type 2 diabetes who had established cardiovascular disease or were at risk for cardiovascular disease.1

A total of 187 patients (140/5790 on INVOKANA® and 47/4344 on placebo) had an atraumatic lower-limb amputation.2 In the CANVAS Program, the amputation rate was 0.63 events/100 patient-years in the pooled INVOKANA® 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 cardiovascular disease or cardiovascular risk with INVOKANA® for a year led to an additional 0.3 events.1

Other adverse events observed in the CANVAS Program were generally consistent with the known safety profile of INVOKANA®.1

The increase in amputation was not observed across 12 other completed phase 3 and 4 INVOKANA® clinical trials comprising >8100 patients with type 2 diabetes.2

References: 1. 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. 2. Data on file. Janssen Research and Development, LLC, Titusville, NJ.

Amputations of the toe and midfoot were the most frequent.1

Reference: 1. INVOKANA® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.

No dose response was observed.1

Reference: 1. INVOKANA® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.

The highest risk of lower-limb amputation across treatments was seen in patients with a baseline history of prior amputation, peripheral vascular disease, and neuropathy.1

Nearly all (92% to 96%) had identifiable precipitating events2: Prior amputation and/or

  • Severe lower-extremity infection
  • Gangrene
  • Diabetic foot ulcer
  • Acute limb ischemia

There was no greater increase in precipitating events with INVOKANA® vs placebo.3

References: 1. INVOKANA® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 2. Data on file. Janssen Research and Development, LLC, Titusville, NJ. 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.

Before initiating INVOKANA®, consider factors in the patient history that may predispose to the need for amputation, such as a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers.1

As with any patient with type 2 diabetes, examine their feet and counsel them about the importance of routine preventive foot care.

Monitor patients receiving INVOKANA® for signs and symptoms of infection (including osteomyelitis), new pain or tenderness, and sores or ulcers involving the lower limbs, and discontinue INVOKANA® if these complications occur.1

Reference: 1. INVOKANA® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.

This HCP-Patient Amputation Fact Sheet is designed to help patients understand who is at risk for amputation based on the results of the CANVAS Program.

Download the Amputation Fact Sheet for Patients

Facts about diabetic ketoacidosis (DKA)

Incidence of serious DKA adverse events and related events1

Overall

 

Non-INVOKANA® (n=6909)

INVOKANA® 100 mg (n=5337)

INVOKANA® 300 mg (n=5350)

Total (N=17,596)

Incidence (%)

0.03

0.07

0.11

0.07

Incidence rate, per 1000 patient-years

0.238

0.522

0.763

N/A

Excluding autoimmune diabetes*

 

Non-INVOKANA® (n=6909)

INVOKANA® 100 mg (n=5334)

INVOKANA® 300 mg (n=5347)

Total (n=17,590)

Incidence (%)

0.03

0.02

0.06

0.03

Incidence rate, per 1000 patient-years

0.238

0.130

0.381

N/A

*After being diagnosed with a DKA-related event, 6 patients on INVOKANA® (3 patients in the INVOKANA® 100 mg group, 3 patients in the INVOKANA® 300 mg group) were reported to have autoimmune diabetes (LADA or T1DM) or tested positive for GAD65 antibodies.

  • In the 17,596 patients included in the analysis, 12 patients overall had a DKA-related adverse event1:
    • The incidence was less than 0.1% overall, with events occurring both in patients on INVOKANA® and patients not on INVOKANA®
  • Additional analyses of the 12 patients revealed that 6 patients, all treated with INVOKANA®, had undiagnosed T1DM or LADA, or tested positive for GAD65 antibodies. When we exclude these patients from the original analysis, the incidence of DKA-related AEs is similar across treatment groups1

GAD65=glutamic acid decarboxylase; LADA=latent autoimmune diabetes of adulthood; T1DM=type 1 diabetes mellitus.

Reference: 1. Erondu N, Desai M, Ways K, Meininger G. Diabetic ketoacidosis and related events in the canagliflozin type 2 diabetes clinical program. Diabetes Care. 2015;38(9):1680-1686.

Drug-drug interactions

  • Coadministration of drugs that induce UGT (UDP-glucuronosyl transferase) enzymes, such as rifampin, which is used to treat conditions such as tuberculosis and Neisseria meningitidis, may decrease the efficacy of INVOKANA®1,2
    • Monitor A1C and consider increasing the dosage of INVOKANA® to 300 mg once daily if patients are tolerating INVOKANA® 100 mg, have an eGFR =60 mL/min/1.73 m2, and require additional glycemic control1
  • Coadministration of INVOKANA® 300 mg with digoxin, which is used to treat conditions such as heart failure and arrhythmias, may increase digoxin concentration.1,3 Patients taking INVOKANA® and digoxin should be monitored appropriately1
  • Monitoring glycemic control with urine glucose tests and 1,5-AG (anhydroglucitol) assays is not recommended in patients taking INVOKANA®; use alternative methods to monitor glycemic control1:
    • Urine glucose tests: SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests
    • 1,5-AG assays: Measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors

SGLT2=sodium-glucose co-transporter 2.

References: 1. INVOKANA® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 2. Rifampin. MedlinePlus Web site. http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682403.html. Updated February 15, 2018. Accessed October 30, 2018. 3. Digoxin oral. MedlinePlus Web site. http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682301.html. Updated June 15, 2017. Accessed October 30, 2018.

Hypoglycemia

Insulin and insulin secretagogues are known to cause hypoglycemia. INVOKANA® can increase the risk of hypoglycemia when combined with insulin or an insulin secretagogue. Therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with INVOKANA®.1

Reference: 1. INVOKANA® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.

In all clinical trials of INVOKANA®, hypoglycemia was defined as any event, regardless of symptoms, where biochemical hypoglycemia was documented (any glucose value =70 mg/dL) or any hypoglycemic episode considered severe.1

Severe hypoglycemia was defined as an event consistent with hypoglycemia where the patient required the assistance of another person to recover, lost consciousness, or experienced a seizure (regardless of whether biochemical documentation of a low glucose value was obtained).1

Reference: 1. INVOKANA® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.

Renal threshold for glucose

Renal glucose reabsorption takes place primarily via sodium-glucose co-transporter 2 (SGLT2).1 The renal threshold for glucose (RTG) is the plasma glucose concentration at which tubular reabsorption of glucose begins to saturate; glucose is excreted into the urine in direct proportion to the glucose concentration above this threshold. Patients with diabetes have been shown to have elevated renal glucose reabsorption, which may contribute to persistent elevated plasma glucose concentrations.2

By inhibiting SGLT2, INVOKANA®1:

  • Reduces the reabsorption of filtered glucose
  • Lowers the renal threshold for glucose in patients with type 2 diabetes from 240 mg/dL to 70-90 mg/dL
  • Increases urinary glucose excretion

Learn more about how INVOKANA® impacts the renal threshold for glucose in patients with type 2 diabetes.

References: 1. INVOKANA® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 2. Devineni D, Curtin CR, Polidori D, et al. Pharmacokinetics and pharmacodynamics of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in subjects with type 2 diabetes mellitus. J Clin Pharmacol. 2013;53(6):601-610.