canagliflozin (Rx)

Brand and Other Names:Invokana
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 100mg
  • 300mg
more...

Diabetes Mellitus Type 2

Selective sodium-glucose transporter-2 (SGLT2) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control with type 2 diabetes mellitus

Initial: 100 mg PO qDay taken before the first meal of the day

May increase dose to 300 mg qDay in patients tolerating 100 mg/day who have an eGFR ≥60 mL/min/1.73 m² and require additional glycemic control

Dosage Modifications

Renal impairment

  • eGFR ≥60 mL/min/1.73 m²: No dosage adjustment required
  • eGFR 45 to <60 mL/min/1.73 m²: Do not exceed 100 mg/day
  • eGFR <45 mL/min/1.73 m²: Do not initiate canagliflozin
  • Not recommended with eGFR that declines persistently below 45 mL/min/1.73 m²
  • eGFR <30 mL/min/1.73 m²: Contraindicated

UGT enzyme inducers

  • Coadministration with UGT enzyme inducers (eg, rifampin, phenytoin, phenobarbital, ritonavir): Consider increasing dose to 300 mg qDay in patients tolerating 100 mg/day with eGFR ≥60 mL/min/1.73 m² and require additional glycemic control
  • Consider another antihyperglycemic agents if eGFR is 45 to <60 mL/min/1.73 m² and receiving a UGT inducer

Dosing Considerations

Not recommended for treating type 1 diabetes mellitus or diabetic ketoacidosis

Correct volume depletion prior to initiating canagliflozin

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and canagliflozin

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            Adverse Effects

            >10%

            Female genital mycotic infections (10.4-11.4%)

            1-10%

            Increased urination (4.6-5.3%)

            Male genital mycotic infections (3.7-4.2%)

            Vulvovaginal pruritus (1.6-3%)

            Thirst (2.3-2.8%)

            Constipation (1.8-2.3%)

            Nausea (2.2-2.3%)

            Abdominal pain (1.7-1.8%)

            Volume depletion

            • Overall population (2.3-3.4%)
            • Age >75 yr (4.9-8.7%)
            • eGFR <60/mL/min/1.73 m³ (4.7-8.1%)
            • Use of loop diuretic (3.2-8.8%)

            Postmarketing reports

            Bone fractures

            Higher risk of falls for patients treated within first few weeks of treatment reported

            Anaphylaxis

            Angioedema

            Previous
            Next:

            Warnings

            Black Box Warnings

            Lower limb amputation

            • An approximately 2-fold increased risk of lower limb amputations associated with canagliflozin use was observed in 2 large, randomized, placebo-controlled trials (CANVAS AND CANVAS-R) in patients with type 2 diabetes who had established cardiovascular disease (CVD) or were at risk for CVD
            • Amputations of the toe and midfoot were most frequent; however, amputations involving the leg were also observed; some patients had multiple amputations, some involving both limbs
            • Before initiating, consider factors that may increase the risk of amputation (eg, history of prior amputation, peripheral vascular disease, neuropathy, diabetic foot ulcers)
            • Monitor patients for infection, new pain or tenderness, and sores or ulcers involving the lower limbs; discontinue if these complications occur
            • Counsel patients about importance of routine preventative foot care

            Contraindications

            Documented hypersensitivity

            Severe renal impairment (eGFR <30 mL/min/1.73 m²), end-stage renal disease or patients on dialysis

            History of a serious hypersensitivity reaction to canagliflozin, such as anaphylaxis or angioedema

            Cautions

            Causes intravascular volume contraction and symptomatic hypotension and/or acute kidney injury can occur, particularly if eGFR <60 mL/min/1.73 m², advance age, existing low systolic BP, or taking either diuretics or drugs that interfere with renin-angiotensin-aldosterone system (RAS) (eg, ACE inhibitors, ARBs); before initiating therapy, assess volume status and correct hypovolemia in patients with renal impairment, the elderly, in patients with low systolic blood pressure, or on diuretics, ACE inhibitors, or ARB; monitor for signs and symptoms during therapy

            An approximately 2-fold increased risk of lower limb amputations associated with canagliflozin use was observed in 2 large clinical trials; lower limb infections, gangrene, and diabetic foot ulcers were the most common precipitating medical events leading to the need for an amputation; risk of amputation was highest with baseline history of prior amputation, peripheral vascular disease, and neuropathy (see Black Box Warnings)

            Drug increases serum creatinine and decreases eGFR, patients with hypovolemia are more susceptible to renal function impairment

            Consider temporarily discontinuing in settings of reduced oral intake or fluid losses; if acute kidney injury occurs, discontinue and promptly treat; monitor renal function during therapy

            Hyperkalemia reported; patients with moderate renal impairment who take potassium-sparing diuretics or drugs that alter RAS are more likely to develop hyperkalemia; monitor potassium levels in patients with impaired renal function and in patients predisposed to hyperkalemia

            Hypoglycemia risk increased with insulin and insulin secretagogues, consider a lower dose of insulin or the insulin secretagogue

            Genital mycotic infections may occur, patients with history of genital mycotic infections and uncircumcised males are more susceptible

            Increases risk of urinary tract infections (UTIs), including life-threatening urosepsis and pyelonephritis that started as UTIs; evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated

            Ketoacidosis associated with SGLT2 inhibitors reported; monitor for signs of ketoacidosis and advise patients to seek immediate medical attention for symptoms (eg, difficulty breathing, nausea, vomiting, abdominal pain, confusion, unusual fatigue or sleepiness); assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level; consider risk factors for ketoacidosis prior to initiating therapy; patients may require temporary discontinuation of therapy in clinical situation that may predispose to ketoacidosis

            Causes intravascular volume contraction and can cause renal impairment; acute kidney injury, some requiring hospitalization and dialysis reported

            Before initiating therapy, consider factors that may predispose patients to acute kidney injury including hypovolemia, chronic renal insufficiency, congestive heart failure, and concomitant medications (diuretics, ACE inhibitors, ARBs, NSAIDs); consider temporarily discontinuing therapy in any setting of reduced oral intake (such as acute illness or fasting) or fluid losses (such as gastrointestinal illness or excessive heat exposure)

            Before initiating therapy, obtain an estimated glomerular filtration rate and obtain an eGFR at least annually; assess more frequently in patients at increased risk for development of renal impairment

            Hypersensitivity reactions (eg, generalized urticaria), some serious, were reported during clinical trials; if it occurs, discontinue therapy and monitor until signs and symptoms resolve

            Dose-related increases in LDL-C reported; monitor LDL-C and treat if appropriate

            No conclusive evidence of macrovascular risk reduction with canagliflozin or any other antidiabetic agent exists

            SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests; use alternative methods to monitor glycemic control

            Increased risk of bone fracture, occurring as early as 12 weeks after treatment initiation, reported; consider factors that contribute to fracture risk prior to initiating therapy

            Higher risk of falls for patients treated within first few weeks of treatment reported

            Hypersensitivity reactions, including angioedema and anaphylaxis reported with canagliflozin; these reactions generally occurred within hours to days after initiating canagliflozin; if hypersensitivity reactions occur, discontinue therapy; treat and monitor until signs and symptoms resolve

            Not recommended for use in severe hepatic impairment (not studied); dose adjustment not necessary in mild or moderate hepatic impairment

            Should not be used for the treatment of patients with type 1 diabetes mellitus (insulin dependent)

            Previous
            Next:

            Pregnancy & Lactation

            Pregnancy Category: C

            Lactation: Unknown whether distributed in human breast milk; breast feeding women should discontinue canagliflozin or nursing taking into account the importance of the drug to the mother

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

            more...
            Previous
            Next:

            Pharmacology

            Mechanism of Action

            Selective sodium-glucose transporter-2 (SGLT2) inhibitor

            SGLT-2 inhibition lowers the renal glucose threshold (ie, the plasma glucose concentration which exceed the maximum glucose reabsorption capacity of the kidney); lowering the renal glucose threshold results in increased urinary glucose excretion

            Absorption

            Bioavailability: 65%

            Peak plasma time: 1-2 hr

            Distribution

            Protein bound: 99% (predominantly to albumin)

            Vd: 119 L

            Metabolism

            O-glucuronidation is the major metabolic elimination pathway, mainly by UGT1A9 and UGT2B4 to 2 inactive O-glucuronide metabolites

            CYP3A4-mediated (oxidative) metabolism is minimal (~7%)

            Elimination

            Half-life: 10.6 hr (100 mg dose); 13.1 hr (300 mg dose)

            Total body clearance: 192 mL/min

            Excretion

            • Feces: 41.5% (canagliflozin), 7% (hydroxylated metabolite), 3.2% (O-glucuronide metabolite)
            • Urine: 33% excreted in urine, mainly as O-glucuronide metabolites (30.5%); <1% excreted unchanged
            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous