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Invokana Side Effects

Generic Name: canagliflozin

Note: This page contains information about the side effects of canagliflozin. Some of the dosage forms included on this document may not apply to the brand name Invokana.

In Summary

Common side effects of Invokana include: vulvovaginal candidiasis, vulvovaginitis, vulvitis, vaginal infection, and mean glomerular filtration rate decreased. Other side effects include: nocturia, polyuria, urinary urgency, balanoposthitis, balanitis, increased urine output, and pollakiuria. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to canagliflozin: oral tablet

In addition to its needed effects, some unwanted effects may be caused by canagliflozin (the active ingredient contained in Invokana). In the event that any of these side effects do occur, they may require medical attention.

Major Side Effects

You should check with your doctor immediately if any of these side effects occur when taking canagliflozin:

More common:
  • Bladder pain
  • bloody or cloudy urine
  • decreased frequency or amount of urine
  • difficult, burning, or painful urination
  • discharge with a strong odor from the penis
  • frequent urge to urinate
  • increased blood pressure
  • increased thirst
  • itching of the vagina or outside of the genitals
  • loss of appetite
  • lower back or side pain
  • nausea
  • pain during sexual intercourse
  • pain in the skin around the penis
  • redness, itching, or swelling of the penis
  • swelling of the face, fingers, or lower legs
  • troubled breathing
  • unusual tiredness or weakness
  • vaginal discharge without odor or with mild odor
  • vomiting
  • weight gain
Less common:
  • Anxiety
  • blurred vision
  • chills
  • cold sweats
  • confusion
  • cool, pale skin
  • depression
  • dizziness
  • dry mouth
  • fast or irregular heartbeat
  • headache
  • hives or welts
  • increased hunger
  • itching skin
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • nightmares
  • rash
  • redness of the skin
  • seizures
  • shakiness
  • slurred speech
  • unusual tiredness or weakness
Incidence not known:
  • Abdominal or stomach pain
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • numbness or tingling in the hands, feet, or lips
  • sweating
  • weakness or heaviness of the legs

Minor Side Effects

Some of the side effects that can occur with canagliflozin may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

Less common:
  • Difficulty having a bowel movement (stool)
  • lack or loss of strength
  • pain or swelling in the arms or legs without an injury
Rare
  • Increased sensitivity of the skin to sunlight
  • redness or other discoloration of the skin
  • severe sunburn

For Healthcare Professionals

Applies to canagliflozin: oral tablet

General

The most commonly reported adverse reactions were hypoglycemia when used in combination with insulin or an insulin secretagogue, vulvovaginal candidiasis, urinary tract infection, and increased urinary frequency.[Ref]

Genitourinary

Very common (10% or more): Female genital mycotic infections including vulvovaginal mycotic infection, vulvovaginitis, vaginal infection, vulvitis, and genital infection fungal (up to 11.4%), recurrent male genital mycotic infections (22%)
Common (1% to 10%): Urinary tract infection, increased urination, male genital mycotic infections including balanitis, balanoposthitis, balanitis candida, and fungal genital infection
Uncommon (0.1% to 1%): Phimosis
Postmarketing reports: Urosepsis, pyelonephritis[Ref]

Cardiovascular

Common (1% to 10%): Adverse reactions related to reduced intravascular volume (postural hypotension, orthostatic hypotension, hypotension, dehydration, and syncope)[Ref]

Metabolic

Twenty reports of acidosis have been identified in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database during the period March 2013 through 06 June 2014. All patients required emergency room treatment or hospitalization. These cases were not typical of ketoacidosis or diabetic ketoacidosis (DKA) in that they occurred in patients with type 2 diabetes and their blood sugar levels were only slightly increased. Some factors identified as potentially triggering the acidosis included major illness, reduced food and fluid intake, and reduced insulin dose.[Ref]

Very common (10% or more): Hypoglycemia when combined with insulin or an insulin secretagogue (up to 49%), hyperkalemia (up to 27%)
Common (1% to 10%): Increased serum magnesium, increased serum phosphate, increased low-density lipoprotein (LDL-C)
Postmarketing reports: Acidosis including diabetic ketoacidosis, ketoacidosis, or ketosis[Ref]

Gastrointestinal

Common (1% to 10%): Constipation, thirst, nausea, abdominal pain, pancreatitis[Ref]

Musculoskeletal

In a pooled analysis of 9 clinical trials with a mean duration drug exposure of 85 weeks, the incidence rate of adjudicated bone fractures were 1.1, 1.4, 1.5 per 100 patient years of exposure to the comparator, 100 or 300 mg dose, respectively. Fractures were observed as early as 12 weeks and were more likely to be caused by low trauma and affect upper extremities.

On September 10, 2015, the US Food and Drug Administration issued a drug safety communication regarding new information on bone fracture risk and decreased bone mineral density with use of canagliflozin (the active ingredient contained in Invokana) Based on updated data, fractures have occurred as early as 12 weeks after starting therapy with trauma that is usually minor, such as falling from standing height. Additionally, a 2-year study (n=714) has shown a greater loss of bone mineral density at the hip and lower spine in canagliflozin treated patients compared with placebo.[Ref]

Uncommon (0.1% to 1%): Bone fracture, upper extremity fracture
Frequency not reported: Loss of bone mineral density at hip and lower spine[Ref]

Hypersensitivity

Common (1% to 10%): Hypersensitivity reactions including rash, pruritus, urticaria, and angioedema
Frequency not reported: Serious hypersensitivity reaction
Postmarketing reports: Anaphylaxis[Ref]

Renal

Frequency not reported: Increases in serum creatinine, decreases in eGFR, renal impairment, acute renal failure
Postmarketing reports: Acute kidney injury[Ref]

In a pooled analysis among patients with moderate renal impairment, the incidence of renal related adverse reactions such as increased serum creatinine, decreased eGFR, renal impairment, or acute renal failure, was 8.9% and 9.3% in patients receiving canagliflozin 100 mg or 300 mg, compared with 3.7% in those receiving comparator drug or placebo.

From March 2013 to October 2015, the US FDA received 101 confirmable case reports of acute kidney injury (AKI) with use of canagliflozin (n=73) or dapagliflozin (n=28). Hospitalization was necessary for evaluation and management in 96 cases; admission to the intensive care unit occurred in 22 cases, and death occurred in 4 patients, of which 2 were cardiac-related. Dialysis was necessary in 15 patients, 3 of whom had a history of chronic kidney disease or previous AKI. In 58 cases, time to onset of AKI was within 1 month or less of initiating therapy. In 78 cases in which drug discontinuation was reported, 56 reported subsequent improvement; 3 patients recovered with sequelae, 11 patients did not recover (including the 4 deaths mentioned earlier). Median age was 57 years (range 28 to 78 years; based on 84 cases reporting age). Concomitant ACE inhibitor therapy was reported in 51 cases, diuretic use in 26 cases, and NSAID use in 6 cases. Almost half the patients reported a change in renal function at time of diagnosis (median elevation of serum creatinine from baseline 1.6 mg/dL [based on 32 cases reporting serum creatinine] and median decrease in eGFR 46 mL/min/1.73m2 [based on 13 cases reporting eGFR]).[Ref]

Dermatologic

Uncommon (0.1% to 1%): Photosensitivity reactions, rash, urticaria[Ref]

Other

The US FDA has issued a safety alert warning of increased leg and foot amputations (mostly toes) compared to placebo in the ongoing CANVAS (Canagliflozin (the active ingredient contained in Invokana) Cardiovascular Assessment Study) clinical trial. Interim safety results have shown risk of amputation for patients receiving 100 mg daily, 300 mg daily, and placebo were 7, 5, and 3 out of 1000 patients treated, respectively based on an average follow-up of 4.5 years. A similar trial (CANVAS-R) trial has not shown these risks (average follow-up 9 months). The FDA will continue to evaluate this safety issue and update as necessary.[Ref]

Common (1% to 10%): Fatigue, asthenia, falls
Uncommon (0.1% to 1%): Leg and foot amputations[Ref]

References

1. Cerner Multum, Inc. "Australian Product Information." O 0

2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

3. "Product Information. Invokana (canagliflozin)." Janssen Pharmaceuticals, Titusville, NJ.

4. FDA. U.S. Food and Drug Administration "FDA: SGLT2 inhibitors: Drug Safety Communication - FDA Warns Medicines May Result in a Serious Condition of Too Much Acid in the Blood Available from: URL: http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm44699" (2015 May 15):

5. US Food and Drug Administration "Invokana and Invokamet (canagliflozin): Drug Safety Communication - New Information on Bone Fracture Risk and Decreased Bone Mineral Density. Available from: URL: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm" ([2015, Sep. 10]):

6. US Food and Drug Administration "Canagliflozin (Invokana, Invokamet) and Dapagliflozin (Farxiga, Xigduo XR): Drug Safety Communication - Strengthened Kidney Warnings. Available from: URL: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm506554.h" ([2016, Jun 14]):

7. FDA. U.S. Food and Drug Administration "FDA Drug Safety Communication: Interim clinical trial results find increased risk of leg and foot amputations, mostly affecting the toes, with the diabetes medicine canagliflozin (Invokana, Invokamet); FDA to investigate. Available from: URL: http://www.f" ([2016, May 18]):

Not all side effects for Invokana may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the substances you are taking, check with your doctor, nurse, or pharmacist.

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