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Invokamet Side Effects

Generic Name: canagliflozin / metformin

Note: This document contains side effect information about canagliflozin / metformin. Some of the dosage forms listed on this page may not apply to the brand name Invokamet.

In Summary

Common side effects of Invokamet include: lactic acidosis, vulvovaginal candidiasis, vaginal infection, vulvitis, and vulvovaginitis. Other side effects include: cyanocobalamin deficiency, balanitis, balanoposthitis, increased urine output, nocturia, polyuria, urinary urgency, and pollakiuria. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to canagliflozin / metformin: oral tablet, oral tablet extended release

Along with its needed effects, canagliflozin / metformin may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking canagliflozin / metformin:

More common
  • Abdominal or stomach discomfort
  • bladder pain
  • bloody or cloudy urine
  • decreased appetite
  • diarrhea
  • difficult, burning, or painful urination
  • fast, shallow breathing
  • frequent urge to urinate
  • frequent urination
  • general feeling of discomfort
  • increased urge to urinate during the night
  • increased volume of pale, dilute urine
  • itching of the vagina or genitals
  • itching, stinging, or redness of the vaginal area
  • lower back or side pain
  • muscle pain or cramping
  • nausea
  • shortness of breath
  • sleepiness
  • thick, white vaginal discharge with mild or no odor
  • unusual tiredness or weakness
  • waking to urinate at night
Less common
  • Dry mouth
  • increased thirst
Incidence not known
  • Anxiety
  • blurred vision
  • chills
  • cold sweats
  • coma
  • confusion
  • cool, pale skin
  • depression
  • difficulty with swallowing
  • dizziness
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • fast heartbeat
  • fever
  • headache
  • hives
  • increased hunger
  • irregular heartbeat
  • nightmares
  • numbness or tingling in the hands, feet, or lips
  • pain in the skin around the penis
  • reddening of the skin, especially around the ears
  • redness, itching, or swelling of the penis
  • seizures
  • shakiness
  • slurred speech
  • stomach pain
  • sweating
  • swelling of the eyes, face, or inside of the nose
  • vomiting
  • weakness or heaviness of the legs

Some side effects of canagliflozin / metformin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common
  • Difficulty having a bowel movement (stool)

For Healthcare Professionals

Applies to canagliflozin / metformin: oral tablet, oral tablet extended release

General

Canagliflozin:
-The most commonly reported adverse reactions included hypoglycemia in combination with insulin or a sulfonylurea, vulvovaginal candidiasis, urinary tract infection, polyuria or pollakiuria.

Metformin:
- The most commonly reported adverse reactions included diarrhea, nausea, vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache.[Ref]

Musculoskeletal

In the CANVAS trial, amputations per 1000 patients per year in patients receiving canagliflozin (100 mg or 300 mg per day) were 5.8 compared to 2.8 amputations per 1000 patients per year in the placebo group. In the CANVAS-R trials, these numbers were 7.5 and 4.2, respectively. The total number of amputations among canagliflozin-treated patients (n=5790) was 221 compared with 69 in the placebo group (n=4344). Amputations of the toe and midfoot were the most frequent; however, amputations involving the leg, below and above the knee, also occurred.

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. 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]

Canagliflozin:
Common (1% to 10%): Lower limb amputations
Frequency not reported: Bone fracture, upper extremity fracture, loss of bone mineral density at hip and lower spine[Ref]

Genitourinary

Canagliflozin:
Very common (10% or more): Female genital mycotic infections (up to 11.4%)
Common (1% to 10%): Urinary tract infections, increased urination, male genital mycotic infections, vulvovaginal pruritus[Ref]

Cardiovascular

Volume depletion-related reactions included hypotension, postural dizziness, orthostatic hypotension, syncope, and dehydration.[Ref]

Canagliflozin:
Common (1% to 10%): Volume depletion-related reactions[Ref]

Metabolic

Canagliflozin:
Very common (10% or more): Elevated serum potassium, elevated serum magnesium, elevated serum phosphate
Common (1% to 10%): Increased low-density lipoprotein cholesterol, increased non-high-density lipoprotein cholesterol
Postmarketing reports: Acidosis including diabetic ketoacidosis, ketoacidosis, or ketosis

Metformin:
Very rare (less than 0.01%): Lactic acidosis, vitamin B12 deficiency[Ref]

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]

Renal

Canagliflozin:
Common (1% to 10%): Renal function decline
Frequency not reported: Increased serum creatinine increases, decreased GFR
Postmarketing reports: Acute kidney injury, renal function impairment, urosepsis, pyelonephritis[Ref]

Hepatic

Metformin:
Very rare (less than 0.01%): Liver function disorders, liver function tests abnormalities, hepatitis[Ref]

Endocrine

Canagliflozin:
Very common (10% or more): Hypoglycemia in combination with insulin or sulfonylurea[Ref]

Hypersensitivity

Hypersensitivity-related reactions included erythema, rash, pruritus, urticaria, and angioedema.[Ref]

Canagliflozin:
Common (1% to 10%): Hypersensitivity-related reactions
Postmarketing reports: Anaphylaxis, angioedema[Ref]

Gastrointestinal

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

Hematologic

Canagliflozin:
Common (1% to 10%): Increased hemoglobin[Ref]

Other

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

Final results from 2 clinical trials, the CANVAS (Canagliflozin Cardiovascular Assessment Study) and the CANVAS-R (A Study of the Effects of Canagliflozin on Renal Endpoints in Adult Participants with Type 2 Diabetes Mellitus) have shown leg and foot amputations occurred almost twice as often in canagliflozin treated patients compared with placebo treated patients. Amputations of the toe and middle of the foot were most common, however some amputations involved the leg, below and above the knee. Some patients had more than 1 amputation; some involved both limbs.

The risk of amputation calculated from the CANVAS trial showed 5.9 per 1000 patients per year for canagliflozin treated patients compared to 2.8 per 1000 patients per year for placebo patients. The CANVAS-R trial showed 7.5 per 1000 patients per year compared to 4.2 per 1000 patients per year for canagliflozin treated patients and placebo patients, respectively.[Ref]

Dermatologic

Rash includes erythematous, generalized, macular, maculopapular, papular, pruritic, pustular and vesicular rashes.[Ref]

Canagliflozin:
Uncommon (0.1% to 1%): Rash, urticaria, photosensitivity-related reactions

Metformin:
Very rare (less than 0.01%): Urticaria, erythema, pruritus[Ref]

Nervous system

Metformin:
Common (1% to 10%): Taste disturbance[Ref]

References

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

2. "Product Information. Invokamet (canagliflozin-metFORMIN)." Janssen Pharmaceuticals, Titusville, NJ.

3. 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):

4. 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]):

5. US Food and Drug Administration "FDA Drug Safety Communication: FDA confirms increased risk of leg and foot amputations with the diabetes medicine canagliflozin (Invokana, Invokamet, Invokamet XR) Available from: URL: https://www.fda.gov/Drugs/DrugSafety/ucm557507.htm?source=govdelivery&" ([2017, May 16]):

Some side effects of Invokamet may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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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