Invokamet XR Side Effects

Generic name: canagliflozin / metformin

Medically reviewed by Drugs.com. Last updated on Jul 21, 2024.

Note: This document provides detailed information about Invokamet XR Side Effects associated with canagliflozin / metformin. Some dosage forms listed on this page may not apply specifically to the brand name Invokamet XR.

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

Precautions

It is very important that your doctor check your progress at regular visits, especially during the first few weeks that you take this medicine. Blood and urine tests may be needed to check for unwanted effects.

Using this medicine during the second and third part of your pregnancy can harm your unborn baby. If you think you have become pregnant while using this medicine, tell your doctor right away.

This medicine may cause some women who do not have regular monthly periods to ovulate. This can increase the chance of pregnancy. If you are a woman of childbearing potential, you should discuss birth control options with your doctor.

It is very important to follow carefully any instructions from your doctor about:

• Alcohol—Drinking alcohol may cause severe low blood sugar. Discuss this with your doctor.
• Other medicines—Do not take other medicines unless they have been discussed with your doctor. This especially includes nonprescription medicines such as aspirin, and medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems.
• Counseling—Other family members need to learn how to prevent side effects or help with side effects if they occur. Also, patients with diabetes may need special counseling about the changes in the dosing of their diabetes medicine that might occur because of lifestyle changes, such as changes in exercise and diet. Furthermore, counseling on contraception and pregnancy may be needed because of the problems that can occur in patients with diabetes during pregnancy.
• Travel—Keep a recent prescription and your medical history with you. Be prepared for an emergency as you would normally. Make allowances for changing time zones and keep your meal times as close as possible to your usual meal times.
• In case of emergency—There may be a time when you need emergency help for a problem caused by your diabetes. You need to be prepared for these emergencies. It is a good idea to wear a medical identification (ID) bracelet or neck chain at all times. Also, carry an ID card in your wallet or purse that says that you have diabetes and a list of all of your medicines.

Under certain conditions, too much metformin can cause a serious condition, called lactic acidosis. The symptoms of lactic acidosis are severe and appear quickly. Lactic acidosis usually occurs when other serious health problems are present, such as a heart attack or kidney failure. The symptoms of lactic acidosis include: stomach discomfort, decreased appetite, diarrhea, fast or shallow breathing, a general feeling of discomfort, muscle pain or cramping, and unusual sleepiness, tiredness, or weakness. If you have more than one of these symptoms together, you should get emergency medical help right away.

This medicine may increase your risk of having leg, toe, or midfoot amputation (leg removal surgery). Check with your doctor right away if you have pain, tenderness, sores or ulcers, or infections on your leg or foot.

Dizziness, lightheadedness, or fainting may occur with this medicine. This is more common if you have kidney disease, low blood pressure, or if you are taking a diuretic (water pill). Taking plenty of fluids each day may help. Drink plenty of water during exercise or in hot weather. Check with your doctor if you have severe nausea, vomiting, or diarrhea that does not stop. This may cause you to lose too much water.

Ketoacidosis (high ketones and acid in the blood) may occur while you are using this medicine. This can be life-threatening and requires immediate medical attention. Your doctor may give you insulin, fluid, and carbohydrate replacement to treat this condition. Tell your doctor right away if you have nausea, vomiting, trouble breathing, increased thirst or urination.

Check with your doctor right away if you have bloody urine, decrease in how much or how often you urinate, an increase in blood pressure, increased thirst, loss of appetite, lower back or side pain, nausea, swelling of the face, fingers, or lower legs, trouble breathing, unusual tiredness or weakness, vomiting, or weight gain. These could be symptoms of a serious kidney problem.

This medicine may cause vaginal yeast infections in women and yeast infections of the penis in men. This is more common in patients who have a history of genital yeast infections or in men who are not circumcised. Women may have a vaginal discharge, itching, or odor. Men may have redness, itching, swelling, or pain around the penis, or a discharge with a strong odor from the penis. Check with your doctor right away if you have any of these symptoms.

This medicine may increase risk of having urinary tract infections, including pyelonephritis or urosepsis. Check with your doctor right away if you have bladder pain, bloody or cloudy urine, difficult, burning, or painful urination, or lower back or side pain.

This medicine may cause serious allergic reactions, including anaphylaxis or angioedema. These reactions can be life-threatening and require immediate medical attention. Call your doctor right away if you have a rash, itching, blistering, peeling, or loosening of the skin, fever or chills, trouble breathing or swallowing, or any swelling of your hands, face, mouth, or throat while you are using this medicine.

This medicine may cause a rare but serious bacterial infection, called necrotizing fasciitis of the perineum or Fournier's gangrene, which can cause damage to the tissue under the skin in the area between and around the anus and genitals (perineum). Fournier's gangrene may lead to hospitalization, multiple surgeries, or death. Check with your doctor right away if you have fever, unusual tiredness or weakness, or pain, tenderness, redness, or swelling of the area between and around your anus and genitals.

Do not drink a lot of alcohol while you are using this medicine. Heavy alcohol use can increase your risk for lactic acidosis.

This medicine may increase the risk of bone fractures. Ask your doctor about ways to keep your bones strong to help prevent fractures.

This medicine may cause hypoglycemia (low blood sugar). This is more common when this medicine is taken together with other diabetes medicines (eg, insulin, glipizide, or glyburide). Low blood sugar must be treated before it causes you to pass out (unconsciousness). People feel different symptoms of low blood sugar. It is important that you learn which symptoms you usually have so you can treat it quickly. Talk to your doctor about the best way to treat low blood sugar.

Hyperglycemia (high blood sugar) may occur if you do not take enough or skip a dose of your diabetes medicine, overeat, or do not follow your diet plan, have a fever or infection, or do not exercise as much as usual. Some symptoms of high blood sugar include: blurred vision, drowsiness, dry mouth, flushed and dry skin, a fruit-like breath odor, increased frequency and amount of urination, ketones in the urine, loss of appetite, nausea or vomiting, rapid and deep breathing, tiredness, or unusual thirst. If symptoms of high blood sugar occur, check your blood sugar level and call your doctor for instructions.

Let your doctor or dentist know you are taking this medicine. Your doctor may advise you to Stop taking canagliflozin / metformin before you have major surgery or diagnostic tests, especially tests with contrast dye.

Make sure any doctor or dentist who treats you knows that you are using this medicine. This medicine may affect the results of certain medical tests (eg, urine glucose tests may not be accurate).

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Serious side effects of Invokamet XR

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:

Other side effects of Invokamet XR

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:

For healthcare professionals

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

General adverse events

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

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]

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]

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
• Postmarketing reports: Fournier's gangrene^[Ref]

In the 5 years (2013 to 2018) since SGLT2 inhibitor approval, 12 cases of Fournier's gangrene have been reported. Reports were almost equal in men and women (men=7; women=5), ages ranged from 38 to 78 years, and the average time to onset after starting an SGLT2 inhibitor was 9.2 months (range 7 days to 25 months). All SGLT2 inhibitor drugs except ertugliflozin were included in the reports. Ertugliflozin being the most recently approved agent, is expected to have the same risk, but insufficient patient use to assess risk. All patients were hospitalized, all required surgery, all required surgical debridement, 5 required more than 1 surgery and 1 required skin grafting. Four cases were complicated by diabetic ketoacidosis, acute kidney injury, and septic shock, leading to prolonged hospitalization, and death in 1 case. In the general population, Fournier's gangrene occurs in about 1.6 out of 100,000 males annually, with the highest incidence in men 50 to 79 years. Since diabetes is a risk factor for Fournier's gangrene, a review of the FAERS database for the last 34 years was done and only 6 cases (all males, median age 57 years) were found with several other classes of antidiabetic drugs. Findings with SGLT2 inhibitors appear to show an association over a shorter time frame and involve both males and females.^[Ref]

Cardiovascular

Canagliflozin:

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

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

Canagliflozin:

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

Hypersensitivity-related reactions included erythema, rash, pruritus, urticaria, and 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

Canagliflozin:

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

Metformin:

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

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

Nervous system

Metformin:

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

See also:

Further information

Invokamet XR side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Note: Medication side effects may be underreported. If you are experiencing side effects that are not listed, submit a report to the FDA by following this guide.

Medical Disclaimer