- Side Effects
- Drug Interactions
- Warnings and Precautions
What Is Canagliflozin and How Does It Work?
- Canagliflozin is available under the following different brand name: Invokana.
What Are Dosages of Canagliflozin?
Type 2 Diabetes Mellitus
- Initial: 100 mg orally once daily taken before the first meal of the day
- May increase dose to 300 mg once daily if 100 mg/day tolerated in patients who have eGFR over or 60 mg/mL/min/1.73 m2 and require additional glycemic control
Dosage Considerations – Should be Given as Follows:
- See "Dosages."
What Are Side Effects Associated with Using Canagliflozin?
Common side effects of Canagliflozin include:
- genital infections, and
- urinating more than usual
Serious side effects of Canagliflozin include:
- difficulty breathing,
- swelling of the face, lips, tongue, or throat,
- burning, itching, odor, discharge, pain, tenderness, redness or swelling of the genital or rectal area,
- feeling unwell,
- little or no urination,
- pain or burning while passing urine,
- new pain, tenderness, sores, ulcers, or infections in the legs or feet,
- irregular heartbeats,
- loss of movement,
- stomach pain,
- unusual drowsiness, and
Rare side effects of Canagliflozin include:
This is not a complete list of side effects and other serious side effects or health problems may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.
What Other Drugs Interact with Canagliflozin?
If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.
- Canagliflozin has severe interactions with no other drugs.
- Canagliflozin has serious interactions with no other drugs.
- Canagliflozin has moderate interactions with at least 70 other drugs.
- Canagliflozin has minor interactions with no other drugs.
This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this drug, tell your doctor or pharmacist of all the drugs you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.
What Are Warnings and Precautions for Canagliflozin?
Effects of drug abuse
- See “What Are Side Effects Associated with Using Canagliflozin?”
- See “What Are Side Effects Associated with Using Canagliflozin?”
- Causes intravascular volume contraction and symptomatic hypotension and/or acute kidney injury can occur, particularly if eGFR less than 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) (e.g., ACE inhibitors, ARBs); monitor for signs and symptoms during therapy
- Increases in serum creatinine and decreases in estimated GFR also observed with initiation
- 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
- Necrotizing fasciitis of the perineum (Fournier gangrene) reported with SGLT2 inhibitors; signs and symptoms include tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, and have a fever over 100.4ºF or a general feeling of being unwell; if suspected, discontinue SGLT2 inhibitor and start treatment immediately with broad-spectrum antibiotics and surgical debridement if necessary
- Genital mycotic infections may occur, patients with history of genital mycotic infections and uncircumcised males are more susceptible
- Increased risk of bone fracture, occurring as early as 12 weeks after treatment initiation, reported; consider factors that contribute to fracture risk before initiating therapy
- Hypersensitivity reactions, including angioedema and anaphylaxis reported; reactions generally occurred within hours to days after initiation; if hypersensitivity reactions occur, discontinue therapy; treat and monitor until signs and symptoms resolve
- Lower limb amputation
- 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 for infection, new pain or tenderness, and sores or ulcers involving the lower limbs; discontinue if these complications occur
- Ketoacidosis associated with SGLT2 inhibitors reported; monitor for signs and symptoms of ketoacidosis (e.g., difficulty breathing, nausea, vomiting, abdominal pain, confusion, unusual fatigue or sleepiness)
- Before initiating therapy, consider factors in patient history that may predispose to ketoacidosis, including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse
- Consider temporarily discontinuing canagliflozin for at least 3 days before undergoing scheduled surgery to avoid euglycemic ketoacidosis
- Consider monitoring for ketoacidosis and temporarily discontinuing therapy in other clinical situations known to predispose to ketoacidosis (e.g., prolonged fasting due to acute illness or post-surgery)
- Restart once the patient’s oral intake is back to baseline and any other risk factors for ketoacidosis (blood acid buildup) are resolved
- Drug interaction overview
- Major substrate of UGT1A9 and UGT2B4; weak inhibitor of P-gp
- Coadministration of canagliflozin with rifampin, a nonselective inducer of several UGT enzymes, including UGT1A9, UGT2B4, decreased canagliflozin AUC by 51%
- Hypoglycemia risk increased with insulin and insulin secretagogues, consider a lower dose of insulin or the insulin secretagogue
- An increase in AUC and mean peak drug concentration of digoxin (a P-gp substrate) was observed when coadministered with canagliflozin 300 mg; monitor
- Laboratory testing
- Urine glucose tests is not recommended in patients taking SGLT2 inhibitors as SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests; use alternative methods to monitor glycemic control
- 1,5-AG assay is not recommended as measurements of 1,5- AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors; use alternative methods to monitor glycemic control
Pregnancy and Lactation
- Based on animal data showing adverse renal effects, not recommended during the second and third trimesters of pregnancy
- Data are limited in pregnant women and are not sufficient to determine a drug associated risk for major birth defects or miscarriage
- Clinical considerations
- Poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, stillbirth, and delivery complications
- Poorly controlled diabetes increases fetal risk for major birth defects, stillbirth, and macrosomia related morbidity
- No information regarding distribution in human milk or effects on the breastfed infant or milk production
- Present in milk of lactating rats
- Since human kidney maturation occurs in utero and during the first 2 years of life when lactational exposure may occur, there may be risk to the developing human kidney
- Inform women not to breastfeed while taking canagliflozin