INVOKANA (canagliflozin)

There are 1 contraindications. Absolute contraindication.

Contraindication List
History of diabetes-related lower-extremity amputation

There are 12 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
Diabetic foot infection
Hyperkalemia
Hypoglycemic disorder
Hypovolemia
Invasive surgical procedure
Necrotizing fasciitis of perineum or genital area
Peripheral vascular disease
Pregnancy

There are 2 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Diabetic peripheral neuropathy
Osteopenia

There are 24 severe adverse reactions.

More Frequent	Less Frequent
Hypoglycemic disorder	Dehydration Hypermagnesemia Hypersensitivity drug reaction Hypotension Syncope

Rare/Very Rare
Accidental fall Acute kidney injury Anaphylaxis Angioedema Bacterial sepsis Depression Diabetic ketoacidosis Fracture Hyperkalemia Ketoacidosis Kidney disease with reduction in glomerular filtration rate (GFr) Metabolic acidosis Necrotizing fasciitis of perineum or genital area Osteopenia Pancreatitis Pyelonephritis Renal cell carcinoma Urosepsis

There are 20 less severe adverse reactions.

More Frequent	Less Frequent
Increased urinary frequency Urinary tract infection Vulvovaginal candidiasis	Candidal balanitis Constipation Dental abscess Fatigue General weakness Genital organ pruritus Hypercholesterolemia Hyperlipidemia Hyperphosphatemia Increased hemoglobin Nausea Orthostatic hypotension Polydipsia Xerostomia

Rare/Very Rare
Acute abdominal pain Skin photosensitivity Urticaria

There is insufficient evidence with canagliflozin in pregnant women to evaluate a drug-associated risk for major birth defects or miscarriage. Based on the results of reproductive and developmental toxicity studies in animals, canagliflozin use during pregnancy may affect renal development and maturation, especially during the second and third trimesters of pregnancy. In juvenile animal studies, adverse renal pelvic and tubule dilatations that were not reversible were observed in rats when canagliflozin was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy, at an exposure 0.5

times the 300-mg clinical dosage, based on area under the concentration-time curve (AUC). Poorly controlled diabetes mellitus during pregnancy carries risks to the mother and fetus, including DKA, pre-eclampsia, spontaneous abortions, preterm delivery, delivery complications, major birth defects, stillbirth, and macrosomia-related morbidity. The manufacturer states that canagliflozin therapy is not recommended in pregnant women during the second and third trimesters of pregnancy.

There is no information regarding the presence of canagliflozin in human milk, the effects on the breast-fed infant, or the effects on milk production. Canagliflozin is distributed into milk in rats. Juvenile rats directly exposed to canagliflozin showed a risk to the developing kidney (renal pelvic and tubular dilatations) during maturation.

Since human kidney maturation occurs in utero and during the first 2 years of life when lactational exposure may occur, there may be a risk to the developing human kidney. Because of the potential for serious adverse reactions in nursing infants from canagliflozin, use of the drug is not recommended while breastfeeding.

Among patients in 13 clinical trials, 2294 were 65 years of age or older and 351 were 75 years of age or older, including one trial in patients 55 to 80 years of age. Geriatric patients experienced reduced efficacy of canagliflozin compared with younger patients as evidenced by smaller reductions in glycosylated hemoglobin (hemoglobin A1c; HbA1c). Patients 65 years of age and older were more likely to experience certain adverse effects related to reduced intravascular volume (e.g., hypotension, postural dizziness, orthostatic hypotension, syncope, dehydration) with canagliflozin, particularly those receiving 300 mg daily; a prominent increase in the incidence of volume depletion-related adverse effects in these trials was seen in patients who were 75 years of age and older.