Canagliflozin (Invokana), the first drug in a new class called sodium-glucose cotransporter 2 inhibitors, was recently approved to treat type 2 diabetes. Canagliflozin prevents the reabsorption of glucose in the kidneys and lowers the renal threshold for glucose; these two actions are responsible for lowering the circulating level of glucose. When administered before a meal, the drug delays intestinal glucose absorption and reduces postprandial glucose levels.

Fasting blood glucose and glycated hemoglobin (HbA1c) levels are used to determine short- and long-term glycemic control. Because canagliflozin speeds up glucose excretion, urine specimens will test positive for glucose, which isn't to be misinterpreted as an indication that the circulating level of glucose is especially high. Canagliflozin cannot be used to treat type 1 diabetes or diabetic ketoacidosis.

The Food and Drug Administration (FDA) approval was based on nine clinical trials involving more than 10,000 patients with type 2 diabetes. Canagliflozin was studied as monotherapy and as part of a treatment regimen with other type 2 diabetes therapies, including metformin, sulfonylurea, pioglitazone, and insulin.

Canagliflozin's label carries several warnings. First, the loss of glucose through urine promotes diuresis, and patients may develop hypovolemia and hypotension; as a result, patients should be assessed for fluid-volume deficits. Hypovolemia should be corrected before drug therapy begins if the patient has renal impairment, is an older adult, is hypotensive, or is taking a diuretic. Another warning notes that canagliflozin can impair renal function. Patients with a history of renal impairment need to be monitored. Patients with severe renal impairment or end-stage renal disease and patients on dialysis shouldn't take canagliflozin. Patients with renal impairment should also be monitored for hyperkalemia. The use of insulin and insulin secretagogues (such as sulfonylureas) can lead to hypoglycemia, and that risk is heightened with concomitant canagliflozin use; lower dosages of the insulin and insulin secretagogue may be necessary. Another warning on the canagliflozin label is that patients can experience an elevated low-density lipoprotein (LDL) cholesterol level during canagliflozin therapy and should be monitored for it. Genital mycotic infections (vaginal or penile yeast infections) and hypersensitivity reactions are also possible. Because the drug hasn't been studied in patients with severe liver disease, its use isn't recommended in these patients.

The most common adverse effects are vaginal yeast infections, urinary tract infections, and increased urination. Older adults and patients with renal impairment are more likely to experience adverse reactions. Increases in serum potassium, magnesium, and phosphate levels are possible, as are increases in hemoglobin levels. Hypotension, especially orthostatic hypotension, is possible because of the drug's diuretic effect, especially in patients who have volume depletion before the start of therapy.

In light of these adverse effects and those associated with other antidiabetic drugs-and in concordance with federal requirements regarding drug safety in pediatric populations-the FDA has required the manufacturer of canagliflozin to conduct five postmarketing studies: "a cardiovascular outcomes trial; an enhanced pharmacovigilance program to monitor for malignancies, serious cases of pancreatitis, severe hypersensitivity reactions, photosensitivity reactions, liver abnormalities, and adverse pregnancy outcomes; a bone safety study; and two pediatric studies under the Pediatric Research Equity Act (PREA), including a pharmacokinetic and pharmacodynamic study and a safety and efficacy study."

There are a few significant interactions between canagliflozin and other drugs, and nurses should determine what other drug therapy patients are currently undergoing when they're about to start treatment with canagliflozin. When coadministered with canagliflozin, rifampin, phenytoin, phenobarbital, and ritonavir can decrease the circulating level of canagliflozin; higher doses of canagliflozin may be required. Coadministration with digoxin can increase circulating levels of digoxin; nurses should monitor the digoxin level carefully in patients taking both medications.

Education should focus on the care and assessments required both to monitor the patient for adverse effects and to prevent their occurrence. To prevent hypovolemia, hypotension, and urinary tract infections, patients should be instructed to drink plenty of fluids and remain hydrated. Patients should change positions slowly to prevent sudden orthostatic changes in blood pressure. They should be aware that more frequent urination will occur as a normal part of canagliflozin therapy. Patients will need to return for periodic blood work to assess kidney function, potassium and other electrolyte levels, and the LDL cholesterol level, as well as for assessment of glucose control (HbA1c and fasting blood glucose testing). Nurses should explain the signs and symptoms of allergic reactions and yeast infections and instruct patients to contact their prescriber if they arise.

Full prescribing information on canagliflozin is available at http://1.usa.gov/15ei66S.