canagliflozin


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canagliflozin

(kan-a-gli-floe-zin ) ,

Invokana

(trade name)

Classification

Therapeutic: antidiabetics
Pharmacologic: sodium glucose co transporter 2 sglt2 inhibitors
Pregnancy Category: C

Indications

Adjunct to diet and exercise in the management of type 2 diabetes mellitusMay be used with other antidiabetic agents.

Action

Inhibits proximal renal tubular sodium-glucose co-transporter 2 (SGLT2), which determines reabsorption of glucose from the tubular lumen. Inhibits reabsorption of glucose, lowers renal threshold for glucose, and increases excretion of glucose in urine.

Therapeutic effects

Improved glycemic control

Pharmacokinetics

Absorption: Well absorbed (65%) following oral administration
Distribution: Extensive tissue distribution
Protein Binding: 99%
Metabolism and Excretion: Mostly metabolized by UDP-glucuronyl transferases (UGT) to inactive metabolites, minimal metabolism by CYP3A4 (7%). 50% excreted in feces as parent drug and metabolites, 33% as metabolites in urine, <1% excreted in urine as unchanged drug.
Half-life: 10.6 hr

Time/action profile (effects on HbA1C)

ROUTEONSETPEAKDURATION
POunknownunknown24 hr

Contraindications/Precautions

Contraindicated in: HypersensitivitySevere renal impairment (eGFR <45 mL/min/1.73 m2), end-stage renal disease or on dialysis;Severe hepatic impairment; Lactation: Avoid use, discontinue breast feeding or discontinue canagliflozin.
Use Cautiously in: eGFR <60 mL/min/1.73 m2 (monitor frequently), ↑ risk of adverse reactions related to ↓ intravascular volume; Geriatric: ↑ risk of adverse reactions related to ↓ intravascular volume;Hypotension (correct prior to treatment, especially if eGFR 30–60 mL/min, age >75 yr, or concurrent use of loop diuretics, ACE inhibitors, or ARBs; Obstetric: Use during pregnancy only if potential maternal benefit justifies potential fetal risk; Pediatric: Safe and effective use in children <18 yr has not been established.

Adverse Reactions/Side Effects

Cardiovascular

  • hypotension

Gastrointestinal

  • abdominal pain
  • constipation
  • nausea

Genitourinary

  • female mycotic infections (most frequent)
  • glucosuria
  • male mycotic infections
  • ↓ renal function
  • urinary tract infection
  • ↑ urination
  • vulvovaginal pruritus

Endocrinologic

  • hypoglycemia (with other medications) (life-threatening)

Fluid and Electrolyte

  • hyperkalemia (most frequent)
  • hypermagnesemia
  • hyperphosphatemia
  • thirst

Metabolic

  • hyperlipidemia

Miscellaneous

  • hypersensitivity reactions, including generalized urticaria

Interactions

Drug-Drug interaction

Blood levels are ↓ by UGT inducers including phenobarbital, phenytoin, rifampin, and ritonavir ; ↑dose may be required.↑ risk of hypoglycemia with insulin or insulin secretagogues, dose adjustments may be required.May↑ blood levels and effects of digoxin ; levels should be monitored.↑ risk of hyperkalemia with potassium-sparing diuretics or medications that interfere with the renin-angiotnesin-aldosterone system.

Route/Dosage

Oral (Adults) eGFR ≥ 60 mL/min/1.73 m2—100 mg once daily initially, may be increased to 300 mg once daily; Concurrent use of UGT inducers (phenobarbital, phenytoin, rifampin, ritonavir)—if maintenance dose is 100 mg daily, may require increase to 300 mg daily.

Renal Impairment

Oral (Adults) eGFR 45–60 mL/min/1.73 m2100 mg once daily

Availability

Tablets: 100 mg, 300 mg

Nursing implications

Nursing assessment

  • Observe patient for signs and symptoms of hypoglycemic reactions (abdominal pain, sweating, hunger, weakness, dizziness, headache, tremor, tachycardia, anxiety)
  • Monitor for signs and symptoms of volume depletion (dizziness, feeling faint, weakness, orthostatic hypotension) after initiating therapy.
  • Lab Test Considerations: Monitor hemoglobin A1C prior to and periodically during therapy
    • May cause ↑ uric acid levels
    • May ↑serum creatinine and ↓eGFR. Monitor renal function, especially in patients with eGFR <60 mL/min/1.73 m2
    • May cause ↑ serum potassium, magnesium, and phosphate levels. Monitor electrolytes periodically during therapy.
    • May cause ↑ LDL-C. Monitor serum lipid levels periodically during therapy.

Potential Nursing Diagnoses

Imbalanced nutrition: more than body requirements (Indications)
Noncompliance (Patient/Family Teaching)

Implementation

  • Patients stabilized on a diabetic regimen who are exposed to stress, fever, trauma, infection, or surgery may require administration of insulin
  • Correct volume depletion prior to beginning therapy with canagliflozin.
  • Oral: Administer before the first meal of the day.

Patient/Family Teaching

  • Instruct patient to take canagliflozin as directed. Take missed doses as soon as remembered, unless it is almost time for next dose; do not double doses. Advise patient to read the Medication Guide before starting and with each Rx refill; new information may be available
  • Explain to patient that canagliflozin helps control hyperglycemia but does not cure diabetes. Therapy is usually long term
  • Instruct patient not to share this medication with others, even if they have the same symptoms; it may harm them
  • Encourage patient to follow prescribed diet, medication, and exercise regimen to prevent hyperglycemic or hypoglycemic episodes
  • Review signs of hypoglycemia and hyperglycemia with patient. If hypoglycemia occurs, advise patient to take a glass of orange juice or 2–3 tsp of sugar, honey, or corn syrup dissolved in water, and notify health care professional
  • Instruct patient in proper testing of blood glucose and urine ketones. Inform patient that canagliflozin will cause a positive test result when testing for urine glucose. These tests should be monitored closely during periods of stress or illness and health care professional notified if significant changes occur
  • Inform patient that canagliflozin may cause yeast infections. Women may have signs and symptoms of a vaginal yeast infection (vaginal odor, white or yellow vaginal discharge [may be lumpy or look like cottage cheese], vaginal itching). Men may have signs and symptoms of a yeast infection of the penis (redness, itching, or swelling of penis; rash on penis; foul smelling discharge from penis; pain in skin around penis). Advise patient to notify health care professional if yeast infection occurs.
  • Advise patient to notify health care professional promptly if rash; hives; or swelling of face, lips, or throat occur
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially other oral hypoglycemic medications
  • Advise patient to notify health care professional if pregnancy is planned or suspected or if breast feeding

Evaluation/Desired Outcomes

  • Improved hemoglobin A1C and glycemic control in adults with Type II diabetes.
References in periodicals archive ?
Rates of heart failure varied according to baseline characteristics, such as age, renal function and other disease history characteristics, but effects of canagliflozin on risk of CV death or HHF were mostly comparable across numerous subgroups.
Effect of canagliflozin on serum uric acid in patients with type 2 diabetes mellitus.
FDA Drug Safety Communication: FDA confirms increased risk of leg and foot amputations with the diabetes medicine canagliflozin (Invokana.
9 events per 1,000 person-years of canagliflozin treatment and 31.
Empagliflozin and canagliflozin have been shown to have beneficial effects on preservation of renal function in patients with diabetic kidney disease who are at risk for cardiovascular events.
The Food and Drug Administration has added a boxed warning to the label of diabetes drug canagliflozin for the risk of lower limb amputation.
4 million diabetic patients show that canagliflozin in the US, and dapagliflozin in Europe (and Asia) also reduce death rates among diabetic patients with heart disease and even among those with no established heart disease.
The medication, a once-daily fixed-dose combination therapy of canagliflozin and metformin hydrochloride extended release, is to be used to improve blood glucose control when treatment with two medications is appropriate.
Canagliflozin (Invokana) and dapaglifrozin (Farxiga) were approved by the FDA.
We are reporting a timely case of atypical euglycemic diabetic ketoacidosis in a type 1 diabetic patient treated with sodium-glucose cotransporter-2 (SGLT-2) inhibitor canagliflozin.
SGLT-2 inhibitors Canagliflozin Causes excess glucose (Invokana[R]) to be excreted in the Dapagliflozin urine.
Other options for weight-neutral treatment of T2DM include exenatide, which also is available as a once weekly injectable formulation, canagliflozin, and the gliptins (sitagliptin, saxagliptin, and linagliptin) (Table 4).