INVOKAMET (Canagliflozin/Metformin)

What is this medication? 

INVOKAMET (Canagliflozin/Metformin)
Antidiabetic Agents; Biguanide; Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor

INVOKAMET (Canagliflozin/Metformin) is indicated for the treatment of Diabetes mellitus type 2.

ALERT: WARNING
Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL.

Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (eg, carbonic anhydrase inhibitors such as topiramate), ≥65 years, having a radiological study with contrast, surgery and other procedures, hypoxic states (eg, acute congestive heart failure), excessive alcohol intake, and hepatic impairment.

Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the full prescribing information.

If metformin-associated lactic acidosis is suspected, immediately discontinue empagliflozin/metformin and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

How does this medication work? 

SGLT2 is in the proximal renal tubules of the nephron (a functional unit of the kidney) and is the main site of reabsorption of filtered glucose.  Canagliflozin inhibits this transporter which lowers glucose reabsorption and lowers the renal threshold for glucose resulting in its urinary excretion thereby lowering plasma glucose concentrations.

Metformin is believed to exhibit multiple mechanisms of action which ultimately decreases gluconeogenesis (hepatic glucose production) in the liver, decreases intestinal absorption of glucose and improves the insulin sensitivity of muscle which increases peripheral glucose uptake and overall utilization.  Metformin also exhibits an anti-androgenic effect in women with insulin resistance.

How should I take this medication? 

Oral:
Initial: Individualize initial dose based on patient’s current antidiabetic regimen. May gradually increase dose based on effectiveness and tolerability to a maximum of Canagliflozin 300mg/Metformin 2000mg per day.

How to Take: Follow instructions provided by physician/pharmacy label, take consistently at same times each day unless otherwise directed.  Monitor blood pressure when initiating due to diuretic effect. Administer IR tablets twice daily with meals or extended-release tablets once daily with breakfast. ER tablets should not be split, crushed, chewed, or dissolved.

You Need to Avoid: Do not skip standard diabetic foot care regimen.  Must monitor for wounds or signs of new infection, ulcers, sores or new pain or tenderness.  A trial showed a higher frequency of lower limb amputations compared to placebo so caution must be taken.  Avoid volume depletion or dehydration due to diuretic effect of this medication. Alcohol should be avoided due to increased risk of lactic acidosis from metformin use.

What should I watch for while using this medication? 

Before starting INVOKAMET (Canagliflozin/Metformin), make sure your physician is aware of any allergies, medications you currently take, if you have kidney disease, liver disease, heart failure, a history of diabetic ketoacidosis, have had bariatric surgery, are pregnant or breastfeeding.  INVOKAMET (Canagliflozin/Metformin) has been associated with rare but serious adverse reactions such as increased risk of bone fracture, genital mycotic infections, hypersensitivity reaction, hypotension, hyperkalemia, ketoacidosis, lactic acidosis, necrotizing fasciitis, increased risk of lower limb amputation, acute kidney injury, urinary tract infections, and vitamin B12 deficiency. 

What if I miss a dose?

If you miss a dose of medication, try to take it as soon as possible. However, if it is almost time for your next dose, take only that scheduled dose. Do not take double or extra doses.

How should I store this medication?

Keep out of the reach of children at all times. Store at room temperature, 59 to 86° F (15 to 30° C). Protect from light. Keep the container tightly closed. Properly dispose of any unused medication after the expiration date.

What are the possible side effects of using this medication? 

Urinary tract infection, increased urine output, genitourinary fungal infection, nausea, thirst, hypotension, diarrhea, nausea, vomiting, flatulence, infection.

Note this is not a complete list of side effects for INVOKAMET (Canagliflozin/Metformin), only common ones.