Invokana, the brand name for Canagliflozin is a medicine used in the treatment of type 2 diabetes. Oral administration of the medicine along with definite diet and exercise lifestyles pave the way for best results in patients looking to extract its full functionality. Used extensively in the USA and in the UK, the popularity of this medicinal drug in the treatment, maintenance and cure of type 2 diabetes has been stated as an effective practice that leads to sustainable physiological improvement. Like every other drug, Invokana too comes with its own set of boundaries in terms of side effects and long-term consequences, but its significance as one of most widely prescribed medicine for type 2 diabetes control is considered for its intrinsic properties.

Prescription Name and Overview

Canagliflozin, an inhibitor for sodium-glucose cotransporter 2 that is instrumental in reabsorbing the filtered glucose by the kidney, is sold under the following prescription drug names:

• Invokana
• Sulisent
• Prominad

Invokana is used in tabular forms and administered orally. Each tablet contains between 102 to 306 mg of Canagliflozin, the active ingredient used in the treatment for type 2 diabetes. Clinical studies show that Canagliflozin has an impactful positive effect on controlling glycemic levels but its significance also involves the protection and control of cardiovascular discrepancies in diabetic patients, substantially reducing risks of heart failures and heart attacks. However, like any other medication, Invokana too has its placebo-controlled effects on patients that have been studied and passed as an effective treatment. Its reactive progression with other physiological features and organs has shown a limitless list of effective progress.

Generic Name and Overview

The active ingredient in Invokana is Canagliflozin that works through the physiological mechanism of reducing blood sugar level in patients with type 2 diabetes. In medicinal definitions of classification, it falls in a class namely sodium-glucose cotransporter 2 inhibitors or SGLT2. Without any external impetus, glucose gets filtered in the bloodstream and into the kidneys for absorption and production of urine in a bidirectional way. SGLT2 is an enzyme that helps in reabsorbing glucose from urine so that no nutrients are lost through excretion. Canagliflozin helps in blocking this enzymatic action of SGLT2, thus reducing the reabsorption of glucose from urine. As a result, diabetic patients with excess glucose in their bloodstream get benefitted by the drug as excess glucose in the bloodstream is lost through excretion.

OTC Name and Overview

The OTC or prescription name for Canagliflozin is Invokana. However, other OTC names include Sulisent and Prominad.

            Manufacturer

The approval of Invokana as a prescription drug was approved by the U.S. Food and Drug Administration (FDA) as a treatment in patients with type 2 diabetes in March 2013. Manufactured and circulated by Janssen Pharmaceuticals Inc., Invokana is the only oral medication that offers substantial glycemic control along with other positive physiological effects. Originally developed and marketed by Mitsubishi Tanabe Pharma, Invokana is sold under the license of Janssen. Working with various brands of Johnson & Johnson, Janssen looks forward in promoting the availability of the medicine extensively across the country.

            Labeled Indications

The labeled indications for Invokana (Canagliflozin) are as follow:

• Patients suffering from type 2 diabetes mellitus taking Invokana in combination with a healthy diet and exercise can significantly reduce blood sugar levels if followed with regularity
• Clinical studies have shown that Invokana is responsible for reducing the risk of any adverse cardiovascular discrepancies including myocardial infarction, nonfatal stroke, heart failures in adults diagnosed with type 2 diabetes and CVD or cardiovascular disease.

There is a limitation of use for Invokana and it is not a recommended medicinal drug for patients diagnosed with type 1 diabetes or in a case of diabetic ketoacidosis. Patients with severe renal impairment or those who are on regular dialysis are also not recommended to use Invokana as a medicinal treatment. Invokana’s effects and safety in children under the age of 18 are still not known.

General dosage recommends the patient to take one pill of Invokana right before the first meal of the day. Usually, the starting dose is at 100 mg that is taken in tabular form once daily and the maximum dose is measured at 300 mg that is taken tabular form once daily. The dosage should be monitored based on the clarity of renal functionalities as well as regular assessment to scrutinize the effects of Canagliflozin in an individual.

            Active Ingredients

Invokana contains Canagliflozin as its active ingredient which is a sodium glucose co-transporter 2 (SGLT2) inhibitor, the enzymatic transporter that absorbs glucose from urine before it is excreted. The active ingredient of Invokana, Canagliflozin is chemically known as (1S)-1,5-anhydro-1-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-D-glucitol hemihydrate and its molecular formula and weight are C24H25FO5S•½ H2O and 453.53, respectively. Canagliflozin is insoluble in solvents between the pH ranges of 1.1 to 12.9.

The inactive ingredients in Invokana tablet include croscarmellose sodium, hydroxypropyl cellulose, lactose anhydrous, magnesium stearate, and microcrystalline cellulose. The outer coating of commercially available tablets consists of polyvinyl alcohol (partially hydrolyzed), titanium dioxide, macrogol/PEG, talc, and iron oxide yellow.

What Is It Used For?

Canagliflozin, the active ingredient in Invokana is an anti-diabetic drug that is administered for glycemic control in patients with type 2 diabetes. It has also shown to reduce cardiac complications like heart attacks, myocardial infarction in patients who have a diversion towards such cardiovascular problems. Used as an adjunct to good dietary practices and mild exercise, its dosage is fixed by the medical practitioner depending on the individual requirements of the patient.

       How Does it Work?

An inhibitor of SGLT2 or subtype 2 sodium-glucose transport proteins is instrumental in roughly 90% renal glucose reabsorption. Canagliflozin works as a blocker of SGLT2’s enzymatic properties that helps in up to 119 grams of blood glucose to get excreted through urine per day. 119 grams of glucose is equivalent to 476 kilocalories, a quantitative measure which if eliminated from the body every day substantially controls blood sugar levels. Moreover, due to the elimination of water through osmotic dieresis, the chances of developing blood pressure also get reduced. On the other hand, this mechanism may be associated with hypoglycemia or low blood sugar level at an alarming rate as opposed to the effects of other anti-diabetic drugs like insulin or sulfonylurea derivates.

       What are the Approved Uses?

The approved uses of Invokana include:

• Patients suffering from type 2 diabetes mellitus taking Invokana in combination with a healthy diet and exercise can significantly reduce blood sugar levels if followed with regularity
• Clinical studies have shown that Invokana is responsible for reducing the risk of any adverse cardiovascular discrepancies including myocardial infarction, nonfatal stroke, heart failures in adults diagnosed with type 2 diabetes and CVD or cardiovascular disease.

It is best recommended for patients with or without any medical history to consult a medical practitioner and extensively discuss any danger or adverse side effects from using the drug.

       Production Anecdotes / History

Canagliflozin, the active ingredient in Invokana is an anti-diabetic drug that is administered for glycemic control in patients with type 2 diabetes. It has also shown to reduce cardiac complications like heart attacks, myocardial infarction in patients who have a diversion towards such cardiovascular problems. Used as an adjunct to good dietary practices and mild exercise, its dosage is fixed by the medical practitioner depending on the individual requirements of the patient.

Precautions

• Lower Limb Amputation
• Hypotension
• Ketoacidosis
• Acute Kidney Injury
• Urosepsis And Pyelonephritis
• Hypoglycemia With Concomitant Use With Insulin And Insulin Secretagogues
• Necrotizing Fasciitis Of The Perineum
• Genital Mycotic Infections
• Hypersensitivity Reactions
• Bone Fracture
• Increase In Low-Density Lipoprotein

Like every other drug, Invokana comes with its sets of precautionary measures. Consult your doctor and go through an extensive medical inspection before the use of the drug is prescribed.

Long-term Use Considerations

Clinical studies have proposed that the drug might be responsible for the fall of estimated glomerular filtration rate that measures the functional assertion of the kidney. This indicates that patients who take Invokana may run the risk of damaging their kidney in terms of its functional fluency.

Although Invokana is approved by the FDA, it is still under scrutiny whether the drug can cause permanent damage to the kidney that might lead to adverse damages or nephropathy.

Invokana’s effects on cardiovascular conditions are also an area of medical questionability. In clinical trials, it has been proved that almost everyone taking the test has experienced some kind of cardiovascular event including non-fatal stroke and heart attacks which eventually balanced out after a month of regular trial proceedings.

However, these extensive tests and trials do not hold the accuracy to predict its long-term effects.

Drug Interactions

Invokana may increase the risk of extreme dehydration if combined with diuretic drugs.

    Can Interact with the Following

• Interaction of Canagliflozin can be stimulated with any of the following:
• aliskiren
• alpha agonists (e.g., clonidine, methyldopa)
• angiotensin-converting enzyme inhibitors (ACEIs; captopril, enalapril, ramipril)
• angiotensin receptor blockers (ARBs; e.g., candasartan, irbesartan, losartan)
• aripiprazole
• barbiturates (e.g., butalbital, pentobarbital, phenobarbital)
• beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol)
• buserelin
• calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
• carbamazepine
• danazol
• digoxin
• diuretics (water pills; e.g., furosemide, hydrochlorothiazide, triamterene)
• diabetes medications (e.g., chlorpropamide, glipizide, glyburide, insulin, metformin, nateglinide, rosiglitazone)
• dofetilide
• efavirenz
• eplerenone
• estrogens
• garlic
• ginseng
• goserelin
• heparin
• inhaled corticosteroids (e.g., budesonide, ciclesonide, fluticasone)
• leuprolide
• low-molecular-weight heparins (e.g., dalteparin, enoxaparin, tinzaparin)
• monoamine oxidase inhibitors (MAOIs; e.g., moclobemide, phenelzine, rasagiline, selegiline, tranylcypromine)
• nandrolone
• octreotide
• oral corticosteroids (e.g., dexamethasone, hydrocortisone, prednisone)
• pegvisomant
• phenytoin
• pimozide
• primidone
• quinolone antibiotics (e.g., ciprofloxacin, norfloxacin, ofloxacin)
• rifampin
• ritonavir
• St. John’s Wort
• selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine, paroxetine, sertraline)
• somatotropin
• testosterone

       Can’t Interact with the Following

No studies have been concluded on this.

When To Stop Taking

Stop the oral administration of Invokana if you develop any of the following if any allergic reaction is instigated. Such reactions may include the following:

• Rashes
• Kidney problems or complications
• Hives or raised red patches on the skin
• Difficulty in breathing
• Swelling of tongue, throat, face or lips

Long-Term Side Effects

There are many important long-term side effects associated with the use of Invokana.

• Amputations- Invokana increases the risk of amputations along the lower limb. This might include the removal of part of the foot or toe, leg or above the knee. Some extreme cases also call for amputation in both limbs. This risk is increased manifold due to a number of factors like history of amputation, heart diseases, narrow blood vessels in legs, damaged nerves, diabetic foot sores or ulcers
• Dehydration is another long-term side effect that might cause permanent kidney problems, especially in patients above the age of 65
• Another common side effect that develops in patients taking Invokana is a vaginal yeast infection in females and balanitis or yeast infection of the penis in males
• Ketoacidosis or extremely low blood sugar level in patients who take Invokana might lead to death
• Urinary tract infection is another adverse side effect of Invokana use
• Patients taking Invokana run the risk of developing brittle bones which results in frequent bone fractures

FDA Warnings (History Of)

The approval of Invokana as a prescription drug was approved by the U.S. Food and Drug Administration (FDA) as a treatment in patients with type 2 diabetes in March 2013. Manufactured and circulated by Janssen Pharmaceuticals Inc., Invokana is the only oral medication that offers substantial glycemic control along with other positive physiological effects. Although Invokana is approved by the FDA, it is still under scrutiny whether the drug can cause permanent damage to the kidney that might lead to adverse damages or nephropathy. Invokana’s effects on cardiovascular conditions are also an area of medical questionability. In clinical trials, it has been proved that almost everyone taking the test has experienced some kind of cardiovascular event including non-fatal stroke and heart attacks which eventually balanced out after a month of regular trial proceedings.

Other Common Side Effects

• headache
• drowsiness
• weakness
• dizziness
• confusion
• irritability
• hunger
• fast heart-beat
• sweating
• shaking or feeling jittery
• change in urine frequency

Lawsuits

As per clinical tests, the effects of Invokana produce ample proof about the fatal and non-fatal consequences of its use. There have been reports of amputation, kidney complications, ketoacidosis, and other medical issues that have led the FDA to release a black box warning against the drug. Some patients have suffered its side effects so adverse that it led to permanent disability. As a result of such consequential syndromes, many patients and their families have gone forward with legal actions against the manufacturers of Invokana, Janssen Pharmaceuticals and Johnson and Johnson. However, the eradication of these risks and warning warrants will receive more clarity upon further experiments and investigations.

Tracy Everhart

Tracy Everhart is the Editor for Drug Law Journal. A highly-trained and certified medical professional, Tracy is also an accomplished medical writer. After spending years on the front lines of the medical profession, Tracy now devotes her expertise and skills to researching and reporting on new drugs and devices that enter the market, as well as their side-effects and the real-life stories involved. Prior to joining Drug Law Journal, Tracy wrote for benchmark online healthcare resources focused on families and, in particular, women’s health issues. Tracy holds post-graduate degrees from both the American College of Healthcare Sciences and the Yale School of Nursing. She is also a graduate of both Hampshire College, where she studied microbiology and the University of South Carolina school of nursing.