Vokanamet (Canagliflozin_Metformin hydrochloride)

Vokanamet (Canagliflozin_Metformin hydrochloride) Uses, Dosage, Side Effects, Food Interaction and all others data.

Canagliflozin is a Sodium-glucose co-transporter 2 (SGLT2) inhibitor. Sodium-glucose co-transporter 2 (SGLT2) expressed in the proximal renal tubules, is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen. By inhibiting SGLT2, Canagliflozin reduces reabsorption of filtered glucose and lowers the renal threshold for glucose (RTG), and thereby increases urinary glucose excretion.

This drug increases urinary glucose excretion and decreases the renal threshold for glucose (RTG) in a dose-dependent manner . The renal threshold is defined as the lowest level of blood glucose associated with the appearance of detectable glucose in the urine . The end result of canagliflozin administration is increased urinary excretion of glucose and less renal absorption of glucose, decreasing glucose concentration in the blood and improving glycemic control.

A note on type 2 diabetes and cardiovascular disease

The risk of cardiovascular events in diabetes type 2 is increased due to the damaging effects of diabetes on blood vessels and nerves in the cardiovascular system. In particular, there is a tendency for hyperglycemia to create pro-atherogenic (plaque forming) lesions in blood vessels, leading to various fatal and non-fatal events including stroke and myocardial infarction . Long-term glycemic control has been proven to be effective in the prevention of cardiovascular events such as myocardial infarction and stroke in patients with type 2 diabetes .

Trade Name Vokanamet (Canagliflozin_Metformin hydrochloride)
Generic Canagliflozin + Metformin Hydrochloride
Type
Therapeutic Class
Manufacturer
Available Country Austria, Belgium, Bulgaria, Croatia (Hrvatska), Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Liechtenstein, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, United Kingdom
Last Updated: September 19, 2023 at 7:00 am
Vokanamet (Canagliflozin_Metformin hydrochloride)
Vokanamet (Canagliflozin_Metformin hydrochloride)

Uses

Canagliflozin is used for an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.

Vokanamet (Canagliflozin_Metformin hydrochloride) is also used to associated treatment for these conditions: Cardiovascular Events, Cardiovascular Mortality, End Stage Renal Disease (ESRD), Type 2 Diabetes Mellitus, Hospitalization due to cardiac failure, Increased serum creatinine, Glycemic Control

How Vokanamet (Canagliflozin_Metformin hydrochloride) works

The sodium-glucose co-transporter2 (SGLT2), is found in the proximal tubules of the kidney, and reabsorbs filtered glucose from the renal tubular lumen. Canagliflozin inhibits the SGLT2 co-transporter. This inhibition leads to lower reabsorption of filtered glucose into the body and decreases the renal threshold for glucose (RTG), leading to increased glucose excretion in the urine .

Dosage

Vokanamet (Canagliflozin_Metformin hydrochloride) dosage

The recommended starting dose of Canagliflozin is 100 mg once daily, taken before the first meal of the day. Dose can be increased to 300 mg once daily in patients tolerating Canagliflozin 100 mg once daily who have an eGFR of 60 ml/min/1.73 m2 or greater and require additional glycemic control. If the eGFR of Patients is 45 to 60 ml/min/1.73 m2,the dose of Canagliflozin should be 100 mg once daily.

Side Effects

Dehydration, Vaginal yeast infection, Yeast infection of the penis (balanitis or balanoposthitis)

Toxicity

Overdose information

If an overdose occurs, contact the Poison Control Center. Normal supportive measures should be taken, including the removal unabsorbed drug from the gastrointestinal tract, initiating clinical monitoring of the patient, and providing supportive treatment as deemed necessary. Canagliflozin has been removed in very small quantities after a 4-hour hemodialysis session. This drug is likely not dialyzable by peritoneal dialysis .

Pregnancy and lactation

Animal data has demonstrated that canagliflozin may cause adverse renal effects in a growing fetus. Data are insufficient at this time in determining a potential canagliflozin related risk for major birth defects or possible miscarriage in humans . There are known risks, however, of uncontrolled diabetes in pregnancy . Inform female patients taking canagliflozin of the potential risk, which is increased during the second and third trimesters. This drug is not recommended during nursing .

Mutagenesis and carcinogenicity

Canagliflozin was not found to be mutagenic in both metabolically activated and inactivated states in the Ames assay. Canagliflozin showed mutagenicity in laboratory mouse lymphoma assay, but only in the activated state. Canagliflozin was not found to be mutagenic in several in vivo assays performed on rats .

The carcinogenic risk of canagliflozin was assessed in 2-year studies completed in both CD1 mice and Sprague-Dawley rats. Canagliflozin was not shown to increase tumor incidence in mouse models given doses less than or equal to 14 times the exposure from a typical 300 mg dose in humans. Despite these negative findings in mice, the incidence of several tumors increased in mice, including Leydig cell tumors, renal tubular adenomas, and adrenal pheochromocytomas .

Precaution

Hypotension: Before initiating Canagliflozin, assess volume status and correct hypovolemia in patients with renal impairment, the elderly, in patients with low systolic blood pressure, or if on diuretics, ACEi, or ARB. Monitor for signs and symptoms during therapy.

Impairment in Renal Function: Monitor renal function during therapy. More frequent monitoring is recommended in patients with eGFR below 60 mL/min/1.73 m2. Do not initiate Canagliflozin if eGFR is below 45 mL/min/1.73 m2.

Hyperkalemia: Monitor potassium levels in patients with impaired renal function and in patients predisposed to hyperkalemia.

Hypoglycemia: Consider a lower dose of insulin or the insulin secretagogue to reduce the risk of hypoglycemia when used in combination with Canagliflozin.

Interaction

UGT enzyme inducers: The efficacy of Canagliflozin may be reduced when Co-administered with UGT enzyme inducers (e.g., with rifampin, phenytoin,phenobarbital, ritonavir).There was an increase in the area AUC and mean peak drug concentration (Cmax) of digoxin (20% and 36%, respectively) when co-administered with Canagliflozin.

Volume of Distribution

This drug is extensively distributed throughout the body. On average, the volume of distribution of canagliflozin at steady state following a single intravenous dose in healthy patients was measured to be 83.5 L .

Elimination Route

Bioavailability and steady-state

The absolute oral bioavailability of canagliflozin, on average, is approximately 65% . Steady-state concentrations are achieved after 4 to 5 days of daily dose administration between the range of 100mg to 300mg .

Effect of food on absorption

Co-administration of a high-fat meal with canagliflozin exerted no appreciable effect on the pharmacokinetic parameters of canagliflozin. This drug may be administered without regard to food. Despite this, because of the potential of canagliflozin to decrease postprandial plasma glucose excretion due to prolonged intestinal glucose absorption, it is advisable to take this drug before the first meal of the day .

Half Life

In a clinical study, the terminal half-life of canagliflozin was 10.6 hours for the 100mg dose and 13.1 hours for the 300 mg dose .

Clearance

In healthy subjects, canagliflozin clearance was approximately 192 mL/min after intravenous (IV) administration .

The renal clearance of 100 mg and 300 mg doses of canagliflozin was measured to be in the range of 1.30 - 1.55 mL/min .

Elimination Route

After a single oral radiolabeled dose canagliflozin dose to healthy subjects, the following ratios of canagliflozin or metabolites were measured in the feces and urine :

Feces

41.5% as the unchanged radiolabeled drug

7.0% as a hydroxylated metabolite

3.2% as an O-glucuronide metabolite

Urine

About 33% of the ingested radiolabled dose was measured in the urine, generally in the form of O-glucuronide metabolites. Less than 1% of the dose was found excreted as unchanged drug in urine.

Pregnancy & Breastfeeding use

Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Canagliflozin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known if Canagliflozin passes into breast milk. Discontinue drug or nursing

Contraindication

History of a serious hypersensitivity reaction to Canagliflozin, Severe renal impairment (eGFR less than 30 mL/min/1.73 m2), end stage renal disease or patients on dialysis.

Special Warning

Pediatric Uses: Safety and effectiveness of Canagliflozin in pediatric patients under 18 years of age have not been established.

Geriatric Uses: Patients 65 years and older had a higher incidence of adverse reactions related to reduced intravascular volume with Canagliflozin (such as hypotension, postural dizziness, orthostatic hypotension, syncope, and dehydration).

Storage Condition

Protect from light and moisture. Store below 30°C. Keep medicine out of the reach of children.

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