INVOKANA- canagliflozin tablet, film coated

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

CANAGLIFLOZIN (UNII: 0SAC974Z85) (CANAGLIFLOZIN ANHYDROUS - UNII:6S49DGR869)

Available from:

A-S Medication Solutions

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

INVOKANA (canagliflozin) is indicated: - as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. - to reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease (CVD). - to reduce the risk of end-stage kidney disease (ESKD), doubling of serum creatinine, cardiovascular (CV) death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria greater than 300 mg/day. Limitations of Use INVOKANA is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus [see Warnings and Precautions (5.1)] . INVOKANA is not recommended for use to improve glycemic control in adults with type 2 diabetes mellitus with an eGFR less than 30 mL/min/1.73 m 2 . INVOKANA is likely to be ineffective in this setting based upon its mechanism of action. INVOKANA is contraindicated in patients with a serious hypersensitivity reaction to INVOKANA, such as anaphylaxis or angioedema [see Warnings and Precautions (5.8)and Adverse Reactions (6.1, 6.2)] . Risk Summary Based on animal data showing adverse renal effects, INVOKANA is not recommended during the second and third trimesters of pregnancy. Limited data with INVOKANA in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see Clinical Considerations]. In animal studies, adverse renal pelvic and tubule dilatations that were not reversible were observed in rats when canagliflozin was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy, at an exposure 0.5-times the 300 mg clinical dose, based on AUC. The estimated background risk of major birth defects is 6–10% in women with pre-gestational diabetes with a HbA 1C >7 and has been reported to be as high as 20–25% in women with a HbA 1C >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. Animal Data Canagliflozin dosed directly to juvenile rats from postnatal day (PND) 21 until PND 90 at doses of 4, 20, 65, or 100 mg/kg increased kidney weights and dose dependently increased the incidence and severity of renal pelvic and tubular dilatation at all doses tested. Exposure at the lowest dose was greater than or equal to 0.5-times the 300 mg clinical dose, based on AUC. These outcomes occurred with drug exposure during periods of renal development in rats that correspond to the late second and third trimester of human renal development. The renal pelvic dilatations observed in juvenile animals did not fully reverse within a 1-month recovery period. In embryo-fetal development studies in rats and rabbits, canagliflozin was administered for intervals coinciding with the first trimester period of organogenesis in humans. No developmental toxicities independent of maternal toxicity were observed when canagliflozin was administered at doses up to 100 mg/kg in pregnant rats and 160 mg/kg in pregnant rabbits during embryonic organogenesis or during a study in which maternal rats were dosed from gestation day (GD) 6 through PND 21, yielding exposures up to approximately 19-times the 300 mg clinical dose, based on AUC. Risk Summary There is no information regarding the presence of INVOKANA in human milk, the effects on the breastfed infant, or the effects on milk production. Canagliflozin is present in the milk of lactating rats [see Data] . Since human kidney maturation occurs in utero and during the first 2 years of life when lactational exposure may occur, there may be risk to the developing human kidney. Because of the potential for serious adverse reactions in a breastfed infant, advise women that use of INVOKANA is not recommended while breastfeeding. Data Animal Data Radiolabeled canagliflozin administered to lactating rats on day 13 post-partum was present at a milk/plasma ratio of 1.40, indicating that canagliflozin and its metabolites are transferred into milk at a concentration comparable to that in plasma. Juvenile rats directly exposed to canagliflozin showed a risk to the developing kidney (renal pelvic and tubular dilatations) during maturation. Safety and effectiveness of INVOKANA in pediatric patients under 18 years of age have not been established. In 13 clinical trials of INVOKANA, 2,294 patients 65 years and older, and 351 patients 75 years and older were exposed to INVOKANA [see Clinical Studies (14.1)] . Patients 65 years and older had a higher incidence of adverse reactions related to reduced intravascular volume with INVOKANA (such as hypotension, postural dizziness, orthostatic hypotension, syncope, and dehydration), particularly with the 300 mg daily dose, compared to younger patients; a more prominent increase in the incidence was seen in patients who were 75 years and older [see Dosage and Administration (2.1)and Adverse Reactions (6.1)]. Smaller reductions in HbA 1C with INVOKANA relative to placebo were seen in older (65 years and older; -0.61% with INVOKANA 100 mg and -0.74% with INVOKANA 300 mg relative to placebo) compared to younger patients (-0.72% with INVOKANA 100 mg and -0.87% with INVOKANA 300 mg relative to placebo). The efficacy and safety of INVOKANA for glycemic control were evaluated in a trial that included patients with moderate renal impairment (eGFR 30 to less than 50 mL/min/1.73 m 2 ) [see Clinical Studies (14.1)] . These patients had less overall glycemic efficacy, and patients treated with 300 mg per day had increases in serum potassium, which were transient and similar by the end of study. Patients with renal impairment using INVOKANA for glycemic control may also be more likely to experience hypotension and may be at higher risk for acute kidney injury [see Warnings and Precautions (5.3)] . Efficacy and safety studies with INVOKANA did not enroll patients with ESKD on dialysis or patients with an eGFR less than 30 mL/min/1.73 m 2 [see Clinical Pharmacology (12.3)] . No dosage adjustment is necessary in patients with mild or moderate hepatic impairment. The use of INVOKANA has not been studied in patients with severe hepatic impairment and is therefore not recommended [see Clinical Pharmacology (12.3)] .

Product summary:

Product: 50090-4364 NDC: 50090-4364-0 90 TABLET, FILM COATED in a BOTTLE

Authorization status:

New Drug Application

Patient Information leaflet

A-S Medication Solutions
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This Medication Guide has been approved by the U.S. Food and Drug
Administration.
Revised: 07/2023
Medication Guide
INVOKANA ®(in-vo-KAHN-uh)
(canagliflozin)
tablets, for oral use
What is the most important information I should know about INVOKANA?
INVOKANA can cause serious side effects, including:
•
Diabetic ketoacidosis (increased ketones in your blood or urine) in
people with type 1 and other
ketoacidosis.INVOKANA can cause ketoacidosis that can be
life-threatening and may lead to
death. People with type 1 diabetes, type 2 diabetes, or pancreas
problems have a high risk of
getting ketoacidosis. Ketoacidosis can happen even if your blood sugar
is less than 250 mg/dL.
Your healthcare provider may ask you to periodically check ketones in
your urine or blood.
Ketoacidosis can also happen in people who are sick or who have
surgery during treatment with
INVOKANA. Ketoacidosis is a serious condition which needs to be
treated in a hospital.
Ketoacidosis may lead to death.
•
Stop taking INVOKANA and call your healthcare provider or get medical
help right away if you
get any of the following. If possible, check for ketones in your urine
or blood, even if your blood
sugar is less than 250 mg/dL:
•
nausea
•
vomiting
•
stomach-area (abdominal) pain
•
tiredness
•
trouble breathing
•
ketones in your urine or
blood
•
Amputations. INVOKANA may increase your risk of lower limb
amputations. Amputations
mainly involve removal of the toe or part of the foot, however,
amputations involving the leg,
below and above the knee, have also occurred. Some people had more
than one amputation, some
on both sides of the body.
You may be at a higher risk of lower limb amputation if you:
•
have a history of amputation
•
have heart disease or are at risk for heart disease
•
have had blocked or narrowed blood vessels, usually in your leg
•
have damage to the nerves (neuropathy) in your leg
•
have had diabetic foot ulcers or sores
Call your doctor right away if you have new pain or

Summary of Product characteristics

INVOKANA- CANAGLIFLOZIN TABLET, FILM COATED
A-S MEDICATION SOLUTIONS
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
INVOKANA SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR INVOKANA.
INVOKANA
(CANAGLIFLOZIN) TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2013
RECENT MAJOR CHANGES
Indications and Usage ( 1)
07/2023
Dosage and Administration ( 2)
07/2023
Contraindications ( 4)
07/2023
Warnings and Precautions ( 5.1)
07/2023
INDICATIONS AND USAGE
INVOKANA is a sodium-glucose co-transporter 2 (SGLT2) inhibitor
indicated:
As an adjunct to diet and exercise to improve glycemic control in
adults with type 2 diabetes mellitus (
1)
To reduce the risk of major adverse cardiovascular events in adults
with type 2 diabetes mellitus and
established cardiovascular disease ( 1)
To reduce the risk of end-stage kidney disease, doubling of serum
creatinine, cardiovascular death, and
hospitalization for heart failure in adults with type 2 diabetes
mellitus and diabetic nephropathy with
albuminuria ( 1).
Limitations of Use:
Not recommended for use to improve glycemic control in patients with
type 1 diabetes mellitus ( 1)
Not recommended for use to improve glycemic control in adults with
type 2 diabetes mellitus with an
eGFR less than 30 mL/min/1.73 m
( 1)
DOSAGE AND ADMINISTRATION
Assess renal function before initiating and as clinically indicated (
2.1)
The recommended starting dose is 100 mg once daily, taken before the
first meal of the day ( 2.2)
Dose can be increased to 300 mg once daily in patients tolerating 100
mg once daily who have an eGFR
of 60 mL/min/1.73 m
or greater and require additional glycemic control ( 2.2)
Dose adjustment for patients with renal impairment may be required (
2.3)
See full prescribing information for INVOKANA dosage modifications due
to drug interactions ( 2.4)
Withhold INVOKANA at least 3 days, if possible, prior to major surgery
or procedures associated with
prolonged fasting ( 2.5).
DOSAGE FORMS AND STRENGTHS
Tablets: