Invokana

Invokana Special Precautions

canagliflozin

Manufacturer:

Janssen

Distributor:

Zuellig Pharma
Full Prescribing Info
Special Precautions
General: Invokana has not been studied in patients with type 1 diabetes and is therefore not recommended for use in these patients.
Invokana should not be used for the treatment of diabetic ketoacidosis as it is not effective in this setting.
Use in Patients with Renal Impairment: The efficacy of canagliflozin is dependent on renal function, and efficacy is reduced in patients who have moderate renal impairment and likely absent in patients with severe renal impairment (see Dosage & Administration).
In patients with an eGFR <60 mL/min/1.73 m2 or CrCl <60 mL/min, a higher incidence of adverse reactions associated with volume depletion (e.g., postural dizziness, orthostatic hypotension, hypotension) was reported, particularly with the 300 mg dose. In addition, in such patients more events of elevated potassium and greater increases in serum creatinine and blood urea nitrogen (BUN) were reported (see Adverse Reactions).
Therefore, the canagliflozin dose should be limited to 100 mg once daily in patients with eGFR <60 mL/min/1.73 m2 or CrCl <60 mL/min and canagliflozin should not be used in patients with an eGFR <45 mL/min/1.73 m2 or CrCl <45 mL/min (see Dosage & Administration). Canagliflozin has not been studied in severe renal impairment (eGFR <30 mL/min/1.73 m2 or CrCl <30 mL/min) or ESRD.
Monitoring of Renal Function is Recommended As Follows: Prior to initiation of canagliflozin and at least annually, thereafter (see Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions, Dosage & Administration and Adverse Reactions); prior to initiation of concomitant medicinal products that may reduce renal function and periodically thereafter; for renal function approaching moderate renal impairment, at least 2 times to 4 times per year. If renal function falls persistently below eGFR 45 mL/min/1.73 m2 or CrCl <45 mL/min, canagliflozin treatment should be discontinued.
Use in Patients At Risk for Adverse Reactions Related to Volume Depletion: Due to its mechanism of action, canagliflozin, by increasing urinary glucose excretion (UGE) induces an osmotic diuresis, which may reduce intravascular volume and decrease blood pressure (see Pharmacology: Pharmacodynamics under Actions). In controlled clinical studies of canagliflozin, increases in adverse reactions related to volume depletion (e.g., postural dizziness, orthostatic hypotension, or hypotension) were seen more commonly with the 300 mg dose and occurred most frequently in the first three months (see Adverse Reactions).
Caution should be exercised in patients for whom a canagliflozin-induced drop in blood pressure could pose a risk, such as patients with known cardiovascular disease, patients with an eGFR <60 mL/min/1.73 m2, patients on anti-hypertensive therapy with a history of hypotension, patients on diuretics, or elderly patients (≥65 years of age) (see Dosage & Administration and Adverse Reactions).
Due to volume depletion, generally small mean decreases in eGFR were seen within the first 6 weeks of treatment initiation with canagliflozin. In patients susceptible to greater reductions in intravascular volume as described above, larger decreases in eGFR (>30%) were sometimes seen, which subsequently improved, and infrequently required interruption of treatment with canagliflozin (see Adverse Reactions).
Patients should be advised to report symptoms of volume depletion. Canagliflozin is not recommended for use in patients receiving loop diuretics (see Interactions) or who are volume depleted, e.g., due to acute illness (such as gastrointestinal illness).
For patients receiving canagliflozin, in case of intercurrent conditions that may lead to volume depletion (such as a gastrointestinal illness), careful monitoring of volume status (e.g., physical examination, blood pressure measurements, laboratory tests including renal function tests), and serum electrolytes is recommended. Temporary interruption of treatment with canagliflozin may be considered for patients who develop volume depletion while on canagliflozin therapy until the condition is corrected. If interrupted, consideration should be given to more frequent glucose monitoring.
Elevated Haematocrit: Haematocrit increase was observed with canagliflozin treatment (see Adverse Reactions); therefore, caution in patients with already elevated haematocrit is warranted.
Elderly (≥65 Years Old): Elderly patients may be at a greater risk for volume depletion, are more likely to be treated with diuretics, and to have impaired renal function. In patients ≥75 years of age, a higher incidence of adverse reactions associated with volume depletion (e.g., postural dizziness, orthostatic hypotension, hypotension) was reported. In addition, in such patients greater decreases in eGFR were reported (see Dosage & Administration and Adverse Reactions).
Genital Mycotic Infections: Consistent with the mechanism of sodium glucose co-transporter 2 (SGLT2) inhibition with increased UGE, vulvovaginal candidiasis in females and balanitis or balanoposthitis in males were reported in clinical trials (see Adverse Reactions). Male and female patients with a history of genital mycotic infections were more likely to develop an infection. Balanitis or balanoposthitis occurred primarily in uncircumcised male patients. In rare instances, phimosis was reported and sometimes circumcision was performed. The majority of genital mycotic infections were treated with topical antifungal treatments, either prescribed by a healthcare professional or self-treated while continuing therapy with Invokana.
Cardiac Failure: Experience in New York Heart Association (NYHA) class III is limited, and there is no experience in clinical studies with canagliflozin in NYHA class IV.
Urine Laboratory Assessments: Due to its mechanism of action, patients taking canagliflozin will test positive for glucose in their urine.
Lactose Intolerance: The tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.
Diabetic Ketoacidosis: Rare cases of diabetic ketoacidosis (DKA), including life-threatening cases, have been reported in clinical trials and post-marketing in patients treated with SGLT2 inhibitors, including canagliflozin. In a number of cases, the presentation of the condition was atypical with only moderately increased blood glucose values, below 14 mmol/l (250 mg/dl). It is not known if DKA is more likely to occur with higher doses of canagliflozin.
The risk of diabetic ketoacidosis must be considered in the event of non-specific symptoms such as nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual fatigue or sleepiness. Patients should be assessed for ketoacidosis immediately if these symptoms occur, regardless of blood glucose level.
In patients where DKA is suspected or diagnosed, treatment with canagliflozin should be discontinued immediately.
Treatment should be interrupted in patients who are hospitalized for major surgical procedures or acute serious medical illnesses. In both cases, treatment with canagliflozin may be restarted once the patient’s condition has stabilized.
Before initiating canagliflozin, factors in the patient history that may predispose to ketoacidosis should be considered.
Patients who may be at higher risk of DKA include patients with a low beta-cell function reserve (e.g., type 2 diabetes patients with low C-peptide or latent autoimmune diabetes in adults (LADA) or patients with a history of pancreatitis), patients with conditions that lead to restricted food intake or severe dehydration, patients for whom insulin doses are reduced and patients with increased insulin requirements due to acute medical illness, surgery or alcohol abuse. SGLT2 inhibitors should be used with caution in these patients.
Restarting SGLT2 inhibitor treatment in patients with previous DKA while on SGLT2 inhibitor treatment is not recommended unless another clear precipitating factor is identified and resolved.
The safety and efficacy of canagliflozin in patients with type 1 diabetes have not been established and canagliflozin should not be used for treatment of patients with type 1 diabetes. Limited data from clinical trials suggest that DKA occurs with common frequency when patients with type 1 diabetes are treated with SGLT2 inhibitors.
Effects on Ability to Drive and Use Machines: Canagliflozin has no or negligible influence on the ability to drive and use machines. However, patients should be alerted to the risk of hypoglycaemia when canagliflozin is used as add-on therapy with insulin or an insulin secretagogue, and to the elevated risk of adverse reactions related to volume depletion, such as postural dizziness (see Dosage & Administration, Precautions and Adverse Reactions).
Fertility: The effect of canagliflozin on fertility in humans has not been studied. No effects on fertility were observed in animal studies (see Pharmacology: Toxicology: Preclinical Safety Data under Actions).
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