This eLearning module has been commissioned by Janssen and Napp Pharmaceuticals Limited, and developed in partnership with Guidelines.co.uk. Janssen and Napp Pharmaceuticals Limited reviewed the module to ensure compliance with the ABPI Code of Practice.
This Guidelines eLearning module will highlight some of the key recommendations made in NICE Guideline 28 (NG28) Type 2 diabetes in adults: management pertaining to blood glucose management of patients with type 2 diabetes, with a focus on establishing appropriate HbA1c targets for your patients, and how canagliflozin may be able to help achieve them. At the end of the presentation you will find some questions to measure your learning, and a certificate of completion that you can print out and put in your CPD folder.
Photographs within the eLearning module are for illustration purposes only.
Date of preparation: September 2016
BMI=body mass index; DPP-4i=dipeptidyl peptidase-4 inhibitor; eGFR=estimated glomerular filtration rate; GLP-1=glucagon-like peptide-1; HbA1c=glycated haemoglobin; HDL=high-density lipoprotein; LDL=low-density lipoprotein; LOCF=last observation carried forward; LS=least squares; MHRA=Medicines and Healthcare products Regulatory Agency; SE=standard error; SGLT-2i=Sodium-glucose cotransporter-2 inhibitor; SU=sulfonylurea
This eLearning module includes parts of NICE Guideline 28 (NG28) Type 2 diabetes in adults: management and NICE Technology Appraisal 315 (TA315) Canagliflozin in combination therapy for treating type 2 diabetes; readers are strongly advised to refer to the full guideline and technology appraisal at www.nice.org.uk/guidance/ng28 and www.nice.org.uk/guidance/ta315 respectively.
Footnotes * to ‡ are taken from NICE Guideline 28 (NG28) Type 2 diabetes in adults: management (2015), please consult individual product summaries of product characteristics for further information
* When prescribing pioglitazone, exercise particular caution if the person is at high risk of the adverse effects of the drug. Pioglitazone is associated with an increased risk of heart failure, bladder cancer and bone fracture. Known risk factors for these conditions, including increased age, should be carefully evaluated before treatment: see the manufacturers’ summaries of product characteristics for details. Medicines and Healthcare products Regulatory Agency (MHRA) guidance (2011) advises that ‘prescribers should review the safety and efficacy of pioglitazone in individuals after 3–6 months of treatment to ensure that only patients who are deriving benefit continue to be treated’.
† Treatment with combinations of drugs including sodium–glucose cotransporter 2 inhibitors may be appropriate for some people at first and second intensification; see NICE technology appraisal guidance 288, 315, and 336 on dapagliflozin▼, canagliflozin▼, and empagliflozin▼ respectively.2–4 All three SGLT-2 inhibitors are recommended as options in dual therapy regimens with metformin under certain conditions.2–4 All three are also recommended as options in combination with insulin.2–4 At the time of publication, only canagliflozin and empagliflozin are recommended as options in triple therapy regimens.3,4 The role of dapagliflozin in triple therapy will be reassessed by NICE in a partial update of TA288. Serious and life-threatening cases of diabetic ketoacidosis have been reported in people taking SGLT-2 inhibitors (canagliflozin, dapagliflozin, or empagliflozin) or shortly after stopping the SGLT-2 inhibitor. MHRA guidance (2016)5 advises testing for raised ketones in people with symptoms of diabetic ketoacidosis, even if plasma glucose levels are near normal.
‡ Only continue GLP-1 mimetic therapy if the person has a beneficial metabolic response (a reduction of HbA1c by at least 11 mmol/mol [1.0%] and a weight loss of at least 3% of initial body weight in 6 months).
§ Canagliflozin is not indicated for weight loss or the treatment of hypertension.
| Pre-specified secondary endpoint.
¶ The four placebo-controlled trials included one monotherapy and three add-on combination trials with metformin, metformin and sulfonylurea, or metformin and pioglitazone.
- NICE. Type 2 diabetes in adults: management. NICE Guideline 28. NICE, 2015. Available at: www.nice.org.uk/guidance/ng28
- NICE. Dapagliflozin in combination therapy for treating type 2 diabetes. Technology Appraisal 288. NICE, 2013. Available at: www.nice.org.uk/guidance/ta288
- NICE. Canagliflozin in combination therapy for treating type 2 diabetes. Technology Appraisal 315. NICE, 2014. Available at: www.nice.org.uk/guidance/ta315
- NICE. Empagliflozin in combination therapy for treating type 2 diabetes. Technology Appraisal 336. NICE, 2015. Available at: www.nice.org.uk/guidance/ta336
- Medicines and Healthcare products Regulatory Agency. SGLT2 inhibitors: updated advice on the risk of diabetic ketoacidosis. MHRA, 2016. Available at: www.gov.uk/drug-safety-update/sglt2-inhibitors-updated-advice-on-the-risk-of-diabetic-ketoacidosis
- Scottish Medicines Consortium. Canagliflozin, 100mg and 300mg film-coated tablets (Invokana). SMC No. (964/14). Glasgow: SMC, 2014. Available at: www.scottishmedicines.org.uk/files/advice/M__Scottish_Medicine_Consortium_Web_Data_Audit_advice_Advice_by_Year_2014_No.6_-_June_2014_canaglaflozin__Invokana__FINAL_May_2014_for_website.pdf
- Janssen-Cilag Ltd. Invokana 100 mg film-coated tablets—summary of product characteristics. www.medicines.org.uk/emc/medicine/28400
- Janssen-Cilag Ltd. Invokana 300 mg film-coated tablets—summary of product characteristics. www.medicines.org.uk/emc/medicine/28401
- Lavalle-Gonzalez E, Januszewicz A, Davidson J et al. Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomized trial. Diabetologia 2013; 56: 2582–2592.
- Usiskin K, Kline I, Fung A et al. Safety and tolerability of canagliflozin in patients with type 2 diabetes mellitus: pooled analysis of phase 3 study results. Postgrad Med 2014; 126 (3): 16–34.
- European Medicines Agency. EMA confirms recommendations to minimize ketoacidosis risk with SGLT2 inhibitors for diabetes. EMA, 2016. Available at: www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/SGLT2_inhibitors/human_referral_prac_000052.jsp&mid=WC0b01ac05805c516f
- Leiter L, Yoon K, Arias P et al. Canagliflozin provides durable glycemic improvements and body weight reduction over 104 weeks versus glimepiride in patients with type 2 diabetes on metformin: a randomized, double-blind, phase 3 study. Diabetes Care 2015; 38: 355–364.
- Bacon T, Willis M, Johansen P, Neslusan C. Poster presented at the 20th Annual Meeting of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR); 2015; May 16-20; Philadelphia, Pennsylvania, USA [PDB17].
- Novo Nordisk Limited. Changing Diabetes Barometer—First Report. Novo Nordisk, 2007.
- Taieb V, Pacou M, Schroeder M et al. Poster presented at the 18th Annual Meeting of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR); 2015; November 7–11; Milan, Italy [PDB5].
- Monthly Index of Medical Specialities. MIMS online. Haymarket Medical Media, 2016. www.mims.co.uk
- Diets J, Neslusan C. Poster presented at the 20th Annual Meeting of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR); 2015; May 16-20; Philadelphia, Pennsylvania, USA [PDB91].
INVOKANA®▼ film-coated tablets PRESCRIBING INFORMATION
ACTIVE INGREDIENT(S): Canagliflozin hemihydrate, equivalent to 100 mg or 300 mg canagliflozin.
Please refer to Summary of Product Characteristics (SmPC) before prescribing.
INDICATION(S): In adults with type 2 diabetes mellitus to improve glycaemic control as: monotherapy when diet and exercise alone do not provide adequate glycaemic control and use of metformin considered inappropriate; add-on therapy with other glucose‑lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control.
DOSAGE & ADMINISTRATION: Adults: recommended starting dose: 100 mg once daily. In patients tolerating this dose and with eGFR ≥ 60 mL/min/1.73 m2 needing tighter glycaemic control, dose can be increased to 300 mg once daily. Caution increasing dose in patients ≥ 75 years old, with known cardiovascular disease or for whom initial canagliflozin-induced diuresis is a risk. Correct volume depletion prior to initiation. When add-on, consider lower dose of insulin or insulin secretagogue to reduce risk of hypoglycaemia. Children: no data available. Elderly: consider renal function and risk of volume depletion. Renal impairment: not to be initiated with eGFR < 60 mL/min/1.73 m2. If eGFR falls below this value during treatment, adjust or maintain dose at 100 mg once daily. Discontinue if eGFR persistently < 45 mL/min/1.73 m2. Not for use in end stage renal disease or patients on dialysis. Hepatic impairment: mild or moderate hepatic impairment: no dose adjustment. Severe hepatic impairment: not studied, not recommended.
CONTRAINDICATIONS: Hypersensitivity to active substance or any excipient.
SPECIAL WARNINGS & PRECAUTIONS: Not for use in type 1 diabetes. Not to be used for treatment of diabetic ketoacidosis. Renal impairment: eGFR < 60 mL/min/1.73 m2: higher incidence of ADRs associated with volume depletion particularly with 300 mg dose; more events of elevated potassium; greater increases in serum creatinine and BUN; limit dose to 100 mg once daily and discontinue when eGFR < 45 mL/min/1.73 m2. Not studied in severe renal impairment. Monitor renal function prior to initiation and at least annually. Volume depletion: caution in patients for whom a canagliflozin-induced drop in blood pressure is a risk (eg, known cardiovascular disease, eGFR < 60 mL/min/1.73 m2, anti-hypertensive therapy with history of hypotension, on diuretics or elderly people). Not recommended with loop diuretics or volume depleted patients. Monitor volume status and serum electrolytes. Elevated haematocrit: caution. Genital mycotic infections: risk in male and female patients, particularly in those with a history of GMI. Urine laboratory assessment: glucose in urine due to mechanism of action. Lactose intolerance: do not use in patients with galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. Diabetic ketoacidosis (DKA): rare DKA cases reported, including life-threatening and atypical presentation cases. Where DKA is suspected or diagnosed, discontinue Invokana treatment immediately. Interrupt treatment in patients who are undergoing major surgical procedures or have acute serious medical illnesses. Consider risk factors for development of DKA before initiating Invokana treatment.
SIDE EFFECTS: Very common: hypoglycaemia in combination with insulin or sulphonylurea, vulvovaginal candidiasis. Common: constipation, thirst, nausea, polyuria or pollakiuria, urinary tract infection (including pyelonephritis and urosepsis), balanitis or balanoposthitis, dyslipidemia, haematocrit increased. Uncommon: dehydration, postural dizziness, syncope, hypotension, orthostatic hypotension, rash, urticaria, bone fracture, renal failure (mainly in the context of volume depletion). Other side effects: angioedema, diabetic ketoacidosis, anaphylactic reaction.
Refer to SmPC for other side effects.
PREGNANCY: No human data. Not recommended.
LACTATION: Unknown if excreted in human milk. Should not be used during breast-feeding.
INTERACTIONS: Diuretics: may increase risk of dehydration and hypotension. Insulin and insulin secretagogues: risk of hypoglycaemia; consider lower dose of insulin or insulin secretagogue. Effects of other medicines on Invokana: Enzyme inducers (eg, St. John’s wort, rifampicin, barbiturates, phenytoin, carbamazepine, ritonavir, efavirenz) may decrease exposure of canagliflozin; monitor glycaemic control. Consider dose increase to 300 mg if administered with UGT enzyme inducer. Cholestyramine may reduce canagliflozin exposure; take canagliflozin at least 1 hour before or 4-6 hours after a bile acid sequestrant. Effects of Invokana on other medicines: Monitor patients on digoxin, other cardiac glycosides, dabigatran. Inhibition of Breast Cancer Resistance Protein cannot be excluded; possible increased exposure of drugs transported by BCRP (eg, rosuvastatin and some anti-cancer agents).
Refer to SmPC for full details of interactions.
LEGAL CATEGORY: POM
PRESENTATIONS, PACK SIZES, MARKETING AUTHORISATION NUMBER(S) & BASIC NHS COSTS
|Invokana 100 mg film-coated tablets||30 tablets||EU/1/13/884/002||£39.20|
|Invokana 300 mg film-coated tablets||30 tablets||EU/1/13/884/006||£39.20|
MARKETING AUTHORISATION HOLDER: Janssen-Cilag International NV, Turnhoutseweb 30, B-2340 Beerse, Belgium.
FURTHER INFORMATION IS AVAILABLE FROM: Janssen-Cilag Limited, 50–100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG UK.
Prescribing information last revised: June 2016
|Adverse events should be reported. ▼ This medicinal product is subject to additional monitoring and it is therefore important to report any suspected adverse events related to this medicinal product. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Janssen-Cilag Limited on 01494 567447 or at email@example.com.|