Optimal management of
diabetic kidney disease:
hypertension and glycaemia
SECTION F
These slides were sponsored by Janssen and developed in conjunction with the BRS CKD Strategy Group, following an advisory board that
was organised by Janssen. Bedrock Healthcare Communications provided editorial support to members of the advisory board in developing
the slides. Janssen reviewed the content for technical accuracy. The content is intended for a UK healthcare professional audience only.
JOB CODE PHGB/VOK/0914/0018e
Date of preparation: January 2015
Objectives and background for this learning resource
Introduction:
This learning resource has been developed as part of a medical education initiative supported by
Janssen. The content of this slide kit has been developed by an advisory board of renal physicians, GPs
and specialist nurses. The panel of experts includes members of the British Renal Society Chronic Kidney
Disease (CKD) Strategy Group. Bedrock Healthcare, a medical communications agency, has provided
editorial support in developing the content; Janssen has reviewed the content for technical accuracy.
Educational objectives:
•
To provide clear and applicable clinical guidance on chronic kidney disease (CKD) in people with type
2 diabetes to primary care healthcare professionals
•
To advise primary healthcare professionals on what people with diabetes need to know about their
own condition with relation to CKD
Usability objectives:
•
To provide essential, relevant and up to date information in concise presentations
•
To enable primary healthcare professionals to locate, select and use the content of the learning
resource, as appropriate to their needs
•
To enable secondary care experts in CKD to refer their primary care colleagues to the resource
1
Contents overview
This learning resource comprises the following 10 sections (A-E):
Section A
Introduction and overview of chronic kidney disease (CKD) in people
with diabetes
Section B
Long-term impact of diabetes and the importance of optimal
management of the condition
Section C
Pathophysiology of diabetic nephropathy & risk factors for the
development of CKD
Section D
Appropriate monitoring for complications of diabetes in primary care –
CKD as one of these complications
Section E
Prevention of diabetic kidney disease
2
Contents overview (cont.)
This learning resource comprises the following 10 sections (F-J):
Section F
Optimal management of diabetic kidney disease:
hypertension and glycaemia
Section G
How to involve people with diabetes and CKD in their own care – what
information must they have to manage their own condition effectively?
Section H
What does the future hold for a person with well-managed diabetes
and CKD?
Section I
What do the guidelines say and what do they mean in terms of the
day-to-day management of CKD in people with diabetes?
Section J
Sources of further information and reading list
3
Section F – 3 key learning objectives
• Once diabetic kidney disease has developed, early optimal management can
reduce disease progression
• ACE inhibitors and ARBs improve outcomes
• Presence of diabetic kidney disease implies generalised vascular disease
which requires holistic management
4
ACE inhibitors or ARBs for blood pressure
management
• Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor
blockers (ARBs) are both renin–angiotensin–aldosterone system (RAAS)
antagonists1
• Only one type of RAAS agonist should be offered to people with CKD
– Combined therapy of ACE inhibitors and ARBs is not recommended1
Reference:
1. NICE clinical guideline 182. Chronic kidney disease early identification and management of chronic kidney disease in adults in primary and secondary care. July 2014.
5
ACE inhibitors or ARBs may reduce the rate of GFR
decline
ACEI/ARB
given
Long-term slowing of reduction in GFR
in people with proteinuria and normal
renal perfusion
eGFR
Slowly
deteriorating CKD
Continued rapid fall in GFR when there
is renovascular disease or other cause
of global reduction in renal perfusion
Acute reduction eGFR – expected
(medication need not necessarily
be stopped if reduction less than
25%1)
Time
Figure created from discussions with the advisory board
Reference:
1. NICE clinical guideline 182. Chronic kidney disease early identification and management of chronic kidney disease in adults in primary and secondary care. July 2014.
6
Mode of action of ACE inhibitors and ARBs:
overview of mechanisms
ACE inhibitors
or ARBs
Glomerulosclerosis
Inhibitory
action
Intraglomerular
hypertension
Decline in
RENAL FUNCTION
Reduction in
number of functioning
glomeruli
Increased blood flow to
remaining nephrons
Figure created from discussions with the advisory board and El-Atat FA et al. 2004.1
References:
1. El-Atat FA, et al. The Relationship between Hyperinsulinemia, Hypertension and Progressive Renal Disease. J Am Soc Nephrol 2004;15: 2816–2827.
7
Mode of action of ACE inhibitors and ARBs:
Mechanisms in detail
Systemic Hypertension
Diabetes
BLOCKS
CONVERSION
ANG I TO ANG II
ACE
inhibitors
or ARBs
 Pgc
 SNGFR
Mechanical Stress
 No. of functioning
glomeruli
Ang II
Albuminuria
Macrophages
Fibroblasts
2° FSGS
and TIF
Pgc = glomerular capillary hydraulic pressure
SNGFR = single nephron glomerular filtration rate
Ang II = angiotensin II
2°FSGS = secondary focal segmental glomerulosclerosis
TIF = tubulointerstitial fibrosis;
TGF- = transforming growth factor 
CAMs = chorioallantoic membranes
Figure created from discussions with the advisory board
TGF-
Cytokines
CAMs
Decline in RENAL FUNCTION
8
Hypertension: choice of agents
•
•
Target BP for people with:
CKD: systolic BP <140 mmHg / diastolic BP <90 mmHg1
CKD and diabetes, and ACR ≥70 mg/mmol: systolic BP <130 mmHg / diastolic BP <80 mmHg1
CKD (any stage) +
•
eGFR≤59, diabetes and
ACR*≥3mg/mmol1
•
Hypertension and
ACR ≥30mg/mmol1
•
ACR ≥70mg/mmol1
•
Under 55yrs
(regardless of proteinuria)*
ACE inhibitor, ARB,
direct renin inhibitor or
aldosterone antagonist1
•
Over 55yrs2
•
African or Caribbean family
origin (regardless of age)2
Calcium channel
blocker first line2
*Advice from the advisory board
*ACR=albumin:creatinine ratio
References:
1. NICE clinical guideline 182. Chronic kidney disease early identification and management of chronic kidney disease in adults in primary and secondary care. July 2014.
2. NICE clinical guideline 127. Clinical management of primary hypertension in adults. August 2011.
9
Hypoglycaemia is a risk for patients with type 2 diabetes
and CKD when taking oral glucose control therapies
• Progressive CKD increases the risk
of hypoglycaemia1,2
• With impaired kidney function, the
half-life of insulin is prolonged1,3
• Risk of ‘hypos’ may be more difficult
to predict in patients with CKD*
• Symptoms of ‘hypos’ may be
reduced in patients with CKD*
Always ask about
hypoglycaemia*
• Assess ‘risk and treatment’
of hypoglycaemia1,2
• More tailored dosing is required1
• Patients need to be monitored
more frequently1
Perform frequent therapy
reviews, especially if patient
commences dialysis*
References:
*Advice from the advisory board
1. Cavanaugh KL. Clinical Diabetes 2007;25(3):90-97.
2. National Kidney Foundation KDOQI Clinical Practice Guidelines for Diabetes and CKD: 2012 Update. Available at http://www.kidney.org/sites/default/files/docs/diabetes-ckdupdate-2012.pdf. Website last accessed on 12.11.14.
3. Iglesias P & Diez JJ. Diabetes, Obesity and Metabolism 2008;10:811–823.
10
Importance of testing for anaemia and monitoring
HbA1c levels carefully
• People with CKD are often anaemic, particularly if eGFR <45ml/min/1.73 m2
(GFR category G3b, G4 or G5)1
• Patients with anaemia (defined as Hb <110g/L):1,2
– Have shortened red blood cell (RBC) lifespan (~ 90 days), which reduces
HbA1c levels3
– Have iron deficiency, which increases HbA1c (false high)4
– Are often receiving IV iron therapy or erythropoiesis-stimulating agents (ESA),
both of which can reduce HbA1c in patients with diabetes and CKD5
• It is important to test for anaemia in patients with CKD and monitor HbA1c
levels carefully
References:
1. NICE clinical guideline 182. Chronic kidney disease early identification and management of chronic kidney disease in adults in primary and secondary care. July 2014.
2. NICE clinical guideline 114. Anaemia management in people with chronic kidney disease. February 2011.
3. Joy MS et al, Am J Kidney Dis. 2002 Feb;39(2):297-307.
4. Kim C et al. Diabetes Care 33:780–785, 2010.
5. Ng JM. Diabetes Care 33:2310–2313, 2010
11
Glucose control therapies in type 2 diabetes and CKD
(1 of 4)
Medication
Recommended use in renal impairment
Metformin
• ADULT and CHILD >10 years initially 500 mg with breakfast for at least 1 week then 500 mg with
breakfast and evening meal for at least 1 week then 500 mg with breakfast, lunch and evening meal;
usual max. 2 g daily in divided doses1
• Use with caution in renal impairment, avoid in significant renal impairment1
• Determine renal function before treatment and at least annually (at least twice a year in patients with
additional risk factors for renal impairment, or if deterioration suspected) 1
• NICE recommends dose review if eGFR <45 mL/minute/1.73 m2, avoid if eGFR <30 mL/minute/1.73 m2
• Withdraw or interrupt treatment in those at risk of tissue hypoxia or sudden deterioration in renal function,
such as those with dehydration, severe infection, shock, sepsis, acute heart failure, respiratory failure or
hepatic impairment, or those who have recently had a myocardial infarction 1
DPP4 inhibitors
• Alogliptin1
– Reduce dose to 12.5 mg OD if eGFR 30–50 mL/minute/1.73 m2
– Reduce dose to 6.25 mg OD if eGFR <30 mL/minute/1.73 m2 and use with caution
• Linagliptin1
– ADULT >18 years, 5 mg OD
• Vildagliptin1
– Reduced dose to 50 mg OD if eGFR less than 50 mL/minute/1.73 m2
• Sitagliptin1
– Reduced dose to 50 mg OD if eGFR 30–50 mL/minute/1.73 m2
– Reduced dose to 25 mg OD if eGFR <30 mL/minute/1.73 m2
• Saxagliptin1
– Reduced dose to 2.5 mg OD in moderate to severe impairment
– Use with caution in severe impairment
– Determine renal function before treatment and periodically thereafter
ALL1: Dose of concomitant sulfonylurea or insulin may need to be reduced
References:
1. British National Formulary 2015. Available at: https://www.medicinescomplete.com/about/subscribe.htm Website accessed 03.02.15.
12
Glucose control therapies in type 2 diabetes and CKD
(2 of 4)
Medication
Sulphonylureas
Recommended use in renal impairment
• Glibenclamide1
– Initially 5 mg daily with or immediately after breakfast, dose adjusted according to response (ELDERLY
avoid); max. 15 mg daily
• Gliclazide1
– Initially, 40–80 mg daily, adjusted according to response; up to 160 mg as a single dose, with breakfast;
higher doses divided; max. 320 mg daily
• Glimepiride1
– Initially 1 mg daily, adjusted according to response in 1 mg steps at 1–2 week intervals; usual max.
4 mg daily (exceptionally, up to 6 mg daily may be used); taken shortly before or with first main meal
• Glipizide1
– Initially 2.5–5 mg daily shortly before breakfast/lunch, adjusted according to response; max. 20 mg daily;
up to 15 mg may be given as a single dose; higher doses divided
• Tolbutamide1
– 0.5–1.5 g (max. 2 g) daily in divided doses with or immediately after meals or as a single dose with or
immediately after breakfast
ALL1: Use with care in those with mild to moderate renal impairment, due to hypoglycaemia; avoid where
possible in severe renal impairment. Glipizide should be avoided if the patient has both renal and hepatic
impairment. Tolbutamide and gliclazide can be used in renal impairment, but careful monitoring of blood
glucose concentration is essential. Use the lowest dose to adequately control blood glucose.
Thiazolidinediones • Pioglitazone1,2
– ADULT >18 years, 15 mg or 30 mg OD, increased in increments up to 45 mg OD
– ELDERLY, initiate with lowest possible dose and increase gradually); review treatment after 3–6 months
and regularly thereafter
– No dose adjustment is needed in patients with impaired renal function (creatinine clearance >4 mL/min)
– Should not be used in dialysed patients
Note: Dose of concomitant sulfonylurea or insulin may need to be reduced
References:
1. British National Formulary 2015. Available at: https://www.medicinescomplete.com/about/subscribe.htm Website accessed 03.02.15;
2.Takeda UK Ltd. Actos (Pioglitazone) EU SPC 2013.
13
Glucose control therapies in type 2 diabetes and CKD
(3 of 4)
Medication
Recommended use in renal impairment
GLP-1 receptor
agonists/
Mimetics cont.
• Exenatide1
– ADULT >18 years, initially 5 μg twice daily within 1 hour before 2 main meals (at least 6 hours apart),
increased if necessary after at least 1 month to max. 10 μg twice daily
– Standard release injection: use with caution if eGFR 30–50 mL/minute/1.73 m2; avoid if eGFR <30
mL/minute/1.73m2
– Modified release injection: avoid if eGFR <50 mL/minute/1.73 m2
• Lixisenatide1
– ADULT >18 years, initially 10 μg OD within 1 hour before the first meal of the day or the evening meal for
14 days, increased to 20 μg OD thereafter
– Use with caution if eGFR 30–50 mL/minute/1.73 m2
– Avoid if eGFR less than 30 mL/minute/1.73 m2—no information available
• Liraglutide1
– ADULT >18 years, initially 0.6 mg OD, increased after at least 1 week to 1.2 mg OD, further increased if
necessary after an interval of at least 1 week to max. 1.8 mg OD
– Avoid if eGFR less than 60 mL/minute/1.73 m2—limited experience
ALL1: Note: Dose of concomitant sulfonylurea or insulin may need to be reduced
Alpha glucosidase
antagonist
• Acarbose1
– ADULT >18 years, initially 50 mg daily increased to 50 mg 3 times daily, then increased if necessary
after 6–8 weeks to 100 mg 3 times daily; max. 200 mg 3 times daily
– Avoid if eGFR less than 25 mL/minute/1.73 m2
– To counteract possible hypoglycaemia, patients receiving insulin or a sulfonylurea as well as acarbose
need to carry glucose (not sucrose—acarbose interferes with sucrose absorption)
References:
1. British National Formulary 2015. Available at: https://www.medicinescomplete.com/about/subscribe.htm Website accessed 03.02.15.
14
Glucose control therapies in type 2 diabetes and CKD
(4 of 4)
Medication
SGLT-2 inhibitors
Recommended use in renal impairment
• Empagliflozin 1
– ADULT >18 years, 10 mg OD, if necessary and if tolerated, increase to max. 25 mg OD
– ELDERLY >85 years, initiation not recommended
– Avoid if eGFR is persistently <45 mL/minute/1.73 m2
– Avoid initiation if eGFR <60 mL/minute/1.73 m2
– Reduce dose to 10 mg OD if eGFR falls persistently <60 mL/minute/1.73 m 2
• Dapagliflozin 1
– ADULT >18 years, 10 mg OD
– ELDERLY over 75 years, initiation not recommended
– Avoid if eGFR <60 mL/minute/1.73 m2 (ineffective)
• Canagliflozin 1*
– ADULT >18 years, 100 mg OD preferably before breakfast; if necessary and tolerated, increase to 300
mg OD
– Avoid initiation if eGFR <60 mL/minute/1.73 m2
– Avoid in combination with metformin if eGFR <60 mL/minute/1.73 m 2
– Reduce dose to 100 mg OD if eGFR falls persistently <60 mL/minute/1.73m 2 and existing canagliflozin
treatment tolerated
– Avoid if eGFR <45 mL/minute/1.73m2
– Monitor renal function at least twice a year in moderate impairment
ALL1: Dose of concomitant insulin or drugs that stimulate insulin secretion may need to be reduced.
Determine renal function before treatment and before initiation of concomitant drugs that may reduce renal
function, then at least annually thereafter
*Prescribing information is provided at the end of the this section
15
References:
1. British National Formulary 2015. Available at: https://www.medicinescomplete.com/about/subscribe.htm Website accessed 03.02.15.
Insulin in CKD
• Insulin resistance and reduced clearance of insulin can lead to swings in
glycaemic levels1
• Insulin therapy requirements may reduce as kidney function declines due to:
– The effect of reduced kidney function on insulin clearance2,3
– Reduction of gluconeogenesis in the kidney3
– Uraemia-induced anorexia and weight loss3
• There are no evidence-based guidelines or recommendations about which
types of insulin to use or avoid depending on the severity of CKD2
– Some studies suggest avoiding long-acting insulin, whereas others support its use2
• Frequent monitoring is advised2,4
References:
1. Sobngwi E, et al. Diabetes Care 2010;33(7):1409-12. 2. Cavanaugh KL. Clinical Diabetes 2007;25(3):90-97. 3. Iglesias P & Diez JJ. Diabetes, Obesity and Metabolism
2008;10:811–823. 4. National Kidney Foundation KDOQI Clinical Practice Guidelines for Diabetes and CKD: 2012 Update. Available at http://www.kidney.org/sites/default
/files/docs/diabetes-ckd-update-2012.pdf. Website last accessed on 12.11.14
16
Dialysis can effect glycaemic control and the risk of
hypoglycaemic events
• Haemodialysis can affect glycaemic control in the following ways:1
– Improves insulin sensitivity
– Improves insulin clearance
• Insulin requirements may be 25% lower the day after dialysis compared with
the day before.1 Mean blood glucose is lower on dialysis days2
• Inadequate gastrointestinal glucose absorption (due to gastroparesis) can
also negatively influence glycaemic control in patients with diabetes
undergoing dialysis3
• Therefore in patients receiving dialysis there is a clear need to review:
– HbA1c trends4
– Current medication4
– HbA1c levels, with regards to reliability of results5
References:
1. Sobngwi E, et al. Diabetes Care 2010;33(7):1409-12. 2. Kazempour-Ardebili S et al. Diabetes Care 32:1137–1142, 2009.
3. Iglesias P & Diez JJ. Diabetes, Obesity and Metabolism 2008;10:811–823. 4.Cavanaugh KL. Clinical Diabetes 2007;25(3):90-97.
5. Shrishrimal K, et al. Cleveland Clinic Journal of Medicine 2009;76(11):649-655.
17
Management of people with diabetes who require
dialysis should be a collaboration with the renal team
Diabetes teams to remain involved
with care of dialysis patients
• Foot checks, retinal screening,
adjustment of glycaemic
control (insulin)
Specialist members of the renal team
involved in the care of renal patients
receiving dialysis:
Nephrologist
Renal teams to adjust medications
• Anti-hypertensives, diuretics
Renal teams to manage complications
of CKD
• Anaemia, metabolic bone disease
(initiate treatment, prescribe
specialist drugs e.g. intravenous iron
& ESA therapy, Cinacalcet®)
A specialist renal dietician to provide
dietary advice
Renal
Pharmacist
Dietician
THE
RENAL
TEAM
Specialist
Nurses*
Counsellor
Social
Services
rep
*Specialist nurses to manage anaemia, bone management, dialysis
18
When albuminuria is not ‘diabetic’
• Suspect kidney disease other than diabetic nephropathy and consider further
investigation or referral when the albumin:creatinine ratio (ACR) is raised and
ANY of the following apply:1
– There is no significant or progressive retinopathy1
– Blood pressure is particularly high or resistant to treatment1
– The person previously had a documented ACR <3mg/mmol and develops heavy
proteinuria (ACR >100 mg/mmol)1
– Significant haematuria is present1 (exclude infection)
– The eGFR has worsened rapidly1 (≥25% after starting ACEI or 15ml/min/1.73m²
within 12 months2)
– The person is systemically ill1 (exclude acute kidney injury)
References:
1. NICE clinical guideline 87. The management of type 2 diabetes. Issued: May 2009 last modified: July 2014
2. NICE clinical guideline 182. Chronic kidney disease early identification and management of chronic kidney disease in adults in primary and secondary care. July 2014..
19
When to refer a patient to nephrology
NICE referral criteria:
•
GFR <30 ml/min/1.73 m2 (GFR category G4 or G5), with or without diabetes1
•
ACR ≥70 mg/mmol, unless known to be caused by diabetes and already
appropriately treated1
•
ACR ≥30 mg/mmol (ACR category A3), together with haematuria1
•
Sustained decrease in GFR of ≥ 25%, and a change in GFR category or
sustained decrease in GFR of ≥15 mL/min/1.73 m2 within 12 months1 (no
requirement to be on a diuretic)*
•
Hypertension that remains poorly controlled despite the use of at least 4
antihypertensive drugs at therapeutic doses1
•
Known or suspected rare or genetic causes of CKD1
•
Suspected renal artery stenosis1*
Referral may also be indicated if:
•
Suspicion of non-diabetic kidney disease*
•
Advice to manage complications of CKD e.g. anaemia, acidosis1
•
To establish an alternative diagnosis*
*Advice from the advisory board
References:
1. NICE clinical guideline 182. Chronic kidney disease early identification and management of chronic kidney disease in adults in primary and secondary care. July 2014.
20
Section F – summary
• ACE inhibitor or ARB therapy improves outcomes in diabetic kidney
disease
• ACE inhibitors and ARBs should not be prescribed together
• Presence of diabetic kidney disease implies generalised vascular
disease which requires holistic management
• Oral hypoglycaemic therapy needs adjusting in people with diabetic
kidney disease
• Insulin may need adjusting if people with diabetes and kidney disease
are receiving dialysis
• Consider referral to a nephrologist when appropriate
• Work collaboratively with your local renal team
21
Prescribing information
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 studied in
patients with 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. SIDE EFFECTS: Very
common: hypoglycaemia in combination with insulin or sulphonylurea,
vulvovaginal candidiasis. Common: constipation, thirst, nausea, polyuria or
pollakiuria, urinary tract infection, balanitis or balanoposthitis, dyslipidemia,
hematocrit increased.Uncommon: dehydration, postural dizziness, syncope,
hypotension, orthostatic hypotension, rash, urticaria, bone fracture, blood
creatinine increased, blood urea increased, blood potassium increased, blood
phosphate increased.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 anticancer 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, EU/1/13/884/002, pack of 30 tablets: £39.20. Invokana 300
mg film-coated tablets, EU/1/13/884/006, pack of 30 tablets: £49.99.
MARKETING AUTHORISATION HOLDER: Janssen-Cilag International NV,
Turnhoutseweg 30, B-2340 Beerse, Belgium. FURTHER INFORMATION IS
AVAILABLE FROM: Janssen-Cilag Ltd, 50-100 Holmers Farm Way, High
Wycombe, Buckinghamshire HP12 4EG UK. © Janssen-Cilag Ltd 2014
Prescribing information last revised: April 2014. PIVER15112014
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 Ltd on 01494
567447.