March 2015

What’s new in BNF 69?

Enter

A CPPE interactive PDF learning programme

N e x tB a c k

Thank you for downloading this CPPE interactive learning programme. We hope that you will find it a fun way to bring you up to date with the latest changes in the British National Formulary (BNF).

Welcome toWhat’s new inBNF 69?

The Centre for Pharmacy Postgraduate Education (CPPE) offers a wide range of learning opportunities in a variety of formats for pharmacy professionals from all sectors of practice. We are funded by Health Education England to offer continuing professional development for all pharmacists and pharmacy technicians providing NHS services in England. For further information about our learning portfolio, visit: www.cppe.ac.uk

This document uses interactive features that are supported on most mobile devices. If you are using this programme on a PC or laptop, please ensure you are using an up-to-date version of Adobe Reader.

© Copyright Controller HMSO 2015

Learning with CPPE

Contents

3 How to use this learning programme

4 About What’s new in BNF 69?

5 Learning objectives

6 Case studies – introduction

7 Case studies

38

Click on a title to go directly to that section.

Next steps

39 Programme credits

2

NextBack Contents

How to use this learning programmeThis programme uses an interactive PDF format. You can

navigate your way through by using the arrows in the

bottom right corner of each page. Where directed, you

can also navigate to sections by clicking on text or images.

The programme uses case studies and web links to help

you explore the changes in BNF 69. You will need to be

connected to the internet to access the web links. Text that

links to other sections of the programme is in yellow and text

that links to the internet is in blue.

You will be able to type, save and view answers to the case

studies. We would recommend that you keep notes as you go

along as these could be ideal to generate CPD records or to

record evidence for RPS Faculty applications.

3

NextBack Contents

This programme will keep you up to date with significant changes in the BNF that

are relevant to your clinical practice. You will need about 60 minutes to complete

the questions.

Before you start, make sure you have read the section of the BNF listing the key

changes for this edition. If you are using a print version of BNF 69, full details of

changes to this edition are on pages xvii to xviii. The margins of these pages are

marked in blue.

You can access the BNF online through Medicines Complete by clicking on the

image. If you are not already registered, you will need to do so. Click here to

register.

About What’s new in BNF 69?

4

NextBack Contents

Learning objectives

n locate information on changes in the latest BNF

n identify situations in the healthcare setting where the management of a patient is

affected by these changes

n recommend appropriate courses of action based on what you know about a patient

and the latest information in the BNF.

By the end of this learning programme, you should be able to:

5

NextBack Contents

Case studies – introductionThis programme contains ten case studies, each with two parts, to

explore significant changes to the BNF.

In these, there will be space for you to type answers to the questions.

You can save your answers by saving this document to your computer

and you can view our suggested answers by clicking on the Suggested

answer links.

Some of the scenarios are based in primary care and some in

secondary. However, the decisions we ask you to make in each

question will apply to your practice, regardless of your area of work.

6

NextBack Contents

Case studiesThe case studies look at the following areas (click on a title to go straight to that case).

You will be able to return to this menu by clicking the link at the bottom of the page at the end of each question.

7

Drugs and driving

Denosumab-associated osteonecrosisNalmefene

Malaria-prophylaxis Ponatinib

Heart failure

Statins and QRISK2Ivabradine Stroke risk

Varicella-zoster vaccines

NextBack Contents

Drugs and driving8

Paul Behrer is a 46-year-old accounts manager whose

mother died recently. He has been to see his GP as he is

currently finding it very hard to get to sleep and his

insomnia is now affecting his work. His GP has prescribed a

two-week course of temazepam (10 mg at night). He is not

taking any other medicines and is otherwise healthy.

Paul recalls seeing something on the news about a change

in the law saying that he might be prosecuted if he drives

his car while taking these tablets and has come to you for

advice.

Suggested answer

NextBack Contents

9

Don’t forget to save your answers

1. What do the new regulations state with regard to drugs and driving?

ONE

Click to return to the case studies menu

BNF section: Guidance on prescribing – pages 1-4

For further information, read about drugs and driving in the BNF through Medicines Complete.

Access the Medicines and Healthcare products Regulatory Agency (MHRA) advice: Drugs and driving: blood concentration limits to be set for certan controlled drugs in a new legal offence.

Develop your practice by accessing the CPPE Substance use and misuse distance learning programme.

NextBack Contents

10

Don’t forget to save your answers Click to return to the case studies menu

2. What advice can you offer Paul if he decides to take this medicine?

Suggested answer

TWO

BNF section: Guidance on prescribing – pages 1-4

For further information, read about drugs and driving in the BNF through Medicines Complete.

Access MHRA advice: Drugs and driving: blood concentration limits to be set for certain controlled drugs in a new legal offence.

Develop your practice by accessing the CPPE Substance use and misuse distance learning programme.

NextBack Contents

Stroke risk11

Mary Reardon is a 60-year-old retired secretary.

She has come to you as she is concerned about her

risk of having a stroke. Her next door neighbour

has recently suffered one and they have similar

medical problems.

She has hypertension, type 2 diabetes mellitus and

osteoarthritis which limits her mobility. She has

recently been diagnosed with non-valvular atrial

fibrillation and is awaiting electrical cardioversion

to restore sinus rhythm.

NextBack Contents

Don’t forget to save your answers

1. Work out Mary’s risk of stroke and thromboembolism using the CHA2DS2-VASc assessment tool.

12

Click to return to the case studies menu

BNF section: 2.3.1 – pages 93-96

For further information, read about management of arrhythmias in the BNF through Medicines Complete.

Access NICE clinical guideline 180: Atrial fibrillation: the management of atrial fibrillation.

Learn more about stroke by accessing the CPPE Stroke learning@lunch flex programme.

BNF section: 2.3.1 – pages 93-96

For further information, read about management of arrhythmias in the BNF through Medicines Complete.

Access NICE clinical guideline 180: Atrial fibrillation: the management of atrial fibrillation.

Learn more about stroke by accessing the CPPE Stroke learning@lunch flex programme.

NextBack Contents

Don’t forget to save your answers

13

Suggested answer

2. What advice would you give Mary about the need to take further medicines to prevent a stroke?

FOUR

Click to return to the case studies menu

NextBack Contents

Heart failure

14

Stephen Taylor is a 72-year-old gentleman with heart failure due to

left ventricular systolic dysfunction. He is taking bumetanide 5 mg

daily, ramipril 5 mg twice daily and bisoprolol 10 mg daily.

He remains symptomatic and is referred to a specialist who could

consider one of three possible treatment options: an aldosterone

antagonist, hydralazine in combination with a nitrate, or one other

class of drug.

NextBack Contents

Don’t forget to save your answers

1. What other class of drug could the specialist consider initiating for Stephen?

15

Suggested answer

FIVE

Click to return to the case studies menu

BNF section: 2.5.5.1 – pages 119-125

For further information, read about angiotensin-converting enzyme inhibitors, heart failure or angiotensin-II receptor antagonists in the BNF through Medicines Complete.

Access NICE clinical guideline 108: Chronic heart failure: management of chronic heart failure in adults in primaryand secondary care.

Read the MHRA advice: Combination use of medicines from different classes of renin-angiotensin system blocking agents: risk of hyperkalaemia, hypotension, and impaired renal function – new warnings.

Access CPPE’s Heart failure learning@lunch programme to develop a better understanding of the role of the healthcare team in supporting patients with heart failure.

BNF section: 2.5.5.1 – pages 119-125

For further information, read about angiotensin-converting enzyme inhibitors, heart failure, angiotensin-II receptor antagonists and candesartan cilexetil in the BNF through Medicines Complete.

Access NICE clinical guideline 108: Chronic heart failure: management of chronic heart failure in adults in primary and secondary care.

Read the MHRA advice: Combination use of medicines from different classes of renin-angiotensin system blocking agents: risk of hyperkalaemia, hypotension, and impaired renal function – new warnings.

Access CPPE’s Heart failure learning@lunch programme to develop a better understanding of the role of the healthcare team in supporting patients with heart failure. NextBack Contents

Don’t forget to save your answers

2. Following careful consideration, the specialist decides to initiate candesartan 4 mg daily in

addition to Stephen’s current medicines, with a plan to gradually titrate the dose upwards every

three weeks. What monitoring should be conducted while Stephen is taking these medicines?

16

Suggested answer

FIVE

Click to return to the case studies menu

NextBack Contents

Ivabradine

17

Brenda Hill, a 76-year-old lady, presents complaining of dizziness and

fatigue. She has a history of chronic heart failure and asthma. She lives

on her own and is worried she is going to have a fall. She seems very

anxious about her symptoms.

Current medicines

n Furosemide 40 mg each morning

n Spironolactone 25 mg each morning

n Ivabradine 7.5 mg twice daily (increased from 5 mg twice daily two

weeks ago)

n Atorvastatin 20 mg daily

n Salbutamol 100 micrograms one to two puffs when required

n Seretide 250 Evohaler two puffs twice a day

Brenda’s resting pulse is 45 beats per minute (bpm) and her blood

pressure is 102/65 mmHg. All other investigations are normal.

Suggested answer

NextBack Contents

Don’t forget to save your answers

1. What is the most likely cause for Brenda’s symptoms and how should these be managed?

18

Click to return to the case studies menu

BNF section: 2.6.3 – pages 139-141

For further information, read about ivabradine in the BNF through Medicines Complete.

Access the following MHRA advice:n Ivabradine (Procoralan) in the symptomatic treatment of angina: risk of cardiac side-effectsn Ivabradine: carefully monitor for bradycardia

BNF section: 2.6.3 – pages 139-141

For further information, read about prescribing for the elderly (manifestations of ageing and adverse reactions) in the BNF through Medicines Complete.

Access NICE clinical guideline 161: Falls: assessment and prevention of falls in older people.NextBack Contents

19

Suggested answer

2. Brenda’s symptoms resolve following the dose reduction. However, her daughter Sally reports

that she is now afraid of falling. What advice would you offer?

Don’t forget to save your answers Click to return to the case studies menu

Statins and QRISK2Sanjeev Gupta is a 55-year-old male concerned about his

chances of having a heart attack. His father had angina in

his late 50s when the family was still living in India. At a

recent GP appointment Sanjeev was advised that he

needs to start a statin.

You offer to help Sanjeev work out his QRISK2 score.

Sanjeev tells you that at his recent GP appointment he was

told his BMI is 30 kg/m2 (height 180 cm and weight 97 kg)

and his cholesterol/HDL ratio is 5. He isn’t a smoker and

doesn’t have any past medical or medicines history.

NextBack Contents

20

Suggested answer

NextBack Contents

Don’t forget to save your answers

1. Using the QRISK2 tool, calculate Sanjeev’s risk of having a heart attack or stroke in the next ten

years. Which statin and dose would you recommend for Sanjeev?

21

Click to return to the case studies menu

BNF section: 2.12 – pages 172-182

For further information, read about lipid-regulating drugs in the BNF through Medicines Complete.

Access the QRISK2 risk calculator.

Read NICE clinical guideline 181: Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease.

To extend your learning, access the NICE e-learning tool on lipid modification and the CPPE e-learning programmeon vascular risk and the NHS Health Check programme.

BNF section: 2.12 – pages 172-182

For further information, read about lipid-regulating drugs in the BNF through Medicines Complete.

Access NICE clinical guideline 181: Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease.

To extend your learning, access the NICE e-learning tool on lipid modification and the CPPE e-learning programmeon vascular risk and the NHS Health Check programme.

Suggested answer

2. What are Sanjeev’s potential modifiable risk factors for CVD?

22

NextBack Contents

Don’t forget to save your answers Click to return to the case studies menu

NextBack Contents

Nalmefene

Helen Bach is a 45-year-old marketing executive who has

come to see you to discuss her alcohol consumption. She

does not see herself as “an alcoholic” as she only drinks

in the evenings and does not experience any withdrawal

symptoms during the day. She tells you that on average she

consumes a bottle of wine daily but sometimes has a little

more at the weekend.

Her current employment means that she attends a number

of evening functions where alcohol is freely available. She

does not want to or feel that she can immediately stop

drinking alcohol, but recognises a definite need for better

control of her intake. She does not take any medicines.

She has recently confided in a friend about her worries

with regard to her alcohol intake. Her friend has told her

about a new drug that she has read about called

nalmefene.

23

Suggested answer

NextBack Contents

Don’t forget to save your answers

1. Would nalmefene be a suitable option for Helen to try?

24

Click to return to the case studies menu

BNF section: 4.10.1 – pages 338-341

For further information, read about nalmefene and alcohol dependence in the BNF through Medicines Complete.

Access NICE technology appraisal 325: Nalmefene for reducing alcohol consumption in people with alcohol dependence.

CPPE’s Alcohol misuse: support and advice from the pharmacy team distance learning programme is available to extend your learning as a whole pharmacy team.

BNF section: 4.10.1 – pages 338-341

For further information, read about nalmefene and alcohol dependence in the BNF through Medicines Complete.

Access NICE technology appraisal 325: Nalmefene for reducing alcohol consumption in people with alcohol dependence.

CPPE’s Alcohol misuse: support and advice from the pharmacy team distance learning programme is available to extend your learning as a whole pharmacy team.

Suggested answer

2. What cautions and non-drug treatment should be considered if Helen is prescribed nalmefene?

25

NextBack Contents

Don’t forget to save your answers Click to return to the case studies menu

Malaria prophylaxis

Jay Mistry is a 40-year-old gentleman who is planning a

holiday to Andhra Pradesh in India with his 5-year-old

daughter Ana. They leave in four weeks. They are going

to be staying with their family in the Vishakhapatnam

district and will be staying for two months. Neither Jay

nor Ana have any pre-existing medical conditions and

are generally fit and well.

Jay would like to discuss with you his options regarding

malaria prophylaxis. He doesn’t think he needs any

malaria prophylaxis as he has been before and he is not

sure whether his daughter is old enough to take malaria

prophylaxis. She weighs 18 kg.

NextBack Contents

26

NextBack Contents

27

Don’t forget to save your answers Click to return to the case studies menu

BNF section: 5.4.1 – pages 443-458

For further information, read about prophylaxis against malaria, specific recommendations, proguanil hydrochloride with atovaquone, doxycycline and mefloquine in the BNF through Medicines Complete.

Access CPPE’s e-learning programme on travel health to develop your understanding of the health needs of travellers.

Suggested answer

1. Would you recommend malaria prophylaxis to Jay and Ana and what options (including doses

and length of treatment) do they have?

NextBack Contents

28

Don’t forget to save your answers Click to return to the case studies menu

BNF section: 5.4.1 – pages 443-458

For further information, read about prophylaxis against malaria and specific recommendations in the BNF through Medicines Complete.

Access CPPE’s e-learning programme on travel health to develop your understanding of the health needs of travellers.

2. What other advice can you give Jay about his trip to India?

NextBack Contents

Denosumab-associated osteonecrosis29

Jayne Gibson is a 60-year-old lady with a five-year history

of osteoporosis. Last year she fractured her hip and since

then she has tried various bisphosphonates but has been

unable to tolerate the gastrointestinal side-effects

associated with taking them. Jayne is a smoker but

otherwise fit and well with no medical history and resents

having to take these tablets.

As Jayne has been unable to tolerate bisphosphonates she

is now eligible to be treated with denosumab but is

concerned about the potential side-effects. Jayne is

particularly worried about the risks of osteonecrosis of the

jaw (ONJ) and hypocalcaemia associated with denosumab.

1. How would you advise Jayne on reducing her risk of ONJ and recognising signs of hypocalcaemia?

NextBack Contents

30

Don’t forget to save your answers Click to return to the case studies menu

BNF section: 6.6.2 – pages 528-530

For further information, read about denosumab in the BNF through Medicines Complete.

Access MHRA advice: Denosumab 60 mg (Prolia).

BNF section: 6.6.2 – pages 528-530

For further information, read about denosumab in the BNF through Medicines Complete.

Access MHRA advice: Denosumab 60 mg (Prolia).

2. What monitoring can Jayne expect for ONJ and hypocalcaemia associated with her denosumab

therapy?

31

NextBack Contents

Don’t forget to save your answers Click to return to the case studies menu

PonatinibSarah Brown is a 30-year-old woman suffering from

recurrent ear infections, for which her prescriber has given

her antibiotics. She has also previously complained of

various other symptoms: tiredness, weight loss and

sweating more than usual, particularly at night. After some

blood tests she was diagnosed with chronic myeloid

leukaemia (CML).

She is currently taking clarithromycin for her recurrent ear

infection.

Her consultant decides that she should be prescribed

ponatinib for her CML which is diagnosed as in the chronic

phase.

NextBack Contents

32

1. What dose of ponatinib should be prescribed for Sarah and what monitoring is required?

NextBack Contents

33

Don’t forget to save your answers Click to return to the case studies menu

BNF section: 8.1.5 – pages 606-621

For further information, read about protein kinase inhibitors and ponatinib in the BNF through Medicines Complete.

Access MHRA advice: Ponatinib (Iclusig): risk of vascular occlusive events.

To learn more about cancers and providing advice to patients presenting with signs and symptoms of common cancers, you can attend a CPPE Cancer awareness workshop or access the Cancer in community pharmacies, raising public awareness e-learning programme.

BNF section: 8.1.5 – pages 606-621

For further information, read about protein kinase inhibitors and ponatinib in the BNF through Medicines Complete.

Access MHRA advice: Ponatinib (Iclusig): risk of vascular occlusive events.

To learn more about cancers and providing advice to patients presenting with signs and symptoms of common cancers, you can attend a CPPE Cancer awareness workshop or access Cancer in community pharmacies, raising public awareness e-learning programme.

2. What advice should you give Sarah about contraception?

NextBack Contents

34

Don’t forget to save your answers Click to return to the case studies menu

Varicella–zoster vaccinesAva Stempit is a 79-year-old lady living alone in her own

home. She suffers with asthma and high cholesterol.

Current medicines

n Ventolin Evohaler 100 micrograms one to two puffs when required

n Clenil Modulite inhaler 200 micrograms two puffs twice daily

n Atorvastatin 20 mg once daily

Ava has seen a poster display in her local surgery about

shingles. She has grandchildren and fears she might catch it from

them if they get chickenpox. The poster states that a vaccine is

available under the NHS England shingles (catch-up) vaccination

programme. Ava asks you for this vaccine. She has never had

chickenpox or shingles.

NextBack Contents

35

1. Would Ava qualify for a varicella–zoster vaccine under the 2014-2015 catch-up programme?

NextBack Contents

36

Don’t forget to save your answers Click to return to the case studies menu

BNF section: 14.4 – pages 865-866

For further information, read about varicella–zoster vaccines in the BNF through Medicines Complete.

Why not download CPPE’s Immunisation in pharmacies: developing your service distance learning to learn moreabout providing this service.

BNF section: 14.4 – pages 865-866

For further information, read about varicella–zoster vaccines and active immunity in the BNF through Medicines Complete.

Why not download CPPE’s Immunisation in pharmacies: developing your service distance learning to learn more about providing this service.

2. Ava has recently had a course of oral prednisolone at a dose of 40 mg daily for one week for

her asthma. Should her clinician give her the vaccine?

NextBack Contents

37

Don’t forget to save your answers Click to return to the case studies menu

NextBack Contents

Next stepsNow that you have completed the case studies, what’s next?

You might like to:

n revisit the learning objectives. Are you confident that you have

achieved these?

n tackle the reflective essay that you can download from your CPPE

learning record

n complete a CPD entry or RPS Faculty entry

n email CPPE with any feedback you may have on your learning

experience

n take the BNF 69-themed CPPE e-challenge (issue 83).

We hope that you have enjoyed your learning. Come back for more learning when

we publish What’s new in BNF 70? later this year.

38

Back Contents

CreditsCPPE programme manager

Caroline Barraclough, regional manager, East Midlands

Authors

Beth Carney, prescribing advisor and medicines management lead,

Rushcliffe CCG

Jo Clarke, tutor, CPPE

Imran Jawaid, sessional GP, Royal Tunbridge Wells, Kent

Neil Powell, antibiotics and HIV pharmacist, Royal Cornwall Hospital

Kevin Ratcliffe, consultant pharmacist, Birmingham and Solihull

Mental Health Trust

Sharon Warren, senior lecturer, Keele University

Editors

Jessica Forrest, projects team content manager, BNF Publications

Terri Lucas, assistant editor, CPPE

Disclaimer

We have developed this learning programme to support your

practice in this topic area. We recommend that you use it in

combination with other established reference sources. If you are

using it significantly after the date of initial publication, then you

should refer to current published evidence. CPPE does not accept

responsibility for any errors or omissions.

Brand names and trademarks

CPPE acknowledges the following brand names and registered

trademarks mentioned throughout this programme: Clenil

Modulite®, Evohalor®, Iclusig®, Malarone®, Procoralan®,

Prolia®, QRISK®2, Seretide® and Ventolin®.

Acknowledgements

CPPE acknowledges the support of the British National

Formulary for allowing us to use links and text from their

publication.

A special thank you to Zara Jones for her patient participation

with this programme.

Production

Gemini West, 25 Hockeys Lane, Fishponds, Bristol, BS16 3HH

T: 0117 965 5252. www.gemini-west.co.uk

Published in March 2015 by the Centre for Pharmacy

Postgraduate Education, Manchester Pharmacy School, The

University of Manchester, Oxford Road, Manchester M13 9PT.

www.cppe.ac.uk

Next

39

Contacting CPPEFor information on your orders or bookings, or any general enquiries, please contact us by email, telephone or post. A member of our customer services team will be happy to help you with your enquiry.

Email info@cppe.ac.uk

Telephone 0161 778 4000

By post Centre for Pharmacy Postgraduate Education (CPPE)Manchester Pharmacy School1st Floor, Stopford BuildingThe University of ManchesterOxford RoadManchester M13 9PT

For information on all our programmes and events: visit our website www.cppe.ac.uk

Share your learning experience with us:email us at feedback@cppe.ac.uk

Developed by:Funded by:

Suggested answers

Contents

Drugs and driving

Return to case study

1. What do the new regulations state with regard to drugs and driving?

A new offence of driving, attempting to drive, or being in charge of a vehicle with certain controlled drugs above specified limits in the blood came into force on 2 March 2015. These drugs include some prescribed medicines such as temazepam. Anyone found to have any of the drugs above specified limits in their blood is guilty of an offence, whether their driving is impaired or not. A preliminary, non-specific roadside test may be used to detect if an individual has any of the drugs in their body. To identify the particular drug taken and quantify blood levels, a blood sample will be taken at a police station and sent for forensic analysis.

The legislation provides a statutory medical defence for people taking the drugs for medical reasons if their driving was not impaired. The conditions of the medical defence state that the individual is not guilty of an offence if the medicine was prescribed, supplied, or sold to treat a medical or dental problem and it was taken according to the instructions given by the prescriber or the information provided with the medicine.

The individual may need to provide written evidence to satisfy the points above (eg, the tear-off section of a prescription or the medicine’s patient information leaflet).

It should be noted that if the individual’s driving is impaired they can be found guilty of an offence under the current law, which has no statutory medical defence and will not change.

Drugs and driving

2. What advice can you offer Paul if he decides to take this medicine?

It should be noted that any condition that requires medicinal treatment may itself pose a risk to driving ability if left untreated.

You can offer Paul the following advice:n Continue taking your medicine as prescribed.n Check the leaflet that comes with your medicine for information on how it may

affect your driving ability.n It is against the law to drive if your driving ability is impaired by this medicine.n Do not drive while taking this medicine until you know how it affects you

(especially just after starting or changing the dose of the medicine).n Do not drive if you feel sleepy, dizzy, unable to concentrate or make decisions, or

if you have blurred or double vision.n The risk of driving impairment is increased if the medicine is taken with alcohol,

so you should avoid drinking alcohol while taking this medicine.

The MHRA has issued a patient leaflet about the new law on driving while taking certain drugs. It may be helpful for Paul to have a copy of this for further information.

Stroke risk

1. Work out Mary’s risk of stroke and thromboembolism using the CHA2DS2-VASc assessment tool.

Mary has a score of 3 which indicates a high risk of stroke and thromboembolism.

The CHA2DS2-VASc assessment tool scores points for each of the following risk factors. The maximum score is 9.

Factor Score

Age Under 65 years 0 65-74 years 1 75 years or over 2Gender Male 0 Female 1Congestive heart failure history No 0 Yes 1Hypertension history No 0 Yes 1Stroke, transient ischaemic No 0attack or thromboembolism history Yes 2Vascular disease history No 0 Yes 1Diabetes mellitus No 0 Yes 1

n A score of 0 indicates a low risk of stroke.n A score of 1 indicates a low-moderate risk of stroke.n A score or 2 or more indicates a moderate-high risk of stroke.

Stroke risk

2. What advice would you give Mary about the need to take further medicines to prevent a stroke?

Mary has a CHA2DS2-VASc score of 3 which means that anticoagulation treatment for the prevention of stroke would be indicated. Guidance also states that before electrical cardioversion is attempted the patient must be fully anticoagulated for at least three weeks.

Discuss the options for anticoagulation medicine with Mary and base the choice on her clinical features and preferences. Her options for anticoagulation include a vitamin K antagonist (warfarin), apixaban or rivaroxaban.

The HAS-BLED calculator can be used to assess bleeding risk prior to and during anticoagulation for patients with atrial fibrillation. Based on Mary’s comorbidities, consider how her current medicines could increase her risk of bleeding (eg, she may be taking NSAIDs for her osteoarthritis).

All men with a CHA2DS2-VASc score of 1 or more and women with a score of 2 or more should be considered for anticoagulation.

NICE does not recommend aspirin as monotherapy solely for stroke prevention for patients with atrial fibrillation.

Further informationNICE technology appraisal 256: Rivaroxaban for the prevention of stroke and systemic embolism in people with atrial fibrillation. 2012.

NICE technology appraisal 275: Apixaban for preventing stroke and systemic embolism in people with nonvalvular atrial fibrillation. 2013.

American College of Cardiology. Atrial fibrillation toolkit.

Return to case study

Heart failure

1. What other class of drug could the specialist consider initiating for Stephen?

A potential third option for Stephen could be an angiotensin-II receptor antagonist.

A recent EU review concluded that dual therapy with an angiotensin-converting enzyme (ACE) inhibitor plus an angiotensin-II receptor antagonist is not recommended. However, there is some evidence that the benefits of combination use may outweigh the risks in a selected group of patients with heart failure for whom other treatments are unsuitable.

The NICE clinical guideline on chronic heart failure recommends that, following specialist advice, the addition of an angiotensin-II receptor antagonist licensed for heart failure could be considered for patients who remain symptomatic despite optimal therapy with an ACE inhibitor and a beta-blocker. Other alternative options include the addition of an aldosterone antagonist licensed for heart failure or hydralazine in combination with a nitrate.

The triple combination of an ACE inhibitor, angiotensin-II receptor antagonist, and a mineralocorticoid receptor antagonist or other potassium-sparing diuretic is not recommended.

2. Following careful consideration, the specialist decides to initiate candesartan 4 mg daily in addition to Stephen’s current medicines, with a plan to gradually titrate the dose upwards every three weeks. What monitoring should be conducted while Stephen is taking these medicines?

Patients taking an angiotensin-II receptor antagonist such as candesartan should have plasma-potassium concentrations monitored, particularly if they are elderly or have renal impairment.

Patients taking ACE inhibitors should have renal function and electrolytes checked and monitored during treatment (especially when increasing the dose).

Patients taking combination therapy of an ACE inhibitor and an angiotensin-II receptor antagonist should be under specialist review with close monitoring of blood pressure, renal function, and electrolytes (particularly potassium) to minimise the risk of deterioration in renal function and hyperkalaemia.

Monitoring should be considered at the start of treatment, then monthly and also after any change in dose or during intercurrent illness.

Return to case study

Heart failure

Return to case study

1. What is the most likely cause for Brenda’s symptoms and how should these be managed?

Brenda’s symptoms are most likely due to bradycardia and hypotension which could be a result of her ivabradine dose increase two weeks ago.

Brenda should have her ivabradine dose reduced to 5 mg twice daily and she should be monitored closely following her dose reduction. If her heart rate remains below 50 bpm or her symptoms persist, her ivabradine dose should be reduced further to 2.5 mg twice daily. If reducing the dose does not cause her heart rate to increase or resolve her symptoms, ivabradine should be withdrawn and discontinued.

Ivabradine

Return to case study

2. Brenda’s symptoms resolve following the dose reduction. However, her daughter Sally reports that she is now afraid of falling. What advice would you offer?

You should offer general advice on minimising the risk of having a fall. Sally can minimise hazards at Brenda’s home by removing rugs and making sure wires are out of the way. She should encourage her mother to have regular eye tests and wear well-fitting footwear, including slippers, that provide support. She could also suggest that Brenda uses hand rails or walking aids.

Exercise is one of the most important preventative measures in order to maintain strength and balance. Brenda may not be doing as much exercise due to her age and possibly her respiratory condition. You could enquire about when Brenda last had an asthma review. You should signpost Sally and Brenda to appropriate local services, eg, Falls Prevention Service.

Explain to Sally that the symptoms her mother previously experienced are the most common side-effects of ivabradine and if her mother experiences these again she should seek medical advice. Other side-effects seen with ivabradine are headaches and visual disturbances (blurred vision and phosphenes).

To reinforce the advice given, you should offer written information for Sally to take away and share with her mother. This information should include the measures they can take to prevent falls, where they can seek further advice and assistance, and how to cope if Brenda does have a fall, including how to summon help and avoid a long lie.

Ivabradine

Return to case study

1. Using the QRISK2 tool, calculate Sanjeev’s risk of having a heart attack or stroke in the next ten years. Which statin and dose would you recommend for Sanjeev?

Sanjeev’s QRISK2 score reveals that his risk of having a heart attack or stroke in the next ten years is 16.6 percent. NICE recommends that patients with a cardiovascular disease (CVD) risk over 10 percent be considered for statin therapy after discussing the benefits of lifestyle modification and optimising the management of all other modifiable CVD risk factors where possible.

There are many different statins available. NICE guidelines recommend a statin of high-intensity and low acquisition cost.

For the primary prevention of cardiovascular disease in people with a 10 percent or greater ten year risk of developing CVD, atorvastatin prescribed at a dose of 20 mg once daily is recommended.

As Sanjeev has a 16.6 percent chance of developing CVD, atorvastatin 20 mg daily would be recommended.

Total cholesterol, HDL-cholesterol and non-HDL cholesterol concentrations should be checked three months after starting treatment.

Statins and QRISK2

Return to case study

2. What are Sanjeev’s potential modifiable risk factors for CVD?

NICE recommends discussing the benefits of lifestyle modification and optimisation of the management of all other modifiable CVD risk factors where possible before offering statin treatment for primary prevention of CVD.

These potential lifestyle modifications include:n eating a cardio-protective dietn ensuring adequate physical activityn weight managementn reducing alcohol consumption.

You should ask Sanjeev about his lifestyle to identify all potential modifiable lifestyle factors. From what we know already, his weight may potentially be modified to reduce his CVD risk. Sanjeev may need support to change his lifestyle in order to lose weight. You can help him, for example, by referring him to an exercise referral scheme.

Statins and QRISK2

1. Would nalmefene be a suitable option for Helen to try?

Nalmefene is an opioid receptor modulator, which exhibits antagonist activity at the mu and delta opioid receptors, and partial agonist activity at the kappa opioid receptors. Nalmefene has a marketing authorisation in the UK for the reduction of alcohol consumption in adult patients with alcohol dependence who have a high drinking risk level without physical withdrawal symptoms and who do not require immediate detoxification.

The summary of product characteristics states that a high drinking risk level is defined as alcohol consumption of more than 60 g (7.5 units) per day for men and more than 40 g (5 units) per day for women, according to the World Health Organization’s drinking risk levels.

Helen has disclosed that she is drinking at a high drinking risk level, does not have physical withdrawal symptoms and does not currently wish to stop drinking completely. Helen also has insight in that she recognises that a problem exists and appears motivated to address it. As such, nalmefene is a potential option to support her in doing this.

Nalmefene

Return to case study

2. What cautions and non-drug treatment should be considered if Helen is prescribed nalmefene?

Helen’s clinical status, level and pattern of alcohol consumption, and presence of dependence should be evaluated before she starts treatment with nalmefene. Nalmefene should only be prescribed for patients who continue to have a high drinking risk level two weeks after the initial assessment.

In addition, nalmefene should only be prescribed in conjunction with continuous psychosocial support focused on treatment adherence and reducing alcohol consumption.

During treatment, Helen should be monitored regularly and the need for continued treatment assessed. Caution is advised if treatment is continued for more than one year.

Nalmefene

Return to case study

1. Would you recommend malaria prophylaxis to Jay and Ana and what options (including doses and length of treatment) do they have?

The recommended regimens for prophylaxis against malaria have been updated. It is important to check individual requests at the time of asking; however, if they are travelling in a few months’ time, advise them to also check prophylaxis recommendations closer to their intended travel date (eg, three weeks prior to travelling) in case the recommendations have changed.

Jay and Ana should have malarial prophylaxis as the risk of malaria is high in this area. The recommended regimens for prophylaxis against malaria in the Vishakhapatnam district of Andhra Pradesh (India) are Malarone, doxycycline or mefloquine.

MalaroneStart one to two days before entering endemic area and continue for one week after leaving. May be crushed and mixed with food or milky drink just before administration.n Jay (adult) – one Malarone tablet once dailyn Ana (11-21 kg) – one Malarone paediatric tablet once daily

DoxycyclineStart one to two days before entering endemic area and continue for four weeks after leaving.n Jay (adult) – 100 mg once dailyn Ana – not recommended as she is under 12 years old

Malaria prophylaxis

Return to case study

MefloquineStart two to three weeks before entering endemic area and continue for four weeks after leaving. May be crushed and mixed with food such as jam or honey just before administration.n Jay (adult) – 250 mg once a weekn Ana (16-25 kg) – 125 mg once a week

Jay would need to understand the advantages and disadvantages of each option before making a decision on which would be best for him and for Ana.

You need to discuss side-effects, particularly the potentially serious neuropsychiatric reactions possible with mefloquine, as well as its potential to cause dizziness or a disturbed sense of balance affecting the performance of skilled tasks (eg, driving).

Jay needs to consider the cost and duration of treatment. You must tell Jay how to obtain the antimalarials and that they are not available on prescription by the NHS.

2. What other advice can you give Jay about his trip to India?

Advice about malarian Antimalarials and preventing mosquito bites do not eliminate the risk of contracting malaria (although

they do significantly reduce the risk).n Advise Jay on the importance of taking the antimalarial medicines regularly and as prescribed.n If malaria is suspected, medical attention must be sought as soon as possible.n Advise Jay that if any illness develops, particularly within three months of their return, they should go

immediately to a doctor and specifically mention their exposure to malaria.

Advice about avoiding mosquito bitesn Advise Jay and Ana to cover up with clothing where practical and to apply diethyltoluamide (DEET)-based

insect repellents to all exposed areas of the body.n They should use mosquito nets while in bed and spray insecticides in the bedroom prior to sleep.n Using air conditioning or fans to cool the room will reduce mosquito activity.

Travel immunisationsn It would also be advisable to check whether Jay and Ana require any travel immunisations and advise

them on how to obtain these.

Malaria prophylaxis

1. How would you advise Jayne on reducing her risk of ONJ and recognising signs of hypocalcaemia?

Smoking is one of the risk factors for ONJ and as Jayne is a smoker she should be advised on smoking cessation to reduce her risk.

Other potential risk factors Jayne should be made aware of include old age, poor oral hygiene, invasive dental procedures (including tooth extractions, dental implants, oral surgery), comorbidity (including dental disease, anaemia, coagulopathy, infection), advanced cancer, previous treatment with bisphosphonates, and concomitant treatments (including chemotherapy, antiangiogenic biologics, corticosteroids, and radiotherapy to head and neck).

As Jayne has a number of risk factors for ONJ (old age, smoker, previous treatment with bisphosphonates), in order to reduce her risk of ONJ she should:n have a dental examination and appropriate preventative dentistryn be advised to maintain good oral hygiene, receive routine dental check-ups, and immediately report any

oral symptoms such as dental mobility, pain or swelling to a doctor and dentist.

Denosumab is also associated with a risk of hypocalcaemia. This risk increases with the degree of renal impairment. Hypocalcaemia usually occurs in the first weeks of denosumab treatment, but it can also occur later in treatment. Jayne should also be advised to report symptoms of hypocalcaemia, such as muscle spasms, twitches, cramps, or numbness or tingling in the fingers, toes, or around the mouth, to her doctor.

Denosumab-associated osteonecrosis

2. What monitoring can Jayne expect for ONJ and hypocalcaemia associated with her denosumab therapy?

In order to prevent ONJ Jayne will be reviewed for risk factors before starting treatment. A dental examination and appropriate preventative dentistry is also recommended. Once her treatment has started she will need to receive routine dental check-ups.

Jayne will also have her plasma-calcium concentration monitored:n before each dosen within two weeks after the initial dose if she has other risk factors for hypocalcaemia (eg, severe renal

impairment, creatinine clearance less than 30 mL/minute)n if suspected symptoms of hypocalcaemia occur.

Denosumab-associated osteonecrosis

1. What dose of ponatinib should be prescribed for Sarah and what monitoring is required?

Sarah will need an initial dose of 30 mg once daily.

Most adults would receive 45 mg once daily; however, the dose should be reduced initially to 30 mg once daily with concomitant use of potent inhibitors of cytochrome P450 enzyme CYP3A4 (eg, clarithromycin, indinavir, itraconazole, ritonavir, saquinavir, telithromycin or voriconazole). Sarah is currently taking clarithromycin, so her starting dose should be reduced.

Sarah should receive the following monitoring while taking ponatinib:n monitor serum lipase every two weeks for the first two months and periodically thereafter for all patients

(withhold treatment if lipase elevated and abdominal symptoms occur)n monitor full blood count every two weeks for the first three months and then monthly thereafter or as

clinically indicatedn monitor liver function periodically.

There is also risk of serious vascular occlusive events with ponatinib. Recent MHRA advice indicates that the risk of blood vessel blockage is likely to be dose-dependent. Sarah should have her blood pressure checked regularly and be monitored for signs of heart problems. She should be monitored for vascular occlusion or thromboembolism (interrupt treatment immediately if this occurs).

Ponatinib should be stopped if a complete haematologic response has not occurred within three months of treatment.

Ponatinib

2. What advice should you give Sarah about contraception?

Ponatinib, like other cytotoxic drugs, is teratogenic and shouldn’t be given during pregnancy, especially in the first trimester.

The possibility of pregnancy should be excluded before treatment is initiated. Sarah should be counselled to ensure she uses full contraception at all times during treatment and for the appropriate duration after treatment has finished. This would be discussed and advised by the prescriber on an individual basis.

The effectiveness of hormonal contraception when taken with ponatinib is unknown and therefore alternative or additional methods of contraception should be used to prevent pregnancy during treatment.

Ponatinib

1. Would Ava qualify for a varicella–zoster vaccine under the 2014-2015 catch-up programme?

Under the 2014-2015 catch-up programme, the varicella-zoster vaccine will be offered to people who were 78 or 79 years of age on 1 September 2014.

Ava is currently 79 years old and therefore fits the criteria. The varicella-zoster vaccine is a live vaccine and a single dose is likely to give her protection for up to seven years.

She should contact her local surgery to make an appointment for the vaccination. She can have the vaccination at any time of the year but it may be convenient to have it at the same time as her annual flu vaccination.

Reassure Ava that she can’t catch shingles from her grandchildren as it results from a reawakening of the chickenpox virus already in the body. Shingles tends to be seen more commonly in older people as advancing age, medicines, stress and illness can allow the chickenpox virus to become reawakened.

Advise Ava that although she has not had chickenpox she should get the vaccination. There is a risk that she might have had chickenpox without knowing it, as some people can have chickenpox without displaying any of the typical symptoms.

Further informationNHS Employers, General Practitioners Committee, NHS England. Vaccination and immunisation programmes 2014/15 – guidance and audit requirements. NHS Employers. 2014.

NHS Choices. Shingles vaccine: frequently asked questions.

Varicella–zoster vaccines

2. Ava has recently had a course of oral prednisolone at a dose of 40 mg daily for one week for her asthma. Should her clinician give her the vaccine?

Varicella-zoster vaccine is a live vaccine and such vaccines should be avoided in the immunocompromised. As Ava has recently had a course of oral steroids she should not receive the vaccine until at least three months after finishing her course of treatment.

Immune response to vaccines may be reduced in immunocompromised patients and there is also a risk of generalised infection with live vaccines. Severely immunocompromised patients should not be given live vaccines (including those with severe primary immunodeficiency). Specialist advice should be sought for those being treated with high doses of corticosteroids (dose equivalents of prednisolone: adults – at least 40 mg daily for more than one week; children – 2 mg/kg daily for at least one week or 1 mg/kg daily for one month), or other immunosuppressive drugs, and those being treated for malignant conditions with chemotherapy or generalised radiotherapy.

Varicella–zoster vaccines