Download 2: Cardiovascular system - Gateshead Health NHS Foundation Trust

2: Cardiovascular system
Please select a topic:
2.1 Positive inotropic drugs
2.2 Diuretics
2.3 Anti-arrhythmic drugs
2.4 Beta-adrenoceptor blocking drugs
2.5 Drugs affecting the renin-angiotensin
2.6 Nitrates, calcium-channel blockers, and
system and some other antihypertensive
other anti-antianginal drugs
drugs
2.7 Sympathomimetics
2.8 Anticoagulants and protamine
2.9 Antiplatelet drugs
2.10 Myocardial infarction and fibrinolysis
2.11 Antifibrinolytic drugs and
2.12 Lipid-regulating drugs
haemostatics
2.13 Local sclerosants
Changes to the Formulary since previous version
(17.3.2014)
Section
Change
Reason for change
2.5
ADDED: Combination use of
medicines from different
classes of renin-angiotensin
system blocking agents: risk of
hyperkalaemia, hypotension,
and impaired renal function—
new warnings
MHRA Drug Safety Update
2.6
ADDED: Ivabradine: emerging
clinical trial evidence of
increased cardiovascular risk—
carefully monitor for
bradycardia
MHRA Drug Safety Update
2.2
ADDED: Metolazone
Gateshead Medicines
Management Committee approval
2.2
ADDED: Torasemide
Gateshead Medicines
Management Committee approval
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 1 of 31
Date: 11.7.2014
2.1 Positive inotropic drugs

Digoxin 62.5, 125, 250 microgram tablets

Digoxin 250 micrograms/5ml elixir

Digoxin 250 micrograms/ml injection

Enoxamine 100mg/20ml injection (Emergency Drug Cupboard only)

Digifab injection (restricted)
Dose
- Digoxin tablets 62.5micrograms, 125micrograms, 250micrograms; elixir 50micrograms/mL:
rapid digitalisation, 1-1.5mg in divided doses over 24 hours; less urgent digitalisation, 250500micrograms daily (higher dose may be divided). Maintenance, 62.5-500micrograms daily.
- Digoxin injection 250micrograms/mL: according to local guidance.
- Enoxamine injection 100mg/20ml: see BNF
- Digifab injection: see product literature
Prescribing notes

Digoxin is indicated for rate control in atrial fibrillation and symptomatic heart failure; it has
no role in the prophylaxis of atrial fibrillation.

For rapid rate control in atrial fibrillation, a loading dose of digoxin may be given
intravenously or orally.

Regular measurements of plasma digoxin concentrations are not usually required except to
confirm toxic or sub-therapeutic levels, or to check compliance.

Digoxin should be used with particular caution in the elderly and patients with renal
impairment.

Hypokalaemia predisposes to digoxin toxicity.

Digoxin levels may be increased by drugs such as amiodarone, calcium channel blockers,
quinine, hydroxychloroquine.
Older Patients - Digoxin
Loading and maintenance doses of digoxin should be adjusted according to renal function: age,
sex and weight need to be considered. A lower maintenance dose (i.e. 62.5-125 micrograms daily)
is usually adequate in older patients.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 2 of 31
Date: 11.7.2014
2.2 Diuretics
Thiazides and related diuretics

Bendroflumethazide/Bendrofluazide 2.5mg, 5mg tablet

Chlorothiazide 250mg/5ml and 100mg/5ml suspension (unlicensed)
Dose
- Bendroflumethiazide tablets 2.5mg, 5mg: hypertension, 2.5mg daily.
- Chlorothiazide suspension 250mg/5ml, 100mg/5ml: see BNF for Children
Prescribing notes

Allow 4 weeks for maximal antihypertensive effect of bendroflumethiazide.

Bendroflumethiazide may be prescribed with furosemide (frusemide) for severe heart failure
under hospital supervision; this must be carefully monitored.
Loop diuretics

Furosemide 20mg, 40mg, 500mg tablet

Furosemide 20mg/5ml, 40mg/5ml liquid

Furosemide 50mg/5ml injection

Bumetanide 1mg, 5mg tablet

Bumetanide 1mg/5ml liquid

Metolazone 5mg tablets (unlicensed)

Torasemide 5mg and 10mg tablets
Dose
- Furosemide tablets 20mg, 40mg, 500mg; liquid 20mg/5ml, 40mg/5ml: oedema, initially 40mg
daily then adjusted according to response.
- Furosemide injection 10mg/mL: slow intravenous injection, initially 20-50mg. Furosemide may be
given by intravenous infusion at a rate not exceeding 4mg/minute.
- Bumetanide tablets 1mg, 5mg; liquid 1mg/5ml: initially 1mg in the morning the adjusted
according to response
- Torasemide tablets 5mg, 10mg: initially 5mg in the morning the adjusted according to response.
Usual max is 40mg daily.
Prescribing notes

Furosemide produces a dose-dependent diuresis within 1 hour if given orally or 30 minutes if
given intravenously; duration of action, 6 hours.

Furosemide 500mg tablets are scored and can be halved.

Bumetanide may be an option in those patients that are not responding to furosemide (1mg
bumetanide is equivalent to 40mg furosemide).
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 3 of 31
Date: 11.7.2014
Potassium-sparing diuretics

Amiloride 5mg tablet

Amiloride 5mg/5ml solution
Dose
- Amiloride tablets 5mg; oral solution 5mg/5ml: 5-20mg daily.
Prescribing notes

Amiloride is a weak diuretic with potassium-sparing properties, given with other diuretics if
hypokalaemia is a problem; may take 2-3 days for full effect.

Use with caution in renal impairment.

Potassium-sparing diuretics such as amiloride are usually only necessary if hypokalaemia
develops
Aldosterone antagonists

Eplerenone 25mg, 50mg tablet

Spironolactone 25mg, 50mg, 100mg tablet

Spironolactone 50mg/5ml suspension (unlicensed)
Dose
- Eplerenone tablets 25mg, 50mg: initially 25mg once daily, increased within 4 weeks to 50mg
once daily.
- Spironolactone tablets 25mg, 50mg, 100mg: heart failure in conjunction with ACE inhibitor,
25mg daily; higher doses may be needed in liver failure.
Prescribing notes

Spironolactone is an aldosterone antagonist used for oedema in hepatic cirrhosis or heart
failure, and primary hyperaldosteronism.

Spironolactone 25mg daily has been shown to reduce mortality in patients with severe heart
failure receiving standard therapy including ACE inhibitors; renal function and electrolytes
should be monitored.

Use with caution in renal impairment.

Eplerenone is to be used as an adjunct in stable patients with left ventricular dysfunction with
evidence of heart failure following myocardial infarction (start therapy within 3-14 days of
event).

Eplerenone is an alternative aldosterone antagonist which may be prescribed for patients who
develop gynaecomastia with spironolactone.
Osmotic diuretics

Mannitol 10%, 20% infusion polyfusor
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 4 of 31
Date: 11.7.2014
Older Patients - Diuretics
All diuretics have the propensity to cause postural hypotension and thus collapse and falls in older
patients.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 5 of 31
Date: 11.7.2014
2.3 Anti-arrhythmic drugs
Supraventricular arrhythmias

Adenosine 3mg/ml injection

Adenosine 30mg/10ml (Restricted/unlicensed)
Supraventricular and ventricular arrhythmias

Amiodarone 100mg, 200mg tablet

Amiodarone 150mg/3ml injection

Amiodarone 300mg in 10ml prefilled syringe

Atenolol 25mg, 50mg, 100mg tablets

Atenolol 25mg/5ml syrup

Atenolol 5mg/10ml injection

Disopyramide 100mg capsule

Disopyramide 50mg/5ml injection

Flecainide 50mg, 100mg tablet

Flecainide 150mg/15ml injection

Propafenone 150mg tablet

Sotalol 40mg, 80mg, 160mg tablet

Verapamil tablets

Verapamil 5mg/2ml injection
Ventricular arrhythmias

Lidocaine/Lignocaine 0.2% in 500ml infusion

Lidocaine/Lignocaine 1% injection

Mexiletine 50mg capsules (unlicensed)
Dose
Anti-arrhythmics are complex agents; intravenous injections or infusions should be given
according to specialist advice.
- Disopyramide capsules 100mg: orally 300-800mg daily in divided doses
- Lidocaine injection 10mg/mL (1%), 20mg/mL (2%); infusion 1mg/mL (0.1%) and 2mg/mL
(0.2%) in glucose 5%, 500mL.
- Flecainide tablets 50mg, 100mg; injection 10mg/mL: orally, ventricular arrhythmias, 100mg
twice daily; max 400mg daily, reduced after 3-5 days if possible; supraventricular arrhythmias,
50mg twice daily; max 300mg daily.
- Atenolol tablets 25mg, 50mg, 100mg; syrup 25mg/5mL; injection 500micrograms/mL: orally, 50100mg daily.
- Amiodarone tablets 100mg, 200mg; injection 50mg/mL: orally, 200mg 3 times daily for 1 week,
then 200mg twice daily for 1 week, then usually 100-200mg daily thereafter.
- Sotalol (with ECG monitoring and measurement of corrected QT interval) tablets 40mg, 80mg,
160mg: orally, initially 80mg daily in 1-2 divided doses increased every 2-3 days to 160-320mg
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 6 of 31
Date: 11.7.2014
daily in 2 divided doses; 480-640mg daily for life-threatening ventricular arrhythmias.
- Verapamil tablets 40mg, 80mg, 120mg; m/r tablets 120mg, 240mg; m/r capsules 120mg,
180mg, 240mg; injection 2.5mg/mL: orally, supraventricular arrhythmias, 40-120mg 3 times daily
for standard preparation; m/r verapamil, dose according to brand. See BNF.
- Adenosine injection 3mg/mL.
- Atropine injection 100micrograms/mL, 200micrograms/mL, 300micrograms/mL,
600micrograms/mL.
- Digoxin tablets 62.5micrograms, 125micrograms and 250micrograms; elixir 50micrograms/mL;
injection 250micrograms/mL.
Prescribing notes

Amiodarone may cause corneal microdeposits, thyroid dysfunction, pneumonitis, peripheral
neuropathy and hepatotoxicity. Liver-function and thyroid-function tests should be performed
before treatment, and 6 monthly thereafter; chest X-ray should be done before treatment.

Patients receiving amiodarone should avoid exposure of the skin to direct sunlight or sun
lamps; a sunscreening product providing SPF 25 should be applied if amiodarone is
prescribed.

Amiodarone interacts with many drugs. There is a potential for drug interactions to occur for
several weeks (or even months) after treatment with it has been stopped.

Amiodarone and Sotalol may cause atypical VT (torsades de pointes); they should be given
with extreme caution with drugs known to prolong the QT interval e.g. erythromycin,
chloroquine, haloperidol, lithium, tricyclic antidepressants, chlorpromazine.

Sotalol should not be used for angina, hypertension, thyrotoxicosis or secondary prevention
after myocardial infarction. Sotalol should be avoided in patients on diuretics or with
hypokalaemia.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 7 of 31
Date: 11.7.2014
2.4 Beta-adrenoceptor blocking drugs

Atenolol 25mg, 50mg, 100mg tablets

Atenolol 25mg/5ml syrup

Atenolol 5mg/10ml injection

Bisoprolol 1.25mg, 2.5mg, 3.75mg, 5mg, 10mg tablet

Esmolol 100mg/10ml

Esmolol 2.5g/250ml (ITU only)

Labetolol 50mg, 100mg tablet

Labetolol 5mg/ml injection

Metoprolol 5mg/5ml injection

Metoprolol 25mg/5ml suspension (unlicensed)

Metoprolol 50mg, 100mg tablet

Nebivolol 5mg tablet

Propranolol 10mg, 40mg tablet

Propranolol 10mg/5ml solution

Propranolol M/R 80mg, 160mg capsule

Sotalol 40mg, 80mg, 160mg tablet
(For use in the treatment of heart failure only)
Dose
- Atenolol tablets 25mg, 50mg, 100mg; syrup 25mg/5mL: 25-100mg daily according to response.
- Bisoprolol tablets 1.25mg, 2.5mg, 3.75mg, 5mg, 7.5mg, 10mg: stable, chronic heart failure,
1.25mg daily for 1 week, increased, if well tolerated, to 2.5mg daily for 1 week, then 3.75mg daily
for 1 week, then 5mg daily for 4 weeks, then 7.5mg daily for 4 weeks, then 10mg daily
maintenance.
- Labetolol tablets 50mg, 100mg: see BNF
- Metoprolol tablets 50mg, 100mg, suspension 25mg/5ml: see BNF
- Propranolol tablets 10mg, 40mg, 80mg, 160mg: thyrotoxicosis (adjunct), anxiety tachycardia,
10-40mg 3-4 times daily. Anxiety with symptoms such as palpitations, sweating, tremor, 40mg once
daily increased to 40mg 3 times daily if necessary. Migraine prophylaxis, essential tremor: initially
40mg 2-3 times daily, maintenance 80-160mg daily.
Prescribing notes

Bisoprolol is second-line for patients intolerant of atenolol in hypertension.

Bisoprolol is first choice beta-blocker for stable, chronic heart failure initiated under specialist
supervision.

Beta-blockers may cause bronchospasm; avoid in patients suffering asthma. If a beta-blocker
is required, a cardioselective beta-blocker should be selected, initiated at a low dose and the
patient closely monitored.

Sotalol is only used as an anti-arrhythmic.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 8 of 31
Date: 11.7.2014

Propranolol is indicated for treatment of migraine, anxiety, thyrotoxicosis and essential
tremor.
2.5 Drugs affecting the renin-angiotensin system and other antihypertensive drugs
Vasodilator antihypertensive drugs

Hydralazine 25mg tablet

Hydralazine 20mg injection

Minoxidil 5mg tablet
Centrally acting antihypertensive drugs

Methyldopa 125mg, 250mg, 500mg tablet

Moxonidine 200 microgram, 300 microgram, 400 microgram tablet

Clonidine 100 microgram tablet

Clonidine 150 microgram/ml injection
Alpha-adrenoceptor blocking drugs
1st Choice

Doxazosin 1mg, 2mg, 4mg tablet
Alternatives

Prazosin 1mg tablet

Terazosin 2mg, 5mg tablet
Dose
- see BNF
Prescribing notes

Doxazosin is a third-line agent in the treatment of hypertension. It should be used with
caution in patients with heart failure or impaired left ventricular function.

Doxazosin may cause postural hypotension and first dose hypotension. Treatment should be
initiated at the lowest dose possible.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 9 of 31
Date: 11.7.2014
Angiotensin-converting enzyme inhibitors

Captopril 12.5mg, 25mg tablet

Enalapril 2.5mg, 5mg, 10mg tablet

Lisinopril 2.5mg, 5mg, 10mg, 20mg tablet

Perindopril 2mg, 4mg tablet

Ramipril 1.25mg, 2.5mg, 5mg, 10mg capsule

Ramipril 2.5mg/5ml oral solution
Dose
- see BNF
Prescribing notes

For heart failure the dose of the ACE inhibitor should be titrated to a 'target' dose (or to the
maximum tolerated dose if lower). See BNF.

Urea and electrolytes should be checked within 2 week of commencing therapy and after any
dose change.

Ramipril should be prescribed as a once daily dose. Patients who have been initiated on twice
daily dosing should be switched to an equivalent once daily dose.

Ramipril 2.5mg/5ml oral solution is approved for use in patients with short-term swallowing difficulties or
enteral feeding tubes only. If required long-term then clinical need for patient to remain on therapy should
be reconsidered.
Angiotensin-II receptor antagonists

Candesartan 2mg, 4mg, 8mg, 16mg and 32mg tablets

Irbesartan 75mg, 150mg tablet

Losartan 25mg, 50mg tablet

Valsartan 40mg, 80mg and 160mg capsules
Dose
- Candesartan tablets 2mg, 4mg, 8mg, 16mg, 32mg: recommended dose is 4-32 daily. See BNF.
- Irbesartan tablets 75mg, 150mg, 300mg: recommended dose is 150-300mg once daily (in
haemodialysis or in elderly over 75 years, initial dose of 75mg once daily may be used). See BNF.
- Valsartan capsules 80mg, 160mg: 40mg-160mg daily. See BNF
Prescribing notes

Angiotensin-II receptor antagonists should be reserved for patients who develop a persistent
cough with ACE inhibitors.

Urea and electrolytes should be checked within 2 weeks of commencing therapy and after
any change in dose.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 10 of 31
Date: 11.7.2014
MHRA Drug Safety Update
Combination use of medicines from different classes of renin-angiotensin system blocking
agents: risk of hyperkalaemia, hypotension, and impaired renal function—new warnings
Article date: June 2014
Summary
Combination use of medicines from different classes of renin-angiotensin system blocking agents is
associated with an increased risk of hyperkalaemia, hypotension, and impaired renal function. New
warnings have been agreed following an EU-wide review. In particular, prescribers are advised that
people with diabetic nephropathy should not be given an ACE-inhibitor with an angiotensin-receptor
blocker as they are already prone to developing hyperkalaemia. Combining aliskiren with an ACEinhibitor or angiotensin-receptor blocker is contraindicated in people with kidney impairment or
diabetes.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON426905
Miscellaneous

Phenoxybenzamine 10mg capsules

Phentolamine 10mg/ml injection

Guanethidine 10mg/ml injection (Theatres only) (Unlicensed)

Iloprost nebules 10microgram/ml (Critical Care Only)
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 11 of 31
Date: 11.7.2014
2.6 Nitrates, calcium-channel blockers, and other anti-anginal drugs
Nitrates

Glyceryl trinitrate 400 microgram/dose spray

Glyceryl trinitrate 300microgram, 500microgram sublingual tablets

Glyceryl trinitrate 5mg, 10mg skin patch

Glyceryl trinitrate 5mg/5ml injection

Isosorbide mononitrate 10mg, 20mg tablet

Isosorbide dinitrate 10mg, 20mg tablet

Isosorbide dinitrate 25mg/50ml injection
Dose
- Glyceryl trinitrate spray 400micrograms per puff; sublingual tablets 300micrograms,
500micrograms: sublingually, 300microgram-1mg repeated as required.
- Isosorbide mononitrate tablets 10mg, 20mg:: 20 - 40mg twice daily (10mg twice daily in those
who have not previously received nitrates); up to 120mg daily in divided doses if required.
- Isosorbide dinitrate tablets 10mg, 20mg: see BNF
Prescribing notes

To reduce the risk of nitrate tolerance, isosorbide mononitrate should be given twice daily 6-8
hours apart.

Long-acting and transdermal nitrate preparations are significantly more expensive than
standard formulations. A cost-effective branded long-acting preparation should be prescribed
only for patients who have a problem with compliance.

Glyceryl trinitrate (GTN) intravenous injection may be given when sublingual or buccal GTN is
ineffective in patients with chest pain due to myocardial infarction or severe ischaemia, and
in treatment of acute left ventricular failure.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 12 of 31
Date: 11.7.2014
Calcium-channel blockers

Amlodipine 5mg, 10mg tablet

Diltiazem 60mg M/R tablets (Tildiem®

Diltiazem 120mg, 240mg, 180mg, 300mg and 360mg s/r capsule (Viazem XL®)

Diltiazem 200mg M/R capsules (Tildiem LA®)

Lercanidipine 10mg tablets

Nifedipine 5mg, 10mg capsule - Instant release formulation

Nifedipine 10mg, 20mg s/r tablet (Adalat retard®) - 12 hourly formulation

Nifedipine 10mg, 20mg m/r capsules (Coracten SR®) - 12 hourly formulation

Nifedipine 30mg and 60mg XL capsules (Coracten XL®) - 24 hourly formulation

Nimodipine 30mg tablet, 10mg/50ml injection

Verapamil 40mg, 80mg,120mg tablet

Verapamil 120mg s/r capsule

Verapamil 40mg/5ml SF solution

Verapamil 2.5mg/ml injection
Dose
- Amlodipine tablets 5mg, 10mg: hypertension or angina, initially 5mg once daily; max. 10mg
once daily.
- Diltiazem m/r tablets 60mg, 90mg, 120mg; m/r capsules 60mg, 90mg, 120mg, 180mg, 200mg,
240mg, 300mg, 360mg: dose according to brand. See BNF.
- Verapamil tablets 40mg, 80mg, 120mg; m/r capsules 120mg: dose according to brand. See BNF.
Prescribing notes

Sudden withdrawal of calcium-channel blockers may exacerbate angina; withdraw if
ischaemic pain occurs or worsens after starting treatment.

Short-acting formulations of nifedipine capsules have been associated with large variations in
blood pressure and reflex tachycardia; they are no longer recommended for angina or
hypertension.

Diltiazem is first choice calcium-channel blocker for angina if a beta-blocker cannot be used;
it is also given for hypertension. It has less negative inotropic effects than verapamil and
significant myocardial depression is rare. Use caution if given with beta-blockers due to risk
of bradycardia. The most cost-effective brand should be prescribed.

Verapamil is used for angina, hypertension and arrhythmia; it reduces cardiac output, slows
the heart rate and may affect atrioventricular conduction. It should not be used with betablockers.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 13 of 31
Date: 11.7.2014
Other Anti-anginal drugs

Nicorandil 10mg, 20mg tablet

Ivabradine 5mg, 7.5mg tablets

Ranolazine 375mg, 500mg tablets
Dose
- see BNF
Prescribing notes

Nicorandil is used when other anti-anginal drugs are insufficient; they have similar efficacy to
other anti-anginal drugs in controlling symptoms but there is little evidence regarding their
efficacy in combination with other anti-anginal drugs.

Ivabradine is approved for use, on the initiation of a cardiologist, chronic stable angina in
patients for whom heart rate control is desirable and also have a contra-indication or
intolerance of beta-blockers and rate limiting calcium channel blockers.

Ivabradine is also approved for use, on the initiation of a specialist, for chronic heart failure
NHYA class II to IV with systolic dysfunction, in patients in sinus rhythm and whose heart
rate is ≥75 beats per minute (bpm), in combination with standard therapy including betablockers therapy or when beta-blockers therapy is contraindicated or not tolerated.

In patients prescribed ivabradine the resting ventricular rate should not drop below 50bpm.

Ranolazine is indicated as adjunctive therapy in the treatment of stable angina in patients
inadequately controlled or intolerant of first-line antianginal therapies.
MHRA Drug Safety Update
Nicorandil: Gastrointestinal ulceration
Article date: June 2008
Summary
Nicorandil is associated with a risk of gastrointestinal ulceration, including perianal ulceration.
Healthcare professionals should consider nicorandil treatment as a possible cause in patients who
present with symptoms of gastrointestinal-tract ulceration
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON085019
MHRA Drug Safety Update
Ivabradine: emerging clinical trial evidence of increased cardiovascular risk—carefully
monitor for bradycardia
Article date: June 2014
Summary
Ivabradine (Procorolan) is used to treat symptoms of long-term stable angina in adults with
coronary heart disease who have a normal heart rhythm. Ivabradine is also used in patients with
long-term heart failure who have a normal heart rhythm but whose heart rate is at least 75 beats
per minute (bpm).
The SIGNIFY trial investigated the efficacy of ivabradine compared with placebo in people with
coronary artery disease. The ivabradine dose regimen used in the trial (7.5 to 10 mg twice daily)
was higher than the licensed posology (5 to 7.5 mg twice daily). The trial included a pre-specified
subgroup analysis of participants with symptomatic angina of CCS class II or more. Preliminary
results have shown a small but statistically significant increase in the combined risk of
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 14 of 31
Date: 11.7.2014
cardiovascular death and non-fatal myocardial infarction with ivabradine compared with placebo in
this subgroup. This cardiovascular risk might be associated with a target heart rate below 60 bpm.
The European Medicines Agency is reviewing how the data from the SIGNIFY study impact the
balance of benefits and risks of ivabradine. While the review is ongoing, we remind you of the
following:
Advice for healthcare professionals:
- The starting dose of ivabradine is 5 mg twice daily. The maintenance dose should not exceed 7.5
mg twice daily.
-Carefully monitor patients for bradycardia or its symptoms (eg, dizziness, fatigue, hypotension).
-Down-titrate the dose if resting heart rate decreases persistently below 50 bpm or if the patient
experiences symptoms of bradycardia. The dose can be down-titrated to 2.5 mg twice daily if
necessary.
-Stop ivabradine treatment if the resting heart rate remains below 50 bpm or symptoms of
bradycardia persist.
-Only increase the dose to 7.5 mg twice daily after 3 to 4 weeks of treatment and if the 5 mg dose is
well tolerated but insufficient. Carefully monitor the effect of a dose increase on heart rate.
-Avoid concomitant use of ivabradine with heart rate-reducing calcium channel blockers such as
verapamil or diltiazem.
-Review the treatment of patients currently using ivabradine where appropriate.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON428305
Peripheral vasodilators and related drugs

Pentoxyfilline 400mg tablets

Naftidrofuryl 100mg capsules
Prescribing notes

Patients suffering intermittent claudication should be advised to exercise and stop smoking.
First-line management of Raynaud's phenomenon includes avoiding exposure to cold and
stopping smoking.

Peripheral vasodilators are of limited value.

Naftidrofuryl, cilostazol, pentoxifylline and inositol are not recommended for the treatment of
intermittent claudication.
2.7 Sympathomimetics
Inotropic sympathomimetics

Dobutamine 250mg/20ml injection

Dopamine 200mg/5ml injection

Dopexamine 50mg/5ml injection

Isoprenaline 2.25mg/2ml injection (unlicensed)
Vasoconstrictor sympathomimetics

Ephedrine 30mg/ml injection
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 15 of 31
Date: 11.7.2014

Metaraminol 10mg/ml injection (unlicensed)

Noradrenaline/Norepinephrine 2mg/ml injection

Phenylephrine 10mg/ml injection (ITU only)
Cardiopulmonary resuscitation

Adrenaline/Epinephrine 100 micrograms/ml(1:10,000) minijet

Adrenaline/Epinephrine 100 micrograms/ml(1:10,000) injection
Dose
- See BNF for dosing recommendations.
- Adrenaline injection 100micrograms/mL: during cardiopulmonary resuscitation (CPR), 1mg
(10mL) intravenously flushed with saline, and repeated every 3 minutes.
- Dobutamine strong sterile solution,12.5mg/mL and 50mg/mL.
- Dopamine sterile concentrate, 40mg/mL and 160mg/mL; intravenous infusion, 400mg or 800mg
in 250mL glucose 5%.
- Noradrenaline acid tartrate injection 2mg/mL (equivalent to noradrenaline base 1mg/mL).
Prescribing notes

Inotropic and vasoconstrictor sympathomimetics should preferably be used only in the
intensive care setting with invasive haemodynamic monitoring.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 16 of 31
Date: 11.7.2014
2.8 Anticoagulants and protamine
Parenteral anticoagulants

Fondaparinux 2.5mg syringe (Haematology advice only)

Danaparoid sodium 750units Injection (Haematology advice only)
Standard heparins

Heparin 20000units/20ml, 5000units/5ml injection

Heparin 5000 units/0.2ml (Calciparine®)

Heparin 50 units/5ml (Hepsal®)
Low molecular weight heparins

Enoxaparin 20mg, 40mg, 60mg, 80mg, 100mg and 150 mg pre-filled syringe

Tinzaparin 20000 units/ml (2ml) vial

Tinzaparin 20000 unit/ml pre-filled syringes (10000, 14000, 18000, 40000 units)

Tinzaparin 10000/ml pre-filled syringes (2500, 3500, 4500 units)
Dose
- See BNF for dosing recommendations.
- Standard heparin 1000units/mL, 20 000units/20mL.
- Enoxaparin 100mg/mL (0.2mL, 0.4mL, 0.6mL, 0.8mL and 1mL syringes); 150mg/mL (0.8mL,
1mL syringes).
- Tinzaparin 10,000 units/mL (0.25mL, 0.35mL, 0.45mL syringes or 2mL vial) or 20,000 units/mL
(0.5mL, 0.7mL, 0.9mL syringes or 2mL vial).
Prescribing notes

See Trust “Unfractionated Heparin Dosing Guidelines”.

See Trust Thrombophylaxis guidelines on use of LMWHs.

Treatment with standard heparin is continued until no longer required, or until warfarin takes
effect (at least 3 days).

Heparin is monitored using activated partial thromboplastin time (APTT) to give a
patient/control ratio of 2.0-3.0.

Low molecular weight heparin does not require APTT monitoring; if necessary, anti-factor Xa
can be monitored.

Heparins may induce two types of thrombocytopenia: the first, usually develops within 1-4
days of initiation, is acute, usually mild, and may resolve spontaneously. The second type has
an immunological basis and is more serious: it usually occurs after 7-11 days, or more
quickly in previously exposed patients, and is often associated with serious thromboembolic
complications or bleeding. Serial platelet counts should be measured if heparin is given for
longer than 5 days (or sooner if previously exposed), and heparin stopped if
thrombocytopenia develops.

Protamine sulphate reverses the effects of standard heparin, but only partially reverses the
effects of low molecular weight heparins.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 17 of 31
Date: 11.7.2014
Epoprostenol

Epoprostenol 500 microgram vial
Oral anticoagulants

Warfarin 1mg, 3mg and 5mg tablets

Phenindione 10mg, 25mg and 50mg tablets

Dabigatran 75mg capsules – approved for use as per NICE TA157 as a treatment option for the prevention
of VTE after elective hip or knee replacement.

Dabigatran 110mg capsules - approved for use as per NICE TA157 as a treatment option for the
prevention of VTE after elective hip or knee replacement

Dabigatran 110mg and 150mg capsules - for use as per NICE TA249 as a treatment option for the
prevention of stoke & systemic embolism in patients with AF.

Rivaroxaban 10mg tablets - approved for use as per NICE TA157 as a treatment option for the prevention
of VTE after elective hip or knee replacement. The preferred treatment options locally are warfarin or
dabigatran, but rivaroxaban is in option in those patients who require their medication in a compliance aid.

Rivaroxaban 15mg, and 20mg tablets - as per NICE TA249 as a treatment option for the prevention of
stoke & systemic embolism in patients with AF. The preferred treatment options locally are warfarin or
dabigatran, but rivaroxaban is in option in those patients who require their medication in a compliance aid.
Also approved for patients with DVT/PE whom the anticoagulant service have identified as difficult to
manage on warfarin and/or tinzaparin, and have referred to a haematologist for advice on their
management. Rivaroxaban remains non-formulary for all newly diagnosed DVT/PE patients as this
requires input from the CCG commissioners to redesign the DVTPE pathway in Gateshead and the service
provided by the ambulatory clinic on MAU. All newly diagnosed patients should continue to receive warfarin
and tinzaparin as per current practice

Apixaban 2.5mg tablets - not a preferred option in the current pathways locally but is available on individual
patient basis as per NICE Technology Appraisal TA245 for the prevention of VTE after elective hip or knee
replacement, OR as per NICE Technology Apprasisal TA275 for preventing stroke and systemic embolism
in people with nonvalvular atrial fibrillation.

Apixaban 2.5mg tablets and 5mg tablets - not a preferred option in the current pathways locally but is
available on individual patient basis as per NICE Technology Appraisal TA275 for preventing stroke and
systemic embolism in people with nonvalvular atrial fibrillation.
Dose
- Warfarin tablets 500micrograms (white), 1mg (brown), 3mg (blue), 5mg (pink): induction dose
10mg daily for 2 days, then adjusted according to INR. A lower induction dose may be required by
some patients; see BNF for details.
Prescribing notes

See Trust “GUIDELINES FOR WARFARIN- INDUCTION and MAINTENANCE DOSES”

The warfarin dose is adjusted according to the international normalised ratio (INR). The
target INR should be clearly identified at initiation of therapy, and measured daily or on
alternate days initially, then at longer intervals (depending on response) then up to every 12
weeks.

Indication and duration of treatment should be clearly recorded at initiation of treatment; the
patient-held anticoagulant treatment booklet should be used. See BNF for details.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 18 of 31
Date: 11.7.2014

The plasma half-life of warfarin is 35 hours; a steady anticoagulant effect is achieved after
about one week. If immediate anticoagulation is required, heparin must be given
concomitantly.

There are many clinically important interactions with warfarin; clinicians are strongly advised
to consult BNF before prescribing.

Vitamin K (phytomenadione) can be given to reverse the effects of warfarin but takes 6-12
hours to become effective. Immediate reversal of the anticoagulant effect of warfarin may be
achieved with fresh frozen plasma or prothrombin complex concentrate; see BNF for details.
Specialist haematological advice should be sought.

Dabigatran is approved for use in hip and knee replacement surgery for prophylaxis of
venous thromboembolism.

Warfarin will continue to be the first line drug of choice for prevention of stroke in patients
with non-valvular AF but Dabigitran/Rivaroxaban/Apixaban be considered for patients with a
warfarin allergy or an absolute contra-indication to warfarin
(Dabigitran/Rivaroxaban/Apixaban may also be contra-indicated in some of these
indications). Please note that a bleeding risk that would lead to a contra-indication to
warfarin would also contra-indicate to Dabigitran/Rivaroxaban/Apixaban.
Older Patients - Warfarin
Warfarin should be used with caution in patients with confusion or a tendency to fall.
MHRA Drug Safety Update
Dabigatran (Pradaxa▼): risk of serious haemorrhage – contraindications clarified and
reminder to monitor renal function
Article date: July 2012
Summary
Because of the risk of haemorrhage, dabigatran is contraindicated in a range of clinical conditions where the
patient is at significant risk of major bleeding (listed in the main article). Dabigatran is also now contraindicated with
dronedarone, and with the use of other anticoagulant agents, except when switching therapy to or from dabigatran,
or with the use of unfractionated heparin for maintenance of venous or arterial catheter patency.
In addition, as exposure to dabigatran is substantially increased in patients with renal insufficiency, renal function
should be assessed in all patients before starting dabigatran and at least once a year in patients older than 75
years or those with a suspected decline in renal function.Nicorandil is associated with a risk of
gastrointestinal ulceration, including perianal ulceration. Healthcare professionals should consider
nicorandil treatment as a possible cause in patients who present with symptoms of gastrointestinaltract ulceration
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON175429
MHRA Drug Safety Update
Dabigatran (Pradaxa▼): contraindicated in patients with prosthetic heart valve(s)
requiring anti-coagulant treatment, because of the risk of thrombosis and haemorrhage
Article date: March 2013
Summary
Dabigatran (Pradaxa) is now contraindicated in patients with prosthetic heart valves requiring anti-coagulant
treatment related to their valve surgery. This is regardless of the length of time elapsed since valve replacement
took place.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 19 of 31
Date: 11.7.2014
The contraindication is based on new clinical trial data in this population, which showed an increased frequency of
thromboembolic and bleeding events in the group of patients treated with dabigatran, compared with warfarin.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON252010
MHRA Drug Safety Update
New oral anticoagulants apixaban (Eliquis▼), dabigatran (Pradaxa) and rivaroxaban
(Xarelto▼): risk of serious haemorrhage—clarified contraindications apply to all three
medicines
Article date: October 2013
Summary
Updated advice on contraindications and warnings:
The following contraindications now apply to all three new oral anticoagulants, for all doses and indications:


A lesion or condition, if considered a significant risk factor for major bleeding. This may include:
o
current or recent gastrointestinal ulceration
o
presence of malignant neoplasm at high risk of bleeding
o
recent brain or spinal injury
o
recent brain, spinal, or ophthalmic surgery
o
recent intracranial haemorrhage
o
known or suspected oesophageal varices
o
arteriovenous malformation
o
vascular aneurysms, or major intraspinal or intracerebral vascular abnormalities
Concomitant treatment with any other anticoagulant agent—eg, unfractionated heparin, low molecular
weight heparin (such as enoxaparin or dalteparin), heparin derivatives (such as fondaparinux), or oral
anticoagulants (such as warfarin). Exceptions are switching of therapy to or from the medicine, or when
unfractionated heparin is given at doses necessary to maintain an open central venous or arterial catheter
Additional advice and information for healthcare professionals:

Special care should be taken when deciding to prescribe these anticoagulant medicines to patients with
other conditions, procedures, and concomitant treatments (eg, non-steroidal anti-inflammatory drugs,
antiplatelets), which may increase the risk of major bleeding

Attention should be paid to renal function. Impaired renal function may constitute a contraindication or
recommendation not to use the anticoagulant medicine, or may require a dose reduction;
recommendations differ for the three medicines

The contraindications, posology, and warnings and precautions for use specific to each medicine, together
with the individual’s risk factors for bleeding (eg, renal function), should be considered before prescribing
these medicines
There is no specific antidote available for any of these three new oral anticoagulants. Please consult the
product information for advice on treatment in the event of bleeding complications, or overdose.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON322740
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 20 of 31
Date: 11.7.2014
Protamine

Protamine 50mg/5ml injection
Prescribing notes

Protamine sulphate reverses the effects of standard heparin, but only partially reverses the
effects of low molecular weight heparins.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 21 of 31
Date: 11.7.2014
2.9 Antiplatelet drugs

Aspirin 75mg and 300mg dispersible tablets

Aspirin 75mg and 300mg e/c tablets

Aspirin 150mg suppositories

Clopidogrel 75mg tablets

Dipyridamole 50mg/5ml suspension

Dipyridamole 200mg s/r capsules

Prasuguel 5mg and 10mg tablets

Ticagrelor 90mg tablets

Tirofiban 12.5mg/50ml injection
Dose
- Aspirin dispersible tablets 75mg, 300mg: prophylaxis of cerebrovascular disease or myocardial
infarction, initial loading dose of 150-300mg, then 75mg daily.
- Clopidogrel tablets 75mg: for acute coronary syndrome, 75mg once daily for up to 12 months in
combination with aspirin. An initial loading dose of clopidogrel 300mg is recommended.
- Dipyridamole SR capsules 200mg: for secondary prevention of ischaemic stroke and transient
ischaemic attacks (used alone or combination with aspirin) 200mg capsule twice daily.
- Prasugrel tablets 5mg, 10mg: (with aspirin) initially 60mg as a single dose then body-weight over
60kg, 10mg once daily or body-weight under 60kg or over 75 years, 5mg once daily.
- Tirofiban injection 12.5mg/50ml: see BNF
- Ticagrelor tablets 90mg: see BNF
Prescribing notes

The e/c formulations of aspirin are not recommended.

Dipyridamole m/r or low dose aspirin may be used with warfarin for prophylaxis of
thromboembolism due to prosthetic heart valves.

Patients with proven intolerance to aspirin may be prescribed clopidogrel to prevent further
events in stroke, myocardial infarction or peripheral vascular disease.

Aspirin and clopidogrel may be prescribed concomitantly for acute coronary syndrome for up
to 12 months, after which clopidogrel is discontinued.

Hospital specialists may prescribe clopidogrel for up to 3 months to prevent coronary artery
stent occlusion.

The combination of dipyridamole and clopidogrel has not been adequately evaluated and is
therefore not recommended.

There is a clinically significant interaction between clopidogrel and omeprazole making
clopidogrel less effective. If concomitant use of clopidogrel and a proton pump is necessary,
then lansoprazole would be an appropriate choice.

Prasugel in combination with aspirin 75mg is an option for treatment acute coronary
syndrome undergoing PCI.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 22 of 31
Date: 11.7.2014
MHRA Drug Safety Update
Clopidogrel: risk of acquired haemophilia
Article date: December 2013
Summary
Reports of acquired haemophilia have been received in association with clopidogrel. This very rare but serious
condition may be missed due to the established risk of bleeding associated with clopidogrel treatment.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON350671
MHRA Drug Safety Update
Prasugrel (Efient▼): rare but serious hypersensitivity reactions
Article date: May 2011
Summary
Prasugrel (Efient▼) has been rarely associated with reports of serious hypersensitivity reactions including, very
rarely, angioedema; some of which occurred in patients with a history of hypersensitivity to clopidogrel. Healthcare
professionals should be aware of this risk when prescribing prasugrel.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON117322
MHRA Drug Safety Update
Clopidogrel and proton pump inhibitors: interaction—updated advice
Article date: April 2010
Summary
In light of the most recent evidence, the previous advice on the concomitant use of clopidogrel with proton pump
inhibitors has now been modified. Use of either omeprazole or esomeprazole with clopidogrel should be
discouraged. The current evidence does not support extending this advice to other PPIs.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON087711
MHRA Drug Safety Update
Prasugrel: increased risk of bleeding – information on timing of loading dose
Article date: January 2014
Summary
New clinical trial information is available on the timing of the loading dose of prasugrel when used in
patients with unstable angina or non-ST segment elevation myocardial infarction.
In these patients, when coronary angiography is done within 48 hours after admission, the loading
dose should only be given at the time of percutaneous coronary intervention. This is to minimise the
risk of bleeding.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON364156
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 23 of 31
Date: 11.7.2014
2.10 Myocardial infarction and fibrinolysis

Alteplase 20mg and 50mg injection

Streptokinase 1.5million and 250000 unit injection

Tenecteplase 50mg injection
(a) acute myocardial infarction
First choice: tenecteplase
Prescribing notes

Thrombolysis is effective if given as soon as possible after acute myocardial infarction; urgent
transfer to hospital is essential.

Tenecteplase has the advantage of availability as a single, weight adjusted, intravenous bolus
injection. It can also be used in patients who have ever received streptokinase, suffered a
recent streptococcal infection or developed a hypersensitivity reaction to streptokinase.

If severe bleeding occurs, the fibrinolytic should be discontinued; coagulation factors and/or
tranexamic acid may be required.
(b) acute ischaemic stroke
First choice: alteplase
Prescribing notes

Alteplase must be used in strict accordance with detailed protocols in a specialist acute stroke
unit.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 24 of 31
Date: 11.7.2014
2.11 Antifibrinolytic drugs and haemostatics

Etamsylate 500mg tablets

Tranexamic acid 100mg/ml injection

Tranexamic acid 500mg tablets

Factor VIIa 1mg and 5mg injection (Novoseven®)

Prothrombin complex 250unit, 500unit and 1000unit injection (Beriplex®)
Dose
- Tranexamic acid tablets 500mg; injection 100mg/mL: orally, menorrhagia (initiated when heavy
bleeding has started), 1-1.5g 3-4 times daily for 3-4 days. Slow intravenous injection: local
fibrinolysis 0.5-1g 3 times daily.
- Other products: see BNF or product literature
Prescribing notes

The manufacturer recommends regular eye examinations and liver function tests when
tranexamic acid is used long-term for hereditary angioneurotic oedema; however, the BNF
states that the need for regular eye examinations during long-term treatment is based on
unsatisfactory evidence.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 25 of 31
Date: 11.7.2014
2.12 Lipid-regulating drugs
Anion-exchange resins

Colestyramine 4g sachets
Fibrates

Bezafibrate 200mg tablets

Bezafibrate 400mg m/r tablets

Ciprofibrate 100mg tablets

Fenofibrate MR 160mg tablets
Prescribing notes

Fibrates have been less well tested in clinical trials. They are mainly of benefit in those with
mixed hyperlipidaemia and low HDL cholesterol.
Statins

Atorvastatin 10mg, 20mg, 40mg and 80mg tablets

Atorvastatin 10mg and 20mg chewable tablets

Pravastatin 10mg, 20mg and 40mg tablets

Simvastatin 10mg, 20mg and 40mg tablets

Simvastatin 40mg/5ml oral solution

Rosuvastatin 5mg, 10mg and 20mg tablets
Dose
- Atorvastatin tablets 10mg, 20mg, 40mg, 80mg: hyperlipidaemia, 10-80mg at night
- Simvastatin tablets 10mg, 20mg, 40mg, 80mg: hyperlipidaemia, 10-80mg at night; coronary
heart disease, initially 20mg at night, max 80mg at night.
- Pravastatin tablets 10m, 20mg, 40mg: see BNF
- Rosuvastatin tablets 5mg, 10mg, 20mg: see BNF
Prescribing notes

Lowering cholesterol is associated with reduced mortality and morbidity in patients at high
and moderate risk of, or with established, cardiovascular and cerebrovascular disease.

Pravastatin is less likely to interact with other drugs than atorvastatin or simvastatin and
may be preferred in certain situations, such as in patients receiving warfarin, digoxin or
ciclosporin.

Generic simvastatin is substantially lower cost than other lipid lowering agents.

Caution should be exercised when prescribing other drugs with statins. Simvastatin and
atorvastatin interact with many drugs including azole antifungals, macrolide antibiotics,
amiodarone, verapamil, grapefruit juice and warfarin. See BNF for full list of interactions.

Caution should be exercised when prescribing simvastatin 80mg daily due to the increased
risk of adverse effects.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 26 of 31
Date: 11.7.2014

Simvastatin 40mg/5ml oral solution - approved for use in patients with short-term swallowing difficulties or
enteral feeding tubes only. If required long-term then clinical need for patient to remain on on a statin
should be reconsidered.

Atorvastatin 10mg and 20mg chewable tablets – approved for use in patients with swallowing difficulties
who require a statin.
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 27 of 31
Date: 11.7.2014
MHRA Drug Safety Update
Simvastatin: evidence supporting recent advice on dose limitations with concomitant
amlodipine or diltiazem
Article date: October 2012
Summary
In August 2012 we published advice that simvastatin is now contraindicated with concomitant use of certain
medicines, such as ciclosporin, danazol, and gemfibrozil. In addition, the recommendations for the maximum
dose of simvastatin have changed when used with a number of other medicines, including amlodipine and
diltiazem. These changes were driven primarily by concerns about an increased risk of myopathy and/or
rhabdomyolysis at higher plasma concentrations of simvastatin, which may result from such drug interactions.
Following further consideration by the Pharmacovigilance Expert Advisory Group of the Commission on Human
Medicines, this article summarises the evidence underlying the new advice that the maximum recommended
dose for simvastatin in conjunction with amlodipine and diltiazem is now 20 mg/day. The prescribed doses of
amlodipine and diltiazem need not be changed.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON199561
MHRA Drug Safety Update
Simvastatin: evidence supporting recent advice on dose limitations with concomitant
amlodipine or diltiazem
Article date: August 2012
Summary
We have previously communicated on the increased risk of myopathy associated with use of high-dose simvastatin (80 mg
daily) – see Drug Safety Update May 2010.
Considering the risk of myopathy associated with simvastatin, recent analysis of clinical trial data, spontaneously reported
cases and drug- drug interaction studies has resulted in further changes to the simvastatin prescribing information.
The changes include contraindications to concomitant use with certain medicines and maximum dose recommendations
when simvastatin is taken with a number of other medicines, as these interactions may increase plasma concentrations of
simvastatin which is associated with an increased risk of myopathy and/or rhabdomyolysis. Key points to note are that:


Simvastatin is now contraindicated with ciclosporin, danazol and gemfibrozil
The maximum recommended dose for simvastatin in conjunction with amlodipine or diltiazem is now 20 mg/day

A full updated listing of all the interactions is provided in the table below:
Drug interactions associated with increased risk of myopathy/rhabdomyolysis
Interacting agents
Itraconazole
Ketoconazole
Posaconazole
Erythromycin
Clarithromycin
Telithromycin
HIV protease inhibitors (eg, nelfinavir)
Nefazodone
Ciclosporin
Danazol
Gemfibrozil
Prescribing recommendations
Contraindicated with simvastatin
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 28 of 31
Date: 11.7.2014
Other fibrates (except fenofibrate)
Amiodarone
Amlodipine
Verapamil
Diltiazem
Do not exceed 10 mg simvastatin daily
Do not exceed 20 mg simvastatin daily
Patients should be closely monitored. Temporary
suspension of simvastatin treatment may be
considered.
Avoid grapefruit juice when taking simvastatin
Fusidic acid
Grapefruit juice
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON180637
MHRA Drug Safety Update
Statins: risk of hyperglycaemia and diabetes
Article date: January 2012
Summary
Statin use may be associated with a level of hyperglycaemia in some patients where formal diabetes care is
appropriate. The risk appears to be mainly in patients already at increased risk of developing diabetes.
However, the overall benefits of statins strongly outweigh any risks, including in those at risk of developing
diabetes or those with pre-existing diabetes.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON140667
MHRA Drug Safety Update
Simvastatin: increased risk of myopathy at high dose (80 mg)
Article date: May 2010
Summary
There is an increased risk of myopathy associated with high-dose (80 mg) simvastatin. The 80-mg dose should
be considered only in patients with severe hypercholesterolaemia and high risk of cardiovascular complications
who have not achieved their treatment goals on lower doses, when the benefits are expected to outweigh the
potential risks.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON085169
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 29 of 31
Date: 11.7.2014
Other

Ezetimibe 10mg tablets
Dose
- Ezetimibe tablets 10mg: 10mg once daily.
MHRA Drug Safety Update
Tredaptive (combined niacin-laropiprant): no longer for prescribing as preliminary
HPS2-THRIVE trial failed to show benefit outweighs risks
Article date: January 2013
Summary
Tredaptive has been withdrawn from the UK market since 18th January 2013.
Patients currently taking Tredaptive should make a non-urgent appointment to dicuss their treatment options
with their doctor.
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON228751
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 30 of 31
Date: 11.7.2014
2.13 Local sclerosants

Ethanolamine oleate 5% injection

Sodium tetradecyl sulphate 0.5%, 1% and 3% injection
Red = Hospital use only
Green = GP & Hospital use. Drugs not classified as Red, Amber or Green+ are classified as Green by default
Amber = Drugs with shared care agreement
Green+ = Initiated by Hospital specialist only
Gateshead Health NHS Foundation Trust
Drug Formulary
Page 31 of 31
Date: 11.7.2014