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 Formulary Chapter 2: Cardiovascular system - Full Chapter
Notes:

Chapter complete - updated July 18

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02.01  Positive inotropic drugs
02.01.01  Cardiac glycosides
 note 

Digoxin is most useful for controlling ventricular response in persistent and permanent arial fibrillation and atrial flutter. Digoxin also has a role in heart failure.
Digoxin has a long half life and maintenance doses need to be given only once daily (although higher doses may be divided to avoid nausea); renal function is the most important determinant of digoxin dosage.
Unwanted effects depend on both the concentration of digoxin in the plasma and on the sensitivity of the conducting system or of the myocardium, which is often increased in heart disease. It can sometimes be difficult to distinguish between toxic effects and clinical deterioration because symptoms of both are similar. The plasma concentration alone cannot indicate toxicity reliably, but the likelihood of toxicity increases progressively through the range 1.5 to 3micrograms/litre for digoxin. Digoxin should be used with special care in the elderly, who may be particularly susceptible to digitalis toxicity.
Regular monitoring of plasma-digoxin concentration during maintenance treatment is not necessary unless problems are suspected. Hypokalaemia predisposes the patient to digitalis toxicity; it is managed by giving a potassium-sparing diuretic, or if necessary, potassium supplementation.

Digoxin
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Formulary
  • Available as:
    • Tablet £
    • Elixir ££/60mL
    • Injection £/5 vials
  • Bioavailabilities are approximately: injection 100%, elixir 75%, tablet 63%
  • ONE 62.5mcg tablet is ~ equivalent to 50mcg (1mL) elixir
 
   
02.01.01  Digoxin-specific antibody
 note 

Serious cases of digoxin toxicity should be discussed with the National Poisons Information Service. Digoxin-specific antibody fragments are indicated for the treatment of known or strongly suspected life-threatening digoxin toxicity associated with ventricular arrhythmias or bradyarrhythmias unresposive to atropine sulfate, and when measures beyond the withdrawal of dixogin below and correction of any electrolyte abnormalities are considered necessary.

Digoxin specific antibody fragments (Digifab)
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Restricted Drug Restricted
Red SO
High Cost Medicine
  • Available as injection £££££
  • Very rarely needed and extremely expensive (~£1000 per vial and up to 30 vials may be needed!), discuss with the National Poisons Information Service 0344 892 0111
  • DigiFab® replaced Digibind® (Dec 2011)
 
Link  Toxbase: National Poisons Information Service
   
02.01.02  Phosphodiesterase type-3 inhibitors
02.02  Diuretics to top
 note 

Thiazides are used to relieve oedema due to chronic heart failure and, in lower doses, to reduce blood pressure.
Loop diuretics are used in pulmonary oedema due to left ventricular failure and in patients with chronic heart failure.
Combination diuretic therapy may be effective in patients with oedema resistant to treatment with one diuretic. Vigorous diuresis, particulalry with loop diuretics, may induce acute hypotension; rapid reduction of plasma volume should be avoided.

02.02.01  Thiazides and related diuretics
 note 

Thiazides and related compounds are moderately potent diuretics; they inhibit sodium reabsorption at the beginning of the distal convoluted tubule. They act within 1-2 hours of oral administration and most have a duration of action of 12 to 24 hours; they are usually administered early in the day so that the diuresis dose not interfere with sleep.
In the management of hypertension a low dose of a thiazide produces a maximal or near-maximal blood pressure lowering effect, with very little biochemical disturbance. Higher doses cause more marked changes in plasma potassium, sodium, uric acid, glucose and lipids, with little advantage in blood pressure control. Indapamide is the preferred diuretic in the management of hypertension, bendroflumethiazide can be used for mild or moderate heart failure; it is licensed for the treatment of hypertension but is no longer considered first line diuretic for this indication, although patients with stable and controlled blood pressure currently taking bendroflumethiazide can continue treatment. Metolazone is particularly effective when combined with a loop diuretic, used in heart failure. Profound diuresis can occur therefore careful monitoring is required and treatment is usually for short periods where possible.

Indapamide
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Formulary
  • Available as:
    • 2.5mg tablet (preferred) £
    • 1.5mg MR tablet £ (but more expensive than standard release)
 
   
Bendroflumethiazide
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Formulary
  • Available as tablets £
  • No longer recomended as first line for hypertension but in those patients who are currently stable with good blood pressure control it is ok to continue treatment
 
   
Metolazone
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Restricted Drug Restricted
Red SO
  • Available as tablets ££/50 tablets
  • Discontinued on the UK market in 2012 but unlicensed import available for use in secondary care
 
   
Chlorothiazide
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Restricted Drug Restricted
  • Available as 250mg/5ml suspension - restircted for paediatric use only £££/237mL bottle (unlicensed special)
 
   
02.02.02  Loop diuretics
 note 

Loop diuretics are used in pulmonary oedema due to left ventricular failure; IV administration produces relief of breathlessness and reduces pre-load sooner than would be expected from the time of onset of diuresis. Loop diuretics are also used in patients with chronic heart failure.
If necessary, a loop diuretic can be added to antihypertensive treatment to achieve better control of blood pressure in those with resistant hypertension, or in patients with impaired renal function or heart failure.
Loop diuretics can exacerbate diabetes (but hyperglycaemia is less likely than with thiazides) and gout.
Furosemide and bumetanide are similar in activity; both act within 1 hour of oral administration and diuresis is complete within 6 hours so that, if necessary, they can be given twice in one day without interfering with sleep. Following IV administration furosemide has a peak effect within 30 minutes. Both in normal subjects and in those with heart failure bumetanide has 80% bioavailability compared to 40% for furosemide, hence bumetanide is considered to be more effective in patients with heart failure.

Furosemide
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Formulary
  • Available as:
    • Tablet 20mg & 40mg  £ (all strengths)
    • Liquid 40mg/5mL & 50mg/5mL ££ (all strengths)
    • Injection 20mg/2mL £/10 ampoules, 50mg/5mL £/10 ampoules, 250mg/25mL ££/10 ampoules
  • IV doses of 40-80mg can be slow bolused, larger doses must be infused at a max rate of 4mg/min
 
   
Bumetanide
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Formulary
  • Available as:
    • Tablet 1mg £ & 5mg ££
    • Oral solution (extremely expensive) ££££/150mL bottle
  • Tablets disperse in water if needed (not licensed)
 
   
02.02.03  Potassium-sparing diuretics and aldosterone antagonists
 note 

Amiloride alone is a weak diuretic, it causes retention of potassium and are therefore given with thiazide or loop diuretics as a more effective alternative to potassium supplements.
Potassium supplements must not be given with potassium-sparing diuretics. Administration of a potassium-sparing diuretic to a patient receiving an ACE-i or an angiotensin-II receptor antagonist can also cause sever hyperkalaemia.

Amiloride
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Formulary
  • Available as:
    • Tablets £
    • Oral solution (expensive compared to tablets) ££/150mL
  • Tablets will disperse in water if needed (not licensed)
 
   
02.02.03  Aldosterone antagonists
 note 

Spironolactone potentiates thiazide or loop diuretics by antagonising aldosterone; it is a potassium sparing diuretic. Spironlactone is of value in the treatment of oedema and ascites caused by cirrhosis of the liver; furosemide can be used as an adjunct. Low doses of spironlactone are beneficial in moderate to severe heart failure and when used in resistant hypertension [unlicensed indication].
Eplerenone is licensed for use as an adjunct in left ventricular dysfunction with evidence of heart failure after a myocardial infarction; it is also licensed as an adjunct in chronic mild heart failure with left ventricular systolic dysfunction.
Potassium supplements must not be given with aldosterone antagonists.

Spironolactone
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First Choice
  • Available as:
    • Tablets 25mg, 50mg & 100mg £ (all strengths)
    • Oral solution £££/125mL bottle
 
Eplerenone
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Second Choice
Green SI
  • Available as tablets 25mg £ & 50mg ££ 
  • Second line agent if Spironlactone not tolerated
 
Link  NICE CG108: Chronic heart failure
   
02.02.04  Potassium-sparing diuretics with other diuretics to top
 note 

Although it is preferable to prescribe diuretics and potassium-sparing diuretics separately, the use of fixed combinations may be justified if compliance is a problem.

Co-amilofruse
(Furosemide and amiloride)
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Formulary
  • Available as tablets 2.5/20 & 5/40 ££ (both strengths)
 
   
02.02.05  Osmotic diuretics
 note 

Mannitol is an osmotic diuretic that can be used to treat cerebral oedema and raised intra-ocular pressure.

Mannitol
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Formulary
Red SO
  • Infusion 10% and 20% £/500mL bag
 
   
02.02.06  Mercurial diuretics
 note 

Mercurial diuretics are effective but are now almost never used because of their nephrotoxicity.

02.02.07  Carbonic anhydrase inhibitors
 note 

The carbonic anydrase inhibitor acetazolamide is a weak diuretic and is little used for its diuretic effect.

02.02.08  Diuretics with potassium
 note 

Many patients on diuretics do not need potassium supplements. For many of those who do, the amount of potassium in combined preparations may not be enough, and for this reason their use is to be discouraged.

02.03  Anti-arrhythmic drugs to top
02.03.01  Management of arrhythmias
 note 

Management of an arrhythmia requires preciese diagnosis of the type of arrhythmia, and electrocardiography is essential; underlying causes such as heart failure require appropriate treatment.

Treatment of patients with AF aims to reduce symptoms and prevent complications, especially stroke. All patients with AF should be assessed for thier risk of stroke and thromboembolism. AF can be managed by either controlling the ventricular rate ('rate control') or by attempting to restore and maintain synus rhythm ('rhythm control'). If drug treatment fails to control the symptoms of AF or is unsuitable, ablation strategies can be considered. Review anticoagulation, stroke, and bleeding risk at least anually in all patients with AF.

02.03.02  Drugs for arrhythmias
 note 

Anti-arrhythmic drugs can be classified clinically into those that act on supraventricular arrhythmias (e.g. verapamil hydrochloride), those that act on both supraventricular and ventricular arrhythmias (e.g. amiodarone hydrochloride) and those that act on ventricular arrhythmias (e.g. lidocaine hydrochloride).

Anti-arrhythmic drugs can also be classified according to their effects on the electrical behaviour of myocardial cells during activity, although this classification is of less clinical significance:

- Class I: membrane stabilising drugs (e.g. lidocaine, flecainide)
- Class II: beta-blockers
- Class III: amiodarone; sotalol (also Class II)
- Class IV: calcium-channel blockers (included verapamil but not   dihyropyridines)

The negative inotropic effects of anti-arrhythmic drugs tend to be additive. Therefore special care should be taken if two or more are used, especially if myocardial function is impaired. Most drugs that are effective in countering arrhythmias can also provoke them in some circumstances; moreover, hypokalaemia enhances the pro-arrhythmic effect of many drugs.

02.03.02  Supraventricular arrhythmias
Adenosine
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Formulary
Red SO
  • Available as injection 6mg/2mL ££/6 ampoules
 
   
Dronedarone
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Formulary
Amber SC
  • Available as tablets £££
  • Dronedarone should be initiated by a sepcialist in line with NICE TA197, after the patient is stabilised on treatment, prescribing may be continued in primary care under shared care arrangements
  • Due to its safety profile, dronedarone should only be prescribed after alternative treatment options have been considered
 
Link  Dronedarone - shared care agreement
Link  APC - drug positioning statement
Link  NICE TA197: Dronedarone for the treatment of non-permanent atrial fibrillation
   
02.03.02  Supraventricular and ventricular arrhythmias
Amiodarone
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Formulary
Green SA
  • Available as:
    • Tablets 100mg & 200mg £/28 tablets (both strengths)
    • Injection 150mg/3mL ££/10 ampoules
    • Injection 300mg/10mL (cardiac boxes) ££/pre-filled syringe
 
Link  Drug safety update - Simeprevir with sofosbuvir: risk of severe bradycardia and heart block when taken with amiodarone
Link  Drug safety update - Sofosbuvir with daclatasvir; sofosbuvir and ledipasvir: risks of severe bradycardia and heart block when taken with amiodarone
   
Flecainide
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Formulary
Green SA
  • Available as:
    • Tablets 50mg £/60 tablets & 100mg ££/60 tablets
    • Injection  ££/5 ampoules
 
   
Propafenone
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Formulary
Amber SC
  • Available as tablets 150mg ££/90 tablets
 
Link  Propafenone - shared care agreement
   
02.03.02  Ventricular arrhythmias to top
Lidocaine
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Formulary
Red SO
  • Available as injection
 
   
02.04  Beta-adrenoceptor blocking drugs
 note 

Beta-adrenoceptor blocking drugs (beta-blockers) block the beta-adrenoceptors in the heart, peripheral vasculature, bronchi, pancreas, and liver. Many beta-blockers are now available and in general they are all equally effective. There are, however, differences between them, which may affect choice in treating particular diseases or individual patients.

Atenolol
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Formulary
  • Available as:
    • Tablets 25mg, 50mg & 100mg £/28 tablets (all strengths)
    • Oral solution 25mg/5mL ££/300mL
    • Injection 5mg/10mL ££/10 ampoules
 
   
Bisoprolol
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Formulary
  • Available as tablets 1.25mg, 2.5mg, 3.75mg, 5mg & 10mg £/28 tablets
 
   
Carvedilol
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Formulary
  • Available as tablets 3.125mg, 12.5mg & 25mg £/28 tablets
 
   
Labetalol
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Formulary
  • Available as:
    • Tablets 100mg £/56 tablets & 200mg ££/56 tablets 
    • Injection 100mg/20mL £££/5 ampoules
 
   
Metoprolol
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Formulary
  • Available as:
    • Tablets 50mg & 100mg £/28 tablets
    • Injection 5mg/5mL ££/5 ampoules
 
   
Nebivolol
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Formulary
  • Available as tablets 5mg £/28 tablets
 
   
Propranolol
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Formulary
  • Available as:
    • Tablets 10mg (28), 40mg (28) & 80mg (56) £ (for all strengths)
    • MR capsule 80mg & 160mg £/28 tablets
    • Injection 1mg/1mL ££/10 ampoules
    • Oral solution 5mg/5mL & 50mg/5mL ££/150mL bottle (both strengths)
 
   
Sotalol
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Formulary
Green SI
  • Available as tablets 40mg & 80mg £/28 tablets (both strengths)
 
   
02.05  Drugs affecting the renin-angiotensin system and some other antihypertensive drugs
02.05.01  Vasodilator antihypertensive drugs
 note 

Vasodilators have a potent hypotensive effect, especially when used in combination with a beta-blocker and a thiazide.
Hydralazine hydrochloride is given by mouth as an adjunct to other antihypertensives in the treatment of resistant hypertension but is rarely used; when used alone it causes tachycardia and fluid retention.
Sildenafil is licensed for the treatment of pulmonary arterial hypertension and should be used under specialist supervision.

Hydralazine
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Formulary
  • Available as a tablet 25mg & 50mg ££/56 tablets
  • May be used in combination with a nitrate in the management of heart failure in patients who are intolerant of ACE inhibitors
 
   
Controlled Drug Sildenafil
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Restricted Drug Restricted
  • Generic sildenafil tablets (unlicensed indication): for dose escalation 25mg-100mg three times daily £/4 tablets (25mg, 50mg & 100mg)
  • As Revatio tablets: for use onlly at licensed dose of 20mg three times daily ££££/90 tablets (20mg)
 
Link  Targeted therapies for use in pulmonary hypertension in adults
   
02.05.02  Centrally acting antihypertensive drugs
 note 

Methyldopa is a centrally acting antihypertensive; it may be used for the management of hypertension in pregnancy.
Moxonidine, a centrally acting drug, is licensed for mild to moderate essential hypertension. It may have a role when thiazides, calcium-channel blockers, ACE inhibitors, and beta-blockers are not appropriate or have failed to control blood pressure.

Methyldopa
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Second Choice
  • Available as tablet 250mg ££/56 tablets
  • Should only be used for hypertension when other agents have failed or aren't suitable
 
   
Moxonidine
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Formulary
  • Available as tablets 200mcg, 300mcg & 400mcg £/28 tablets (all strengths)
  • Should only be used for hypertension when other agents have failed or aren't suitable
 
   
02.05.03  Adrenergic neurone blocking drugs to top
 note 

Adrenergic neurone blocking drugs prevent the release of noradrenaline from postganglionic adrenergic neurones. These drugs do not control supine blood pressure and may cause postural hypotension. For this reason they have largely fallen from use, but may be necessary with other therapy in resistant hypertension.
Guanethidine monosulfate, which also depletes the nerve endings of noradrenaline, is licensed for rapid control of blood pressure, however, alternative treatments are preferred. 

02.05.04  Alpha-adrenoceptor blocking drugs
 note 

Alpha-blockers can be used with other antihypertensive drugs in the treatment of resistant hypertension.

Doxazosin
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Formulary
  • Available as:
    • tablets 1mg, 2mg & 4mg £/28 tablets
    • MR tablets 4mg ££/28 tablets
  • Doxazosin may be used as a 4th line option in the management of hypertension when control has not been achieved with other agents
  • MR tablets should be reserved for initiation by a specialist in patients with difficult to treat hypertension who are unable to tolerate immediate release tablets
 
Link  UKMI Q&A: How should conversion between doxazosin formulations be carried out?
   
02.05.05  Drugs affecting the renin-angiotensin system
 note 

Combination therapy with two drugs affecting the renin-angiotensin system (ACE inhibitors, angiotensin-II receptor antagonists, and aliskiren) is not recommended due to an increased risk of hyperkalaemia, hypotension, and renal impairment, compared to use of a single drug. Patients with diabetic nephropathy are particularly susceptible to developing hyperkalaemia and should not be given an ACE inhibitor with an angiotensin-II receptor antagonist. There is some evidence that the benefits of combination use of an ACE inhibitor with candesartan or valsartan may outweigh the risk in selected patients with heart failure for whom other treatments are unsuitable. For patients currently taking combination therapy, the need for continued combined therapy should be reviewed. If combination therapy is considered essential, it should be carried out under specialist supervision, with close monitoring of blood pressure, renal function and electrolytes (particularly potassium).

02.05.05.01  Angiotensin-converting enzyme inhibitors (ACE inhibitors)
 note 

ACE inhibitors inhibit the conversion of antiotensin I to angiotensin II. They have many uses and are generally well tolerated.

Renal effects
Renal function and electrolytes should be checked before starting ACE inhibitors (or increasing the dose) and monitored during treatment (more frequently if features mentioned below present); hyperkalaemia and other side effects of ACE inhibitors are more common in those with impaired renal function and the dose may need to be reduced. Although ACE inhibitors now have a specialised role in some forms of renal disease, including chronic kidney disease, they also occasionaly cause impairment of renal function which may progress and become severe in other circumstances (at particular risk are the elderly).
Concomitant treatment with NSAIDs increases the risk of renal damage, and potassium-sparing diuretics (or potassium-containing salt substitutes) increase the risk of hyperkalaemia.
ACE inhibitors are best avoided in patients with known or suspected renovascular disease, unless the blood pressure cannot be controlled by other drugs. If ACE inhibitors are used, they should be initiated only under specialist supervision and renal fucntion should be monitored regularly.

Concomittant diuretics
ACE inhibitors can cause a very rapid fall in blood pressure in volume-depleted patients; treatment should therefore be initiated with very low doses. If the dose of diuretic is greater than furosemide 80mg furosemid or equivalent, the ACE inhibitor should be initialted under close supervision and in some patients the diuretic dose may be need to be reduced or the diuretic discontinued at least 24 hours beforehand (may not be possible in heart failure due to risk of pulmonary oedema). If high-dose diuretic therapy cannot be stopped, close observation is recommended after administration of the first dose of ACE inhibitor, for at least 2 hours or until the blood pressure has stabilised.

Ramipril
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First Choice
  • Available as capsules 1.25mg, 2.5mg, 5mg & 10mg £/28 capsules (all strengths)
 
Lisinopril
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Formulary
  • Available as tablets 2.5mg, 5mg, 10mg & 20mg £/28 tablets (all strengths)
 
   
Perindopril erbumine
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Formulary
  • Available as tablets 2mg & 4mg £/28 tablets (all strengths)
 
   
02.05.05.02  Angiotensin-II receptor antagonists
 note 

Angiotensin-II receptor antagonists have many properties similar to those of the ACE inhibitors, however, unlike ACE inhibitors, they do not inhibit the breakdown of bradykinin and other kinins, and thus are less likely to cause the presistent dry cough which can complicate ACE inhibitor therapy. They are therefore a useful alternative for patients who have to discontinue and ACE inhibitor because of persistent cough.
(See Renal effects under Angiotensin-converting enzyme inhibitors, above).

Losartan
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First Choice
  • Available as tablets 25mg, 50mg & 100mg £/28 tablets (all strengths)
 
Candesartan
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Formulary
  • Available as tablets 2mg (7), 4mg (28) & 8mg (28) £ all strengths
 
   
Irbesartan
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Formulary
  • Available as tablets 75mg, 150mg & 300mg £/28 tablets (all strengths)
  • 2nd line agent for Type 2 diabetics who have not tolerated ACEi
 
   
Valsartan
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Formulary
  • Available as capsules 40mg & 80mg £/28 (both strengths)
 
   
Valsartan with sacubitril (Entresto)
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Formulary
Green SI
  • Available as tablets 24/26 ££/28 tablets, 49/51 ££/28 tablets & 97/103 £££/56 tablets
  • Entresto® tablets contain valsartan and sacubitril; the proportions are expressed in the form x/y where x and y are the strength in milligrams of valsartan and sacubitril respectively.
  • Valsartan, in this formulation is more bioavailable than other tablet formulations - 26mg, 51mg and 103mg valsartan is equivalent to 40mg, 80mg and 160mg, respectively.
  • Furthermore, note that the 26/24mg, 51/49mg and 103/97mg strengths are sometimes refered to as a total of both drug strengths, that is, 50mg, 100mg and 200mg respectively.
 
Link  Entresto - Drug Positioning Statement
Link  Entresto - Specialist Inititated Drug Checklist
Link  NICE TA388: Sacubitril valsartan for treating symptomatic chronic heart failure with reduced ejection fraction
   
02.06  Nitrates, calcium-channel blockers, and potassium-channel activators to top
02.06.01  Nitrates
 note 

Nitrates have a useful role in angina. Although they are potent coronary vasodilators, their principal benefit follows from a reduction in venous return which reduces left ventricular work. Unwanted effects such as flushing, headache, and postural hypotension may limit therapy, especially when angina is severe or when patients are unusually sensitive to the effects of nitrates.
Sublingual glyceryl trinitrate is one of the most effective drugs for providing rapid symptomatic relief of angina, but its effect lasts only for 20-30 minutes. Duration of action may be prolonged by transdermal preparations (but tolerance may develop).

Tolerance
Many patients on long-acting or transdermal nitrates rapidly develop tolerance (with reduced therapeutic effects). Reduction of blood-nitrate concentrations to low levels for 4 to 12 hours each day usually maintains effctiveness in such patients. To avoid tolerance transdermal patches should be left off for 8-12 hours (usually overnight) in each 24 hours; in the case of conventional formulations isosorbide mononitrate, the second of the two daily doses should be given after about 8 hours rather than after 12 hours. Conventional formulations of isosorbide mononitrate should not usually be given more than twice daily unless small doses are used; modified-release formulations of isosorbide mononitrate should nly be given once daily, and used in this way do not produce tolerance.

Glyceryl Trinitrate
(Injection)
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Formulary
Red SO
  • Available as injection 5mg/5ml ££/10 ampoules & 50mg/50mL ££/1 vial
 
   
Glyceryl Trinitrate
(sublingual spray)
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Formulary
  • Available as sublingual spray £/200 dose
 
   
Glyceryl Trinitrate
(Transdermal patches)
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Formulary
  • Available as patches 5mg/24 hour & 10mg/24 hour ££/28 patches (both strengths)
  • To be used when the patient is nil by mouth
 
   
Isosorbide Mononitrate
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Formulary
  • Available as:
    • tablets 10mg & 20mg £/56 tablets
    • MR tablets/capsules (preferred)
  • Short acting preparations should be prescribed asymmetrically to avoid nitrate tolerance
 
   
02.06.02  Calcium-channel blockers
 note 

Calcium-channel blockers differ in their predilection for the various possible sites of action and, therefore, their therapeutic effects are disparate. There are important differences between verapamide hydrochloride and diltiazem hydrochloride and the dihyropyridine calcium-channel blockers.

Dihydropyridines (e.g. nifedipine, amlodipine, lercanidipine)
Primarily cause smooth muscle relaxation and therefore decrease vascular resistance and consequently lowers arterial blood pressure.
Adverse effects include; headache and flushing, peripheral oedema (particularly with rapid onset short acting agents).

Non dihydropyridines (e.g. verapamil)
Primarily used as anti-anginals and anti-arrhytmics, more selective for cardiac tissue than smooth muscle. May be used for angiina as reduced heart rate and contractility. Also impairs AV node conduction therefore may be some for some arrhythmias. Should be avoided in heart failure because it depressed cardiac function. Adverse effets include constipatin, bradycardia, heart block.

Benzothiazepine derivative (e.g. diltiazem)
Have less negative inotopic effect than verapamil bus also have significan myocardial depression, thus should be avoided in heart failure. Adverse effects include bradycardia, AV block, palpitations. Different versions of modified release preparations containing more that 60mg diltiazem may not have the same clinical effect. To avoid confusion between different formulations prescribers should specify the brand to be dispensed.

Amlodipine
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First Choice
  • Available as tablets 5mg & 10mg £ (both strengths)
 
Diltiazem
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Second Choice
  • Available as tablets/capsules
  • Once daily preparations are preferred
  • Prescribers should specify the brand to be dispensed, different versions of modified release preparations containing more than 60mg diltiazem may not have the same clinical effect - contact pharmacy for most cost-effective brand
 
   
Lercanidipine
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Second Choice
  • Available as tablets 10mg £
  • 2nd line after amlodipine
 
   
Nifedipine
View adult BNF View SPC online View childrens BNF  Track Changes
Formulary
  • Available as tablets/capsules
  • Contact pharmacy for advice on prescribing most cost-effective brand
 
   
Verapamil
View adult BNF View SPC online View childrens BNF  Track Changes
Formulary
  • Available as:
    • tablets 40mg (84), 80mg (84) and 120mg (28) £/all strengths 
    • MR tablets 120mg & 240mg ££/both strengths
    • injection (specialist only) 5mg/2mL ££/5 vials
 
Link  UKMI Q&A: Evidence for verapamil for cluster headache
   
Nimodipine
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Formulary
Red SO
  • Available as:
    • injection
    • tablets 30mg ££/100 tablets
  • Unlicensed use for chronic fatigue patients approved at GEH for use by endocrine consultants
 
   
02.06.03  Other anitanginal drugs
 note 

Nicorandil, a potassium-channel activator with a nitrate component, has both arterial and venous vasodilating properties and is lecensed for the prevention and long-term treatment of angina. Nicorandil has similar efficacy to other antianginal drugs in controlling symptoms; it may produce additional symptomatic benefit in combination with other antianginal drugs [unlicensed indication].

Ivabradine lowers the heart rate by its action on the sinus node. It is licensed for the treatment of angina in patients who are in normal sinus rhythm in combination with a beta-blocker, or when beta-blockers are contra-indicated or not tolerated. Ivabradine, in combination with standard therapy including a beta-blocker (unless contra-indicated or not toelrated), is also licensed for mild to severe stable chronic heart failure in patients who are in sinus rhythm.

Ranolazine is licensed as adjunctive therapy in patients who are inadequately controlled or intolerant of first-line antianginal drugs.

Nicorandil
View adult BNF View SPC online View childrens BNF  Track Changes
Formulary
  • Available as tablets 10mg £/60 tablets & 20mg ££/60 tablets
 
Link   MHRA drug safety update Nov 2015 risk of serious skin, mucosal, and eye ulceration, gastrointestinal ulcers which may progress to perforation, haemorrhage, fistula, or absces
   
Ivabradine
View adult BNF View SPC online View childrens BNF  Track Changes
Formulary
  • Available as tablets 5mg ££/56 tablets & 7.5mg £££/56 tablets
  • Manufacturer advises reduce initial dose to 2.5mg twice daily with concurrent use of moderate CYP3A4 inhibitors (except diltiazem, erythromycin and verapamil where concurrent use is contra-indicated)
 
Link  NICE TA267: Ivabradine for treating chronic heart failure
   
Ranolazine (Ranexa)
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Formulary
  • Available as MR tablets 375mg & 500mg ££/60 tablets (both strengths)
  • Add-on therapy for the treatment of angina who are inadequately controlled or intolerant to first-line antianginal therapies
 
Link  NICE CG126: Guidance on Stable Angina
   
02.06.04  Peripheral vasodilators and related drugs
02.07  Sympathomimetics to top
02.07.01  Inotropic sympathomimetics
Dobutamine
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Formulary
Red SO
  • Available as injection 250mg/20mL ££/5 vials
 
   
Dopamine
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Formulary
Red SO
  • Available as injection
 
   
02.07.02  Vasoconstrictor sympathomimetics
Metaraminol
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Restricted Drug Restricted
Red SO
  • Available as injection 10mg/1mL ££/10 ampoules
 
   
Noradrenaline / Norepinephrine
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Restricted Drug Restricted
Red SO
  • Available as injection 8mg/8mL £££/10 ampoules
 
   
02.07.03  Cardiopulmonary resuscitation
Adrenaline / Epinephrine
View adult BNF View SPC online View childrens BNF  Track Changes
Formulary
  • Available as injection
 
   
02.08  Anticoagulants
 note 

The main use of anticoagulants is to prevent thrombus formation or extension of an existing throbmus in the slower-moving venous side of the circulation, where the thrombus consists of a fibrin web enmeshed with platelets and red cells.
Anticoagulants are of less use in preventing thrombus formation in arteries, for in faster flowing vessels thrombi are composed mainly of platelets with little fibrin.

02.08.01  Parenteral anticoagulants to top
Anticoagulant Citrate Dextrose Solution (ACD-A)
 Track Changes
Restricted Drug Restricted

ACD-A is in a pre-made infusion bag and therefore does not have to be prepared in comparison to Heparin.

Reduced cost in comparison to Heparin Saline

Reduces human error as the product does not have to be prepared before use.

Reduces risk of needlestick injury

Can be used in patients where Heparin in contraindicated

Reduced risk of bleeding

Can be used in patients where systemic anticoagulationis contra-indicated

 

 
   
02.08.01  Heparin
 note 

Heparin initiates anticoagulation rapidly but has a short duration of action. It is often referred to as 'standard' or heparin (unfractionated) to distinguish it from the low molecular weight heparins, which have a longer duration of action. Although a low molecular weight heparin is generally preferred for routine use, heparin (unfractionated) can be used in those at high risk of bleeding because its effect can be terminated rapidly by stopping the infusion.

Heparin
View adult BNF View SPC online View childrens BNF  Track Changes
Formulary
  • Available as injection
 
   
02.08.01  Low molecular weight heparins
 note 

Low molecular weight heparins are usually preferred over heparin (unfractionated) in the prevention of venous thromboembolism because they are as effective and they have a lower risk of heparin-induced thrombocytopenia. The duration of action of low molecular weight heparins is longer than that of heparin (unfractionated) and once-daily subcutaneous administration is possible for some indications, making them convenient to use.

Enoxaparin (Clexane or Inhixa)
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Formulary
  • Available as injection
    • 20mg/0.2mL ££/10 injections
    • 40mg/0.4mL ££/10 injections
    • 60mg/0.6mL ££/10 injections
    • 80mg/0.8mL £££/10 injections
    • 100mg/1mL £££/10 injections
    • 120mg/0.8mL £££/10 injections
    • 150mg/1mL £££/10 injections
  • Clexane is the brand of choice, Inhixa a biosimilar is used when there are stock shortages of Clexane
 
   
02.08.01  Heparin flushes
 note 

The use of heparin flushes should be kept to a minimum. For maintaining patency of peripheral venous catheters, sodium chloride injection 0.9% is as effective as heparin flushed. The role of heparin flushes in maintaining patency of arterial and central venous catheters is unclear.

Heparin
(flush)
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Formulary  
   
02.08.01  Epoprostenol
 note 

Epoprostenol (protacyclin) can be given to inhibit platelet aggregation during renal dialysis when heparins are unsuitable or contra-indicated. It has a short half-life of approximately 3 minutes and therefore it must be administered via continuous IV infusion. 

Epoprostenol
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Formulary
Red SO
  • Available as injection 500mcg ££/1 vial
 
   
02.08.01  Fondaparinux to top
 note 

Fondaparinux sodium is a synthetic pentasaccharide that inhibits activated factor X. It has been used occasionally when patients have been found to have an allergic reaction to LMWH.

Fondaparinux
View adult BNF View SPC online View childrens BNF  Track Changes
Restricted Drug Restricted
  • Available as injection
    • 1.5mg/0.3mL £££/10 injections
    • 2.5mg/0.5mL £££/10 injections
    • 7.5mg/0.6mL ££££/10 injections
  • To be used when Enoxaparin unsuitable/not tolerated
 
   
02.08.02  Oral anticoagulants
Warfarin
View adult BNF View SPC online View childrens BNF  Track Changes
Formulary
  • Available as tablets 1mg & 3mg £/28 tablets (both strengths)
  • At GEH we use only 1mg and 3mg tablets
 
Link  UKMI Q&A: IM injections in warfarin patients
Link  UKMI Q&A: Warfarin and PPI interaction
   
Rivaroxaban (Xarelto)
View adult BNF View SPC online View childrens BNF  Track Changes
Formulary
  • Available as tablets 10mg ££/10 tablets, 15mg £££/28 tablets & 20mg £££/28 tablets
  • Indications
    • Stroke prevention in AF (SIDC to be completed and faxed to GP surgery)
    • Treatment and prevention of thromboembolic events (SIDC to be completed and faxed to GP surgery)
    • Prophylaxis of VTE post hip and knee replacement surgery (complete course to be supplied by hospital)
 
Link  Specialist Initiated Drug Checklist
Link  NICE TA170: Rivaroxaban for the prevention of venous thromboembolism after total hip or total knee replacement in adults
Link  NICE TA256: Rivaroxaban for the prevention of stroke and systemic embolism in people with atrial fibrillation
Link  NICE TA261: Rivaroxaban for the treatment of deep vein thrombosis and prevention of recurrent deep vein thrombosis and pulmonary embolism
Link  NICE TA287: Rivaroxaban for treating pulmonary embolism and preventing recurrent venous thromboembolism
   
Apixaban (Eliquis)
View adult BNF View SPC online View childrens BNF  Track Changes
Formulary
  • Available as tablets 2.5mg £££/60 tablets & 5mg ££/28 tablets
  • Indications
    • Stroke prevention in AF (SIDC to be completed and faxed to GP surgery)
    • Treatment and prevention of thromboembolic events (SIDC to be completed and faxed to GP surgery)
 
Link  Specialist Initiated Drug Checklist
Link  NICE TA275: Stroke and systemic embolism (prevention, non-valvular atrial fibrillation) - apixaban
Link  NICE TA245: Apixaban for the prevention of venous thromboembolism after total hip or knee replacement in adults
Link  NICE TA341: Apixaban for the treatment and secondary prevention of deep vein thrombosis and/or pulmonary embolism
   
Dabigatran (Pradaxa)
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Formulary
Green SA
  • Available as capsules 110mg £££/60 capsules & 150mg £££/60 capsules
  • Indications
    • Stroke prevention in AF (SIDC to be completed and faxed to GP surgery)
    • Treatment and prevention of thromboembolic events (SIDC to be completed and faxed to GP surgery)
    • Prophylaxis of VTE post hip and knee replacement surgery (complete course to be supplied by hospital)
 
Link  Specialist Initiated Drug Checklist
Link  NICE TA157: Dabigatran etexilate for the prevention of venous thromboembolism after hip or knee replacement surgery in adults
Link  NICE TA249: Dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation
Link  NICE TA327: Dabigatran etexilate for the treatment and secondary prevention of deep vein thrombosis and/or pulmonary embolism
   
Edoxaban (Lixiana)
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Formulary
Green SA
  • Available as tablets 30mg ££/28 tablets & 60mg ££/28 tablets
  • Indications
    • Stroke prevention in AF (SIDC to be completed and faxed to GP surgery)
    • Treatment and prevention of thromboembolic events (SIDC to be completed and faxed to GP surgery)
 
Link  Specialist Initiated Drug Checklist
Link  NICE TA354: Edoxaban for treating and for preventing deep vein thrombosis and pulmonary embolism
Link  NICE TA355: Edoxaban for preventing stroke and systemic embolism in people with non-valvular atrial fibrillation
   
02.08.02  Antidotes
Idarucizumab (Praxbind)
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Restricted Drug Restricted
Red SO
  • Available as injection £££££/2 vials
  • Reversal agent for dabigatran
  • ~ £1000 per dose
  • On advice from consultant haematologist
 
   
02.08.03  Protamine sulphate
 note 

If haemorrhage occurs it is usually sufficient to withdraw unfractionated or low molecular weight heparin, but if rapid reversal of the effects of the heparin is required, protamine sulfate is a specific antidote (but only partially reverses the effects of low molecular weight heparins).

Protamine Sulfate
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Formulary
Red SO
  • Available as injection 50mg/5mL ££/10 ampoules
 
   
02.09  Antiplatelet drugs
 note 

Antiplatelet drugs decrease platelet aggregation and inhibit thrombus formation in the arterial circulation, because in faster-flowing vessels, thrombi are composed maily of platelets with little fibrin.

Use of aspirin in primary prevention of cardiovascular events, in patients with or without diabetes, is of unproven benefit. Long-term use of aspirin is of benefit in established cardiovascular disease (secondary prevention); unduly high blood pressure must be controlled before aspirin is given. If the patient is at high risk of gastro-intestinal bleeding, a proton pump inhibitor can be added.

Prescribing for secondary prevention should be in line with GEH guidelines.

Aspirin
(antiplatelet)
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Formulary
  • Available as:
    • Dispersable tablets 75mg (preferred) £/28
    • Enteric coated 75mg £/56
    • Suppositories 150mg ££/10
 
Link  UKMI Q&A: Can a person with low dose aspirin take gingko?
Link  UKMI Q&A: Is there evidence to support the use of EC coated aspirin to reduce GI side effects?
   
Clopidogrel
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Formulary
  • Available as tablets £/28
 
Link  NICE TA80: Acute coronary syndromes - clopidogrel
Link  NICE TA210: Clopidogrel and modified-release dipyridamole for the prevention of occlusive vascular events
   
Dipyridamole
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Formulary
  • Available as 200mg MR capsules ££/60
 
   
Prasugrel (Efient)
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Restricted Drug Restricted
Green SI
  • Available as tablets ££/28
  • For initiation by cardiology team
 
Link  NICE TA182: Acute coronary syndrome - prasugrel
Link  NICE TA317: Prasugrel with percutaneous coronary intervention for treating acute coronary syndromes (review of technology appraisal guidance 182)
   
Ticagrelor (Brilique)
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Restricted Drug Restricted
Green SI
  • Available as tablets £££/56
  • For initiation by cardiology team
 
Link  NICE TA236: Ticagrelor for the treatment of acute coronary syndromes
Link  NICE TA420: Ticagrelor for preventing atherothrombotic events after myocardial infarction
   
02.10  Stable angina, acute coronary syndromes, and fibrinolysis to top
02.10.01  Management of stable angina and acute coronary syndromes
 note 

STABLE ANGINA 

Usually results from atherosclerotic plaques in the coronary arteries that restrict blood flow and oxygen supply to the heart; it is often precipitated by exertion and relieved by rest. Treatment involves management of acute anginal pain, and long term management to prevent angina attacks and to reduce the risk of cardiovascular events.

ACUTE CORONARY SYNDROMES

Acute coronary syndromes encompass a spectrum of conditions which include unstable angina, and myocardial infarction with or without ST-segment elevation. Patients with different acute coronary syndromes may present similarly; definitive diagnosis is made on the basis of clinical presentation, ECG changes, and measurement of biochemical cardiac markers.

Unstable angina and non-ST-segment elevation myocardial infarction (NSTEMI)

These are related acute coronory symptoms that fall between the classifications of stable angina and STEMI. They usually occur as a result of atheromatous plaque rupture, and are often characterised by stable angina that suddenly worsens, recurring or prolonged angina at rest, or new onset of severe angina. Patients with unstable angina have no evidence of myocardia necrosis, whereas in NSTEMI, myocardial necrosis (less significant than with STEMI) will be evident. There is risk of progression to STEMI or sudden death, particularly in patients who experience pain at rest.

ACS bundle

ST-segment elevation myocardial infarction (STEMI)

This is an acute coronary syndrome where atheromatous plaque rupture leads to thrombosis and myocardial ischaemia, with irreversible necrosis of the heart muscle, often leading to long-term complications. STEMI can also occasionally occur as a result of coronary spasm or embolism, arteritis, spontaneous thrombosis, or sudden severe elevation in blood pressure.

Primary PCI assessment for STEMI patients

 

02.10.02  Fibrinolytic drugs
 note 

The value of thrombolytic drugs for the treatment of myocardial infarction has been established. Thrombolytic drugs are indicated for any patient with acute myocardial infarction for whom the benefit is likely to outweigh the risk of treatment. Patients should not be denied thrombolytic treatment on account of age alone because mortality in the elderly is high and the reduction in mortality is the same as in younger patients.

Alteplase
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Formulary
Red SO
  • Available as injection 10mg & 50mg ££££/vial (both strengths)
 
Link  Alteplase for PE rota
Link  Alteplase for STEMI rota
   
Streptokinase
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Formulary
Red SO
 
   
Urokinase
View adult BNF View SPC online View childrens BNF  Track Changes
Formulary
Red SO
  • Available as injection:
    • 10000 units ££/vial
    • 25000 units ££/vial
    • 100000 units £££/vial
 
   
02.11  Antifibrinolytic drugs and haemostatics
 note 

Fibrin dissolution can be impaired by the administration of tranexamic acid, which inhibits fibrinolysis. It can be used to prevent bleeding or to treat bleeding associated with excessive fibrinolysis (e.g. in surgery, dental extraction, obstetric disorders) and in the managment of menorrhagia.

Tranexamic Acid
View adult BNF View SPC online View childrens BNF  Track Changes
Formulary
  • Available as:
    • tablets ££/60
    • injection ££/10 ampoules
 
Link  NICE guideline on heavy menstrual bleeding
   
02.11  Blood-related products
 note  Stocked by pathology.
02.12  Lipid-regulating drugs to top
02.12  Bile acid sequestrants
 note 

Bile acid sequestrants effectivley reduce LDL-cholesterol but can aggravate hypertriglyceridaemia. Treatment with bile acid sequestrants may be appropriate under specialist supervision if statins and ezetimibe are inappropriate, and when LDL-cholesterol is severely raised, for example n familial hypercholesterolaemia.

Colestyramine (Questran Light)
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Formulary
  • Available as sugar free sachets ££/50
 
   
02.12  Ezetimibe
 note 

Ezetimibe inhibits intestinal absorption of cholesterol. It has a limited role though may be used as monotherapy where there is statin intolerance or as an adjunct when target lipid levels are not reached despite escalated statin l
or for use in familial hyper cholesterolaemia, when target lipid levels are not reached despite dietary control and maximum tolerated statin. If used alone, it has a modest effect on lowering LDL-cholesterol, with little effect on other lipoproteins.

Ezetimibe (Ezetrol)
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Formulary
  • Available as tablet £/28
 
Link  NICE TA385: Ezetimibe for treating primary heterozygous-familial and non-familial hypercholesterolaemia
   
02.12  Fibrates
 note 

Fibrates may be of benefit in those with mixed hyperlipidaemia and low HDL-cholesterol.
They should be used first line in severe hypertriglyceridaemia which should be confirmed with fasting blood lipid levles. Secondary causes (alcohol, obesity, drugs) should be excluded as well as familial causes.
Fibrates have a variable effect on LDL-cholesterol and are indicated only if there is statin intolerance or when triglycerides are still elevated despite LDL lowering to target or if triglycerides>10mmmol/litre, (>2.3mmol/l in patients with diabetes).
Co-prescription of fenofibrate with a statin should be reserved for patients with severe combined dyslipidaemia and high cardiovascular risk without any history of muscular disease. Transaminase levels should be monitored every 3 months for the first year.

Fenofibrate
View adult BNF View SPC online View childrens BNF  Track Changes
Formulary
  • Available as tablets/capsules
 
   
02.12  Statins
 note 

Statins are more effective than other lipid-regulating drugs at lowering LDL-cholesterol concentration but they are less effective than the fibrates in reducing triglyceride concentration. However, statins reduce cardiovascular disease events and total mortality irrespective of the initial cholesterol concentration.
Statins work by inhibiting the enzyme HMG-Co Enzyme A reductase, they require at least one to two weeks to become effective and four to six weeks to exert thier full effect.

 

Rosuvastatin Atorvastatin Simvastatin
- - 10mg
- 10mg 20mg
5mg 20mg 40mg
10mg 40mg 80mg
20mg 80mg -
40mg - -

 

Atorvastatin
View adult BNF View SPC online View childrens BNF  Track Changes
Formulary
  • Available as tablets 10mg,20mg,40mg,80mg £/28 all strengths
 
   
Simvastatin
View adult BNF View SPC online View childrens BNF  Track Changes
Formulary
  • Available as tablets 10mg,20mg,40mg,80mg £/28 all strengths
 
   
Rosuvastatin
View adult BNF View SPC online View childrens BNF  Track Changes
Restricted Drug Restricted
  • Available as tablets 5mg, 10mg, 20mg, 40mg £/28 all strengths (but more expensive than other two statins on the formulary)!
  • May be considered if other preferred statins are not suitable
 
   
02.12  Omega-3 fatty acid compounds to top
 note 

There is no evidence that omega-3 fatty acid compounds reduce the risk of cardiovascular disease.

02.12  Other
Evolocumab (Repatha)
View adult BNF View SPC online View childrens BNF  Track Changes
Formulary
Red SO
BlueTeq
  • Available as injection 140mg/mL £££/2 pens
 
Link  NICE TA394: Evolocumab for treating primary hypercholesterolaemia and mixed dyslipidaemia
   
 ....
Key
note Notes
Section Title Section Title (top level)
Section Title Section Title (sub level)
First Choice Item First Choice item
Non Formulary Item Non Formulary section
Restricted Drug
Restricted Drug
Unlicensed Drug
Unlicensed
Track Changes
Display tracking information
click to search medicines.org.uk
Link to adult BNF
click to search medicines.org.uk
Link to children's BNF
click to search medicines.org.uk
Link to SPCs
SMC
Scottish Medicines Consortium
Cytotoxic Drug
Cytotoxic Drug
CD
Controlled Drug
High Cost Medicine
High Cost Medicine
Cancer Drugs Fund
Cancer Drugs Fund
NHSE
NHS England
Homecare
Homecare
CCG
CCG

Traffic Light Status Information

Status Description

Red SO

SPECIALIST ONLY - These drugs are deemed to be not appropriate for prescribing by GPs. Specialists should not ask GPs to prescribe these drugs.   

Green SI

SPECIALIST INITIATED - These drugs must be initiated, i.e. the first dose prescribed, by the specialist and then may be continued when appropriate by the patients GP following communication from the specialist.   

Green SA

SPECIALIST ADVISED Specialists may simply advise a patients GP to initiate these drugs themselves after they have made an initial assessment.   

Amber SC

SHARED CARE - Responsibility for prescribing may be transferred from secondary to primary care with the agreement of an individual GP and when agreed shared care arrangements have been established. The specialist MUST stabilize the patient before asking for care to be transferred. Only specialists should initiate these drugs. Prescribing should be transferred to GPs according to an Shared Care Agreement [SCA]   

netFormulary