, co-zidocapt 12.5/25 (hydrochlorothiazide

Tablets 2 , co-zidocapt 12.5/25 (hydrochlorothiazide

Combination products Products incorporating an

12.5 mg, captopril 25 mg), net price 28-tab pack = ACE inhibitor with a thiazide diuretic or a calcium-

channel blocker are available for the management of Brands include Capto-co hypertension. Use of these combination products should

Tablets , co-zidocapt 25/50 (hydrochlorothiazide

25 mg, captopril 50 mg), net price 28-tab pack = responded adequately to a single antihypertensive drug

be reserved for patients whose blood pressure has not

and who have been stabilised on the individual compo- Brands include Capto-co nents of the combination in the same proportions.

Capozide c (Squibb) A LS tablets , scored, co-zidocapt 12.5/25 (hydro-

chlorothiazide 12.5 mg, captopril 25 mg), net price 28- Indications mild to moderate essential hypertension

CAPTOPRIL

tab pack = £10.46 alone or with thiazide therapy and severe hyper-

Tablets , scored, co-zidocapt 25/50 (hydrochloro- tension resistant to other treatment; congestive heart

thiazide 25 mg, captopril 50 mg), net price 28-tab pack failure with left ventricular dysfunction (adjunct—see

= £7.45 (also available as Acezide c ) section 2.5.5); following myocardial infarction, see

dose; diabetic nephropathy (microalbuminuria greater than 30 mg/day) in type 1 diabetes

CILAZAPRIL

Contra-indications essential hypertension; congestive heart

Cautions see notes above

Indications

see notes above failure (adjunct—see section 2.5.5) Side-effects see notes above; tachycardia, serum

Cautions see notes above; severe hepatic impairment sickness, weight loss, stomatitis, maculopapular rash,

(Appendix 2)

photosensitivity, flushing and acidosis Contra-indications Dose

see notes above; ascites Side-effects see notes above; dyspnoea and bronch- . Hypertension, used alone, initially 12.5 mg twice

itis

daily; if used in addition to diuretic (see notes above),

Dose

or in elderly, initially 6.25 mg twice daily (first dose at bedtime); usual maintenance dose 25 mg twice daily;

. Hypertension, initially 1 mg once daily (reduced to max. 50 mg twice daily (rarely 3 times daily in severe

500 micrograms daily if used in addition to diuretic hypertension)

(see notes above), in the elderly, and in renal impair- ment), then adjusted according to response; usual

. Heart failure (adjunct), initially 6.25–12.5 mg 2–3 times daily under close medical supervision (see notes

maintenance dose 2.5–5 mg once daily; max. 5 mg above), increased gradually at intervals of at least 2

daily

weeks up to max. 150 mg daily in divided doses if . Heart failure (adjunct), initially 500 micrograms once tolerated

daily under close medical supervision (see notes . Prophylaxis after infarction in clinically stable patients

above), increased gradually to 1–2.5 mg once daily if with asymptomatic or symptomatic left ventricular

tolerated; max. 5 mg once daily dysfunction (radionuclide ventriculography or echo-

Vascace c (Roche) A cardiography undertaken before initiation), initially

Tablets , f/c, cilazapril 500 micrograms (white), net

6.25 mg, starting as early as 3 days after infarction, price 28-tab pack = £3.65; 1 mg (yellow), 28-tab pack then increased over several weeks to 150 mg daily (if

= £6.01; 2.5 mg (pink), 28-tab pack = £7.64; 5 mg tolerated) in divided doses

(brown), 28-tab pack = £13.28

BNF 57

2.5.5 Drugs affecting the renin-angiotensin system 103

40 mg (doses over 40 mg not shown to increase effi- Indications

ENALAPRIL MALEATE

cacy); if used in addition to diuretic see notes above hypertension; symptomatic heart failure

. Heart failure (adjunct), initially 10 mg once daily (adjunct—see section 2.5.5); prevention of sympto-

under close medical supervision (see notes above), matic heart failure in patients with asymptomatic left

increased gradually to 40 mg once daily if tolerated ventricular dysfunction Cautions see notes above; hepatic impairment

Fosinopril sodium (Non-proprietary) A (Appendix 2)

Tablets , fosinopril sodium 10 mg, net price 28-tab Contra-indications see notes above

pack = £2.48; 20 mg, 28-tab pack = £2.65 Side-effects see notes above; also dyspnoea; depres-

Staril c (Squibb) A

sion, asthenia; blurred vision; less commonly dry Tablets , fosinopril sodium 10 mg, net price 28-tab mouth, peptic ulcer, anorexia, ileus; arrhythmias,

pack = £11.20; 20 mg, 28-tab pack = £12.09 palpitation, flushing; confusion, nervousness, drowsi- ness, insomnia, vertigo; impotence; muscle cramps; tinnitus; alopecia, sweating; hyponatraemia; rarely

IMIDAPRIL HYDROCHLORIDE

stomatitis, glossitis, hepatic failure, Raynaud’s Indications essential hypertension syndrome, pulmonary infiltrates, allergic alveolitis,

Cautions see notes above; hepatic impairment dream abnormalities, gynaecomastia, Stevens-John-

(Appendix 2)

son syndrome, toxic epidermal necrolysis, exfoliative

dermatitis, pemphigus; very rarely gastro-intestinal see notes above angioedema Side-effects see notes above; dry mouth, glossitis,

Contra-indications

Dose ileus; bronchitis, dyspnoea; sleep disturbances, depression, confusion, blurred vision, tinnitus, impo-

. Hypertension, used alone, initially 5 mg once daily; if

tence

used in addition to diuretic (see notes above), or in

Dose

renal impairment, lower initial doses may be required; usual maintenance dose 20 mg once daily; max.

. Initially 5 mg daily before food; if used in addition to

40 mg once daily diuretic (see notes above), in elderly, in patients with heart failure, angina or cerebrovascular disease, or in

. Heart failure (adjunct), asymptomatic left ventricular renal or hepatic impairment, initially 2.5 mg daily; if dysfunction, initially 2.5 mg once daily under close

necessary increase dose at intervals of at least 3

ardiov

medical supervision (see notes above), increased weeks; usual maintenance dose 10 mg once daily; gradually over 2–4 weeks to 10–20 mg twice daily if

max. 20 mg daily (elderly, 10 mg daily) tolerated

ascular

Tanatril c (Trinity) A Enalapril Maleate (Non-proprietary) A Tablets , scored, imidapril hydrochloride 5 mg, net

Tablets , enalapril maleate 2.5 mg, net price 28-tab price 28-tab pack = £6.78; 10 mg, 28-tab pack = £7.66; pack = £1.31; 5 mg, 28-tab pack = £1.10; 10 mg, 28-tab

syst

20 mg, 28-tab pack = £9.20

pack = £1.12; 20 mg, 28-tab pack = £1.22 Brands include Ednyt

em

Innovace c (MSD) A LISINOPRIL

Tablets , enalapril maleate 2.5 mg, net price 28-tab Indications hypertension (but see notes above); pack = £5.35; 5 mg (scored), 28-tab pack = £7.51;

symptomatic heart failure (adjunct—see section

10 mg (red), 28-tab pack = £10.53; 20 mg (peach), 28- 2.5.5); short-term treatment following myocardial tab pack = £12.51

infarction in haemodynamically stable patients; renal complications of diabetes mellitus

With diuretic Cautions see notes above Note For mild to moderate hypertension in patients stabilised

on the individual components in the same proportions. For see notes above cautions, contra-indications, and side-effects of thiazides, see

Contra-indications

Side-effects see notes above; also less commonly section 2.2.1

tachycardia, palpitation, cerebrovascular accident, c (MSD)

Innozide myocardial infarction, Raynaud’s syndrome, confu- A Tablets sion, mood changes, vertigo, sleep disturbances, , yellow, scored, enalapril maleate 20 mg,

hydrochlorothiazide 12.5 mg, net price 28-tab pack = asthenia, impotence; rarely dry mouth, gynaecomas- £12.82

tia, alopecia, psoriasis; very rarely allergic alveolitis, Note Non-proprietary tablets containing enalapril maleate

pulmonary infiltrates, profuse sweating, pemphigus, (20 mg) and hydrochlorothiazide (12.5 mg) are available

Stevens-Johnson syndrome, and toxic epidermal necrolysis

Dose

. Hypertension, initially 10 mg once daily; if used in Indications hypertension; congestive heart failure

FOSINOPRIL SODIUM

addition to diuretic (see notes above) or in cardiac (adjunct—see section 2.5.5)

decompensation or in volume depletion, initially 2.5– Cautions

5 mg once daily; usual maintenance dose 20 mg once see notes above; hepatic impairment

daily; max. 80 mg once daily (Appendix 2)

Contra-indications . Heart failure (adjunct), initially 2.5 mg once daily

see notes above under close medical supervision (see notes above); Side-effects see notes above; chest pain; musculo-

increased in steps no greater than 10 mg at intervals skeletal pain

of at least 2 weeks up to max. 35 mg once daily if Dose

tolerated

. Hypertension, initially 10 mg daily, increased if . Prophylaxis after myocardial infarction, systolic blood necessary after 4 weeks; usual dose range 10–

pressure over 120 mmHg, 5 mg within 24 hours, fol-

2.5.5 Drugs affecting the renin-angiotensin system BNF 57 lowed by further 5 mg 24 hours later, then 10 mg after

mouth, photosensitivity, flushing, nervousness, mood

a further 24 hours, and continuing with 10 mg once changes, anxiety, drowsiness, sleep disturbance, tin- daily for 6 weeks (or continued if heart failure); sys-

nitus, influenza-like syndrome, sweating and dys- tolic blood pressure 100–120 mmHg, initially 2.5 mg

pnoea

once daily, increased to maintenance dose of 5 mg

Dose

once daily . Used alone, initially 7.5 mg once daily; if used in Note Should not be started after myocardial infarction if systolic blood pressure less than 100 mmHg; temporarily

addition to diuretic (see notes above), with nifedipine, reduce maintenance dose to 5 mg and if necessary 2.5 mg

in elderly, in renal or hepatic impairment, initially daily if systolic blood pressure 100 mmHg or less during

3.75 mg once daily; usual range 15–30 mg once daily; treatment; withdraw if prolonged hypotension occurs (sys-

doses above 30 mg daily not shown to increase effi- tolic blood pressure less than 90 mmHg for more than 1 hour)

cacy

. Renal complications of diabetes mellitus, initially 2.5– Perdix c (UCB Pharma) A

5 mg once daily adjusted according to response; usual Tablets , f/c, pink, scored, moexipril hydrochloride dose range 10–20 mg once daily

7.5 mg, net price 28-tab pack = £7.55; 15 mg, 28-tab Lisinopril (Non-proprietary)

A pack = £8.70

tem

Tablets, lisinopril (as dihydrate) 2.5 mg, net price 28-

sys

tab pack = 91p; 5 mg, 28-tab pack = £1.02; 10 mg, 28- tab pack = £1.10; 20 mg, 28-tab pack = £1.37

PERINDOPRIL ERBUMINE

Carace Indications c (Bristol-Myers Squibb) hypertension (but see notes above); A symptomatic heart failure (adjunct—see section

ascular

2.5.5); prophylaxis of cardiac events following myo- diov cardial infarction or revascularisation in stable cor- (orange), 28-tab pack = £11.89

Tablets , scored, lisinopril 5 mg, net price 28-tab pack = £8.51; 10 mg (yellow), 28-tab pack = £10.51; 20 mg

ar

onary artery disease

C Zestril c (AstraZeneca) A Cautions see notes above; hepatic impairment

2 Tablets , lisinopril (as dihydrate) 2.5 mg, net price 28-

(Appendix 2)

tab pack = £6.26; 5 mg (pink), 28-tab pack = £7.86; Contra-indications see notes above

10 mg (pink), 28-tab pack = £9.70; 20 mg (pink), 28- Side-effects see notes above; asthenia, mood and tab pack = £10.97

sleep disturbances With diuretic Dose

Note For mild to moderate hypertension in patients stabilised . Hypertension, initially 4 mg once daily in the morning on the individual components in the same proportions. For

for 1 month, subsequently adjusted according to cautions, contra-indications, and side-effects of thiazides, see

response; if used in addition to diuretic (see notes section 2.2.1

above), in elderly, in renal impairment, in cardiac Carace Plus c (Bristol-Myers Squibb) A decompensation, or in volume depletion, initially 2 mg

Carace 10 Plus tablets , blue, lisinopril 10 mg, once daily; max. 8 mg daily hydrochlorothiazide 12.5 mg, net price 28-tab pack =

. Heart failure (adjunct), initially 2 mg once daily in the £11.88

morning under close medical supervision (see notes Carace 20 Plus tablets , yellow, scored, lisinopril

above), increased after at least 2 weeks to max. 4 mg

20 mg, hydrochlorothiazide 12.5 mg, net price 28-tab once daily if tolerated pack = £13.44

. Following myocardial infarction or revascularisation, initially 4 mg once daily in the morning increased after Lisicostad c (Genus) A 2 weeks to 8 mg once daily if tolerated; ELDERLY

2 mg Lisicostad 10/12.5 mg tablets , scored, lisinopril (as

once daily for 1 week, then 4 mg once daily for 1 week, dihydrate) 10 mg, hydrochlorothiazide 12.5 mg, net

thereafter increased to 8 mg once daily if tolerated price 28-tab pack = £10.99 Lisicostad 20/12.5 mg tablets , scored, lisinopril (as

Perindopril (Non-proprietary) A dihydrate) 20 mg, hydrochlorothiazide 12.5 mg, net

Tablets , perindopril erbumine (= tert-butylamine) price 28-tab pack = £11.99

2 mg, net price 30-tab pack = £4.45; 4 mg, 30-tab pack = £4.21; 8 mg, 30-tab pack = £4.60. Label: 22 Zestoretic c (AstraZeneca) A Zestoretic 10 tablets , peach, lisinopril (as dihydrate)

Perindopril arginine

10 mg, hydrochlorothiazide 12.5 mg, net price 28-tab Coversyl c Arginine (Servier) A pack = £13.01

Tablets , f/c, perindopril arginine 2.5 mg (white), net Zestoretic 20 tablets , lisinopril (as dihydrate) 20 mg,

price 30-tab pack = £11.36; 5 mg (light green, scored), hydrochlorothiazide 12.5 mg, net price 28-tab pack =

30-tab pack = £11.36; 10 mg (green), 30-tab pack = £14.72

£11.36. Label: 22 Dose Hypertension, initially 5 mg once daily in the morning for 1 month, subsequently adjusted according to response; if used in

MOEXIPRIL HYDROCHLORIDE

addition to diuretic (see notes above), in elderly, in renal impair- ment, in cardiac decompensation, or in volume depletion, initially

Indications essential hypertension 2.5 mg once daily; max. 10 mg daily Cautions see notes above; hepatic impairment

Heart failure (adjunct), initially 2.5 mg once daily in the morning (Appendix 2) under close medical supervision (see notes above), increased after 2 weeks to max. 5 mg once daily if tolerated Contra-indications see notes above

Following myocardial infarction or revascularisation, initially 5 mg Side-effects see notes above; arrhythmias, angina,

once daily in the morning increased after 2 weeks to 10 mg once chest pain, syncope, cerebrovascular accident, myo-

daily if tolerated; ELDERLY 2.5 mg once daily for 1 week, then 5 mg cardial infarction; appetite and weight changes; dry once daily for 1 week, thereafter increased to 10 mg once daily if

tolerated

BNF 57

2.5.5 Drugs affecting the renin-angiotensin system 105

Perindopril arginine with diuretic cholysis, confusion, nervousness, depression, anxiety, Note For hypertension not adequately controlled by perindo-

impotence, decreased libido, alopecia, bronchitis and pril alone. For cautions, contra-indications, and side-effects of indapamide, see section 2.2.1

muscle cramps Dose Coversyl c Arginine Plus (Servier) A . Hypertension, initially 1.25 mg once daily, increased

Tablets , f/c, perindopril arginine 5 mg, indapamide at intervals of 1–2 weeks; usual range 2.5–5 mg once

1.25 mg, net price 30-tab pack = £14.49. Label: 22 daily; max. 10 mg once daily; if used in addition to diuretic see notes above

. Heart failure (adjunct), initially 1.25 mg once daily Indications

QUINAPRIL

under close medical supervision (see notes above), essential hypertension; congestive heart

increased gradually at intervals of 1–2 weeks to max. failure (adjunct—see section 2.5.5)

10 mg daily if tolerated (daily doses of 2.5 mg or more Cautions see notes above; hepatic impairment

may be taken in 1–2 divided doses) (Appendix 2)

. Prophylaxis after myocardial infarction (started in Contra-indications see notes above

hospital 3 to 10 days after infarction), initially 2.5 mg Side-effects see notes above; asthenia, chest pain,

twice daily, increased after 2 days to 5 mg twice daily; oedema, flatulence, nervousness, depression, insom-

maintenance 2.5–5 mg twice daily nia, blurred vision, impotence, and back pain

Note If initial 2.5-mg dose not tolerated, give 1.25 mg twice Dose

daily for 2 days before increasing to 2.5 mg twice daily, then

5 mg twice daily

. Hypertension, initially 10 mg once daily; with a diuretic (see notes above), in elderly, or in renal

. Prophylaxis of cardiovascular events or stroke, initi- ally 2.5 mg once daily, increased after 1 week to 5 mg impairment initially 2.5 mg daily; usual maintenance

once daily, then increased after a further 3 weeks to dose 20–40 mg daily in single or 2 divided doses; up to

10 mg once daily

80 mg daily has been given . Heart failure (adjunct), initial dose 2.5 mg daily under

Ramipril (Non-proprietary) A close medical supervision (see notes above),

Capsules , ramipril 1.25 mg, net price 28-cap pack = increased gradually to 10–20 mg daily in 1–2 divided

£1.07; 2.5 mg, 28-cap pack = £1.15; 5 mg, 28-cap pack

doses if tolerated; max. 40 mg daily = £1.29; 10 mg, 28-cap pack = £1.54 Brands include Lopace

ardiov C

Quinapril (Non-proprietary) A Tablets , quinapril (as hydrochloride) 5 mg, net price

Tablets , ramipril 1.25 mg, net price 28-tab pack = 28-tab pack = £1.78; 10 mg, 28-tab pack = £2.16;

£1.42; 2.5 mg, 28-tab pack = £1.58; 5 mg, 28-tab pack

ascular

20 mg, 28-tab pack = £2.56; 40 mg, 28-tab pack = = £1.93; 10 mg, 28-tab pack = £2.44 £3.26

Tritace c (Aventis Pharma) Brands include Quinil

A Tablets , scored, ramipril 1.25 mg (white), net price 28-

syst

Accupro c (Pfizer) A tab pack = £5.30; 2.5 mg (yellow), 28-tab pack = £7.51; Tablets , f/c, quinapril (as hydrochloride) 5 mg

5 mg (red), 28-tab pack = £10.46; 10 mg (white), 28-

em

(brown), net price 28-tab pack = £8.60; 10 mg (brown),

tab pack = £14.24

28-tab pack = £8.60; 20 mg (brown), 28-tab pack = Titration pack, tablets , 35-day starter pack of rami- £10.79; 40 mg (red-brown), 28-tab pack = £9.75

price = £13.00

With diuretic Note For hypertension in patients stabilised on the individual

With calcium-channel blocker components in the same proportions. For cautions, contra- indications, and side-effects of thiazides, see section 2.2.1

Note For hypertension in patients stabilised on the individual components in the same proportions. For cautions, contra- Accuretic c (Pfizer) A indications, and side-effects of felodipine, see section 2.6.2

Tablets , pink, f/c, scored, quinapril (as hydrochloride) Triapin c c (Aventis Pharma) TA

10 mg, hydrochlorothiazide 12.5 mg, net price 28-tab Triapin tablets , f/c, brown, ramipril 5 mg, felodipine pack = £11.75

5 mg (m/r), net price 28-tab pack = £32.26. Label: 25 Triapin mite c tablets , f/c, orange, ramipril 2.5 mg,

felodipine 2.5 mg (m/r), net price 28-tab pack = Indications mild to moderate hypertension; conges-

RAMIPRIL

£25.55. Label: 25

tive heart failure (adjunct—see section 2.5.5); follow- ing myocardial infarction in patients with clinical evidence of heart failure; susceptible patients over 55

TRANDOLAPRIL

years, prevention of myocardial infarction, stroke, Indications mild to moderate hypertension; following cardiovascular death or need of revascularisation

myocardial infarction in patients with left ventricular procedures (consult product literature)

dysfunction

Cautions see notes above; hepatic impairment Cautions see notes above; hepatic impairment (Appendix 2)

(Appendix 2)

Contra-indications see notes above Contra-indications see notes above Side-effects see notes above; arrhythmias, angina,

Side-effects see notes above; also ileus, dry mouth; chest pain, syncope, cerebrovascular accident, myo-

tachycardia, palpitation, arrhythmias, angina, transi- cardial infarction, loss of appetite, stomatitis, dry

ent ischaemic attacks, cerebral haemorrhage, myo- mouth, skin reactions including erythema multiforme

cardial infarction, syncope; dyspnoea, bronchitis; and pemphigoid exanthema; precipitation or exacer-

asthenia, nervousness, sleep disturbances; hot bation of Raynaud’s syndrome; conjunctivitis, ony-

flushes; alopecia, sweating, skin reactions including

2.5.5 Drugs affecting the renin-angiotensin system BNF 57 Stevens-Johnson syndrome, toxic epidermal necro-

trophy), may not benefit from an angiotensin-II receptor lysis, and psoriasis-like efflorescence

antagonist. Interactions: Appendix 1 (angiotensin-II Dose

receptor antagonists). . Hypertension, initially 500 micrograms once daily,

increased at intervals of 2–4 weeks; usual range 1– Contra-indications Angiotensin-II receptor antago-

2 mg once daily; max. 4 mg daily; if used in addition to nists, like the ACE inhibitors, should also be avoided in diuretic see notes above

pregnancy (Appendix 4) and breast-feeding (Appendix . Prophylaxis after myocardial infarction (starting as

early as 3 days after infarction), initially 500 micr- ograms once daily, gradually increased to max. 4 mg

Side-effects Side-effects are usually mild. Sympto- once daily

matic hypotension including dizziness may occur, parti- Note If symptomatic hypotension develops during titration,

cularly in patients with intravascular volume depletion do not increase dose further; if possible, reduce dose of any adjunctive treatment and if this is not effective or feasible,

(e.g. those taking high-dose diuretics). Hyperkalaemia reduce dose of trandolapril

occurs occasionally; angioedema has also been reported with some angiotensin-II receptor antagonists.

Trandolapril (Non-proprietary) A

tem

Capsules , trandolapril 500 micrograms, net price 14-

sys

cap pack = £1.41; 1 mg, 28-cap pack = £6.86; 2 mg, 28-

CANDESARTAN CILEXETIL

cap pack = £6.86; 4 mg, 28-cap pack = £11.61

Indications

c Gopten hypertension; heart failure with impaired (Abbott) A left ventricular systolic function in conjunction with

ascular

Capsules , trandolapril 500 micrograms (red/yellow), an ACE inhibitor, or when ACE inhibitors are not net price 14-cap pack = £1.40; 1 mg (red/orange), 28-

tolerated (see also section 2.5.5)

diov

cap pack = £12.28; 2 mg (red/red), 28-cap pack = Cautions see notes above; hepatic impairment

C ar

£6.86; 4 mg (red/maroon), 28-cap pack = £11.64 (Appendix 2); renal impairment (Appendix 3) Contra-indications see notes above; also cholestasis

Note Side-effects see notes above; also vertigo, headache; For hypertension in patients stabilised on the individual components in the same proportions. For cautions, contra-

2 With calcium-channel blocker

very rarely nausea, hepatitis, blood disorders, hypo- indications, and side-effects of verapamil, see section 2.6.2

natraemia, back pain, arthralgia, myalgia, rash, urti- Tarka c

caria, pruritus

(Abbott) TAU Capsules Dose , pink, trandolapril 2 mg, verapamil hydro- chloride 180 mg (m/r), net price 28 cap-pack =

. Hypertension, initially 8 mg (hepatic impairment £17.85. Label: 25

2 mg, renal impairment or intravascular volume depletion 4 mg) once daily, increased if necessary at intervals of 4 weeks to max. 32 mg once daily; usual maintenance dose 8 mg once daily

. Heart failure, initially 4 mg once daily, increased at intervals of at least 2 weeks to ‘target’ dose of 32 mg

2.5.5.2 Angiotensin-II receptor

once daily or to max. tolerated dose

Amias c (Takeda) A Tablets , candesartan cilexetil 2 mg (white), net price Candesartan, eprosartan, irbesartan, losartan, olme-

antagonists

7-tab pack = £2.99; 4 mg (white, scored), 7-tab pack = sartan, telmisartan, and valsartan are angiotensin-II

£3.24, 28-tab pack = £8.15; 8 mg (pink, scored), 28-tab receptor antagonists with many properties similar to

pack = £9.89; 16 mg (pink, scored), 28-tab pack = those of the ACE inhibitors. However, unlike ACE inhi-

£12.72; 32 mg (pink, scored), 28-tab pack = £16.13 bitors, they do not inhibit the breakdown of bradykinin

and other kinins, and thus are unlikely to cause the persistent dry cough which commonly complicates ACE

EPROSARTAN

for patients who have to discontinue an ACE inhibitor hypertension (see also notes above) because of persistent cough. Cautions see notes above; also hepatic impairment

inhibitor therapy. They are therefore a useful alternative

Indications

(Appendix 2); renal impairment (Appendix 3) An angiotensin-II receptor antagonist may be used as an

Contra-indications see notes above alternative to an ACE inhibitor in the management of

Side-effects see notes above; also flatulence, hyper- heart failure (section 2.5.5) or diabetic nephropathy

triglyceridaemia, arthralgia, rhinitis; rarely headache, (section 6.1.5).

asthenia, anaemia, hypersensitivity reactions (includ- ing rash, pruritus, urticaria); very rarely nausea

Cautions Angiotensin-II receptor antagonists should Dose

. 600 mg once daily (elderly over 75 years, mild to Monitoring of plasma-potassium concentration is

be used with caution in renal artery stenosis (see also Renal Effects under ACE Inhibitors, section 2.5.5.1).

moderate hepatic impairment, renal impairment, advised, particularly in the elderly and in patients with

initially 300 mg once daily); if necessary increased renal impairment; lower initial doses may be appropri-

after 2–3 weeks to 800 mg once daily ate in these patients. Angiotensin-II receptor antago-

Teveten c (Solvay) A nists should be used with caution in aortic or mitral

Tablets , f/c, eprosartan (as mesilate) 300 mg (white), valve stenosis and in hypertrophic cardiomyopathy.

net price 28-tab pack = £11.63; 400 mg (pink), 56-tab Those with primary aldosteronism, and Afro-Caribbean

pack = £15.77; 600 mg (white), 28-tab pack = £14.31. patients (particularly those with left ventricular hyper-

Label: 21

BNF 57

2.5.5 Drugs affecting the renin-angiotensin system 107

IRBESARTAN

With diuretic

Indications Note For hypertension not adequately controlled with losartan

hypertension; renal disease in hyperten- alone. For cautions, contra-indications, and side-effects of thi- sive type 2 diabetes mellitus (see also notes above)

azides, see section 2.2.1

Cautions see notes above Cozaar-Comp c (MSD) A Contra-indications see notes above

Tablets 50/12.5 , yellow, f/c, losartan potassium Side-effects see notes above; also nausea, vomiting;

50 mg, hydrochlorothiazide 12.5 mg, net price 28-tab fatigue; musculoskeletal pain; less commonly diarr-

pack = £12.80

hoea, dyspepsia, flushing, tachycardia, chest pain, Tablets 100/12.5 , white, f/c, losartan potassium cough, and sexual dysfunction; rarely rash, urticaria;

100 mg, hydrochlorothiazide 12.5 mg, net price 28-tab very rarely headache, myalgia, arthralgia, tinnitus,

pack = £16.18

Tablets 100/25 , yellow, f/c, losartan potassium Dose

taste disturbance, hepatitis, renal dysfunction, and cutaneous vasculitis

100 mg, hydrochlorothiazide 25 mg, net price 28-tab pack = £16.18

. Hypertension, initially 150 mg once daily, increased if necessary to 300 mg once daily (in haemodialysis or in ELDERLY over 75 years, initial dose of 75 mg once daily may be used); CHILD not recommended

OLMESARTAN MEDOXOMIL

. Renal disease in hypertensive type 2 diabetes mellitus, Indications hypertension (see also notes above) initially 150 mg once daily, increased to 300 mg once

Cautions see notes above; hepatic impairment (avoid daily if tolerated (in haemodialysis or in ELDERLY over

in severe impairment; Appendix 2); renal impairment

75 years, consider initial dose of 75 mg once daily); (avoid if creatinine clearance less than 20 mL/minute; CHILD not recommended

Appendix 3) Aprovel c (Bristol-Myers Squibb, Sanofi-Synthelabo) A Contra-indications see notes above; biliary obstruc- Tablets , f/c, irbesartan 75 mg, net price 28-tab pack =

tion

£10.29; 150 mg, 28-tab pack = £12.57; 300 mg, 28-tab Side-effects see notes above; also gastro-intestinal

pack = £16.91 disturbances; chest pain, peripheral oedema, hyper- triglyceridaemia; fatigue; influenza-like symptoms,

ardiov

With diuretic Note For hypertension not adequately controlled with irbesar-

cough, pharyngitis, rhinitis; urinary-tract infection;

haematuria, hyperuricaemia; arthritis, musculo- tan alone. For cautions, contra-indications, and side-effects of

skeletal pain; less commonly angina, vertigo, rash; very

ascular

thiazides, see section 2.2.1 rarely headache, thrombocytopenia, myalgia, pruritus, CoAprovel c (Bristol-Myers Squibb, Sanofi-Synthelabo)

urticaria

A Dose

syst

Tablets , f/c, irbesartan 150 mg, hydrochlorothiazide . Initially 10 mg once daily; if necessary increased to

12.5 mg (peach), net price 28-tab pack = £12.57;

20 mg once daily; max. 40 mg daily

em

irbesartan 300 mg, hydrochlorothiazide 12.5 mg (peach), 28-tab pack = £16.91; irbesartan 300 mg,

Olmetec c (Sankyo) A hydrochlorothiazide 25 mg (pink), 28-tab pack =

Tablets , f/c, olmesartan medoxomil 10 mg, net price £16.91

28-tab pack = £10.95; 20 mg, 28-tab pack = £12.95;

40 mg, 28-tab pack = £17.50

LOSARTAN POTASSIUM

With diuretic

Indications hypertension (including reduction of Note For hypertension not adequately controlled with olme- stroke risk in hypertension with left ventricular

sartan alone. For cautions, contra-indications, and side-effects hypertrophy); diabetic nephropathy in type 2 diabetes

of thiazides, see section 2.2.1 mellitus (see also notes above)

Olmetec Plus c (Sankyo) TA Cautions see notes above; hepatic impairment

Tablets , f/c, olmesartan medoxomil 20 mg, hydro- (Appendix 2); renal impairment (Appendix 3)

chlorothiazide 12.5 mg (red-yellow), net price 28-tab Contra-indications see notes above

pack = £12.95; olmesartan medoxomil 20 mg, hydro- Side-effects

chlorothiazide 25 mg (pink), 28-tab pack = £12.95 see notes above; diarrhoea, cough, arthralgia, myalgia, asthenia, fatigue, migraine,

vertigo, urticaria, pruritus, rash; rarely hepatitis, anaemia (in severe renal disease or following renal

TELMISARTAN

transplantation), thrombocytopenia, vasculitis (including Henoch-Scho¨nlein purpura), and anaphy-

Indications hypertension (see also notes above) laxis

Cautions see notes above; hepatic impairment Dose

(Appendix 2; avoid in severe impairment); renal Usually 50 mg once daily (intravascular volume

impairment (Appendix 3) . depletion, initially 25 mg once daily); if necessary

Contra-indications see notes above; biliary obstruc- increased after several weeks to 100 mg once daily;

tion

ELDERLY over 75 years initially 25 mg daily Side-effects see notes above; also gastro-intestinal Cozaar c

disturbances; chest pain; influenza-like symptoms (MSD) A including pharyngitis and sinusitis; urinary-tract

Tablets , f/c, losartan potassium 25 mg, net price 28- infection; arthralgia, myalgia, back pain, leg cramps; tab pack = £16.18; 50 mg (scored), 28-tab pack =

eczema; less commonly dry mouth, flatulence, anxiety, £12.80; 100 mg, 28-tab pack = £16.18

vertigo, tendinitis-like symptoms, abnormal vision,

BNF 57 increased sweating; rarely bradycardia, tachycardia,

2.6 Nitrates, calcium-channel blockers, and other antianginal drugs

With diuretic

dyspnoea, insomnia, depression, blood disorders, Note For hypertension not adequately controlled by valsartan increase in uric acid, eosinophilia, rash, and pruritus;

alone. For cautions, contra-indications, and side-effects of thi- syncope and asthenia also reported

azides, see section 2.2.1 Dose

Co-Diovan c (Novartis) TA . Usually 40 mg once daily (but 20 mg may be suffi-

Tablets 80/12.5 , orange, f/c, valsartan 80 mg, cient), increased if necessary after at least 4 weeks, to

hydrochlorothiazide 12.5 mg, net price 28-tab pack = max. 80 mg once daily

Tablets 160/12.5 , red, f/c, valsartan 160 mg, (Boehringer Ingelheim) A hydrochlorothiazide 12.5 mg, net price 28-tab pack =

Micardis c

Tablets , telmisartan 20 mg, net price 28-tab pack =

£9.25; 40 mg, 28-tab pack = £11.34; 80 mg, 28-tab Tablets 160/25 , brown-orange, f/c, valsartan pack = £14.18

160 mg, hydrochlorothiazide 25 mg, net price 28-tab pack = £21.66

With diuretic tem Note For patients with hypertension not adequately controlled by telmisartan alone. For cautions, contra-indications, and side-

2.5.5.3 Renin inhibitors

sys effects of thiazides, see section 2.2.1 Renin inhibitors inhibit renin directly; renin converts

Micardis Plus c (Boehringer Ingelheim) A angiotensinogen to angiotensin I. Aliskiren is licensed Tablets 40/12.5 , red/white, telmisartan 40 mg,

ascular for the treatment of hypertension, either alone or in

hydrochlorothiazide 12.5 mg, net price 28-tab pack = combination with other antihypertensives.

diov

£11.34 The Scottish Medicines Consortium (p. 3) has advised ar C Tablets 80/12.5 , red/white, telmisartan 80 mg,

(December 2008) that aliskiren (Rasilez c ) is not hydrochlorothiazide 12.5 mg, net price 28-tab pack =

recommended for use within NHS Scotland for the

treatment of essential hypertension. Tablets 80/25 , yellow/white, telmisartan 80 mg,

hydrochlorothiazide 25 mg, net price 28-tab pack = £14.18

ALISKIREN

Indications essential hypertension Cautions patients taking concomitant diuretics, on a

low-sodium diet, or who are dehydrated (first doses may cause hypotension—initiate with care); renal

artery stenosis; renal impairment (Appendix 3); Indications

VALSARTAN

monitor plasma-potassium concentration and renal hypertension; myocardial infarction with

function in renal impairment, diabetes mellitus, and left ventricular failure or left ventricular systolic dys-

heart failure; interactions: Appendix 1 (aliskiren) function (adjunct—see section 2.5.5 and section

pregnancy (Appendix 4); breast- Cautions

Contra-indications 2.10.1)

feeding (Appendix 5) see notes above; hepatic impairment

(Appendix 2); renal impairment (Appendix 3) diarrhoea; less commonly rash; rarely Contra-indications

Side-effects

angioedema; anaemia and hyperkalaemia also see notes above, cirrhosis, biliary

Side-effects see notes above; rarely anaemia, neutro- . ADULT over 18 years, 150 mg once daily, increased if penia; very rarely diarrhoea, taste disturbance, syn-

necessary to 300 mg once daily cope, fatigue, cough, headache, thrombocytopenia, Rasilez epistaxis, arthralgia, myalgia, and hypersensitivity c (Novartis) TA

reactions (including rash, pruritus, vasculitis, and Tablets , f/c, aliskiren (as hemifumarate) 150 mg serum sickness)

(pink), net price 28-tab pack = £19.80; 300 mg (red), Dose

net price 28-tab pack = £23.80. Label: 21 . Hypertension, usually 80 mg once daily (initially

40 mg once daily in intravascular volume depletion); if necessary increased at intervals of 4 weeks up to max. 320 mg daily; ELDERLY over 75 years, initially 40 mg

Nitrates, calcium-channel

once daily

blockers, and other

. Myocardial infarction, initially 20 mg twice daily

increased over several weeks to 160 mg twice daily if

antianginal drugs

tolerated

c 2.6.1 Diovan Nitrates (Novartis) A Capsules , valsartan 40 mg (grey), net price 28-cap

2.6.2 Calcium-channel blockers

pack = £16.44; 80 mg (grey/pink), 28-cap pack =

2.6.3 Other antianginal drugs

£16.44, 98-cap pack = £57.54; 160 mg (dark grey/

2.6.4 Peripheral vasodilators and related

pink), 28-cap pack = £21.66, 98-cap pack = £75.81

drugs

Tablets , f/c, valsartan 40 mg (yellow, scored), net price 7-tab pack = £4.11; 320 mg (dark grey-violet),

Nitrates, calcium-channel blockers, and potassium- 28-tab pack = £23.80, 98-tab pack = £83.30

channel activators have vasodilating effects. Vaso-

BNF 57

2.6.1 Nitrates 109

dilators can act in heart failure by arteriolar dilatation oedema, or continuing myocardial ischaemia; hyperoxia which reduces both peripheral vascular resistance and

should be avoided and particular care is required in left ventricular pressure during systole resulting in

patients with chronic obstructive airways disease. improved cardiac output. They can also cause venous dilatation which results in dilatation of capacitance

Nitrates (section 2.6.1) are used to relieve ischaemic vessels, increase of venous pooling, and diminution of

pain. If sublingual glyceryl trinitrate is not effective, venous return to the heart (decreasing left ventricular

intravenous or buccal glyceryl trinitrate or intravenous end-diastolic pressure).

isosorbide dinitrate is given. If pain continues, diamor- phine (section 4.7.2) can be given by slow intravenous injection; an antiemetic such as metoclopramide should also be given (section 4.6).

Angina

Aspirin (chewed or dispersed in water) is given for its It is important to distinguish unstable angina from stable

antiplatelet effect in a dose of 300 mg (section 2.9). If angina. Stable angina usually results from atherosclero-

aspirin is given before arrival at hospital, a note saying tic plaques in the coronary arteries and is often pre-

that it has been given should be sent with the patient. cipitated by exertion and relieved by rest. Unstable

Clopidogrel in a dose of 300 mg (section 2.9) and a low angina is usually due to plaque rupture and is often

molecular weight heparin or fondaparinux (section characterised by new onset severe angina or sudden

2.8.1), should also be given. worsening of previously stable angina. Treatment of stable and unstable angina involves management of

Patients without contra-indications should receive beta- acute anginal pain, and long-term management to pre-

blockers (section 2.4) which should be continued inde- vent angina attacks and to reduce the risk of cardiovas-

finitely. In patients without left ventricular dysfunction cular events.

and in whom beta-blockers are inappropriate, diltiazem or verapamil can be given (section 2.6.2).

Stable angina Acute attacks of stable angina should The glycoprotein IIb/IIIa inhibitors eptifibatide and

be managed with sublingual glyceryl trinitrate; sublin- tirofiban (section 2.9) are recommended (with aspirin gual glyceryl trinitrate can also be taken before perform-

and heparin) for unstable angina or for non-ST-segment ing activities that are known to bring on an attack. If

elevation myocardial infarction in patients at a high risk

attacks occur more than twice a week, regular drug of either myocardial infarction or death. therapy is required and should be introduced in a step-

Abciximab, eptifibatide, or tirofiban can also be used

ardiov

wise manner according to response. with aspirin and heparin in patients undergoing percu- Patients with mild or moderate stable angina should be

taneous coronary intervention, to reduce the immediate

ascular

given a beta-blocker (section 2.4). In those with left- risk of vascular occlusion. ventricular dysfunction, beta-blocker treatment should

Revascularisation procedures are often appropriate for

be started at a very low dose and titrated very slowly patients with unstable angina. over a period of weeks or months (section 2.5.5).

syst

Long-term management The need for long-term For those patients in whom beta-blockers are not toler-

angina treatment or for coronary angiography should

em

ated or are contra-indicated, a long-acting nitrate (sec-

be assessed. Most patients will require standard angina tion 2.6.1) or a rate-limiting calcium-channel blocker

treatment (see Stable angina) to prevent recurrence of (diltiazem or verapamil, section 2.6.2) can be used; in

symptoms.

patients with left-ventricular dysfunction, diltiazem and verapamil are contra-indicated because heart failure may be precipitated (important: see p. 113); however,

a long-acting dihydropyridine calcium-channel blocker, Prevention of cardiovascular events Patients with such as amlodipine or felodipine, is suitable. Nicorandil

stable and unstable angina should be given advice and or ivabradine (section 2.6.3) are alternatives.

treatments to reduce their cardiovascular risk. The importance of life-style changes, especially stopping

When a single drug fails to control symptoms, combina- smoking, should be emphasised. Patients should take tion treatment can be used. A calcium-channel blocker

aspirin indefinitely in a dose of 75 mg daily. A combina- can be added to a beta-blocker, although combining

tion of aspirin and clopidogrel is given for up to 12 verapamil with a beta-blocker should be avoided (see

months in patients with non-ST-segment elevation p. 118); combinations including diltiazem and a beta-

acute coronary syndromes (section 2.9). An ACE inhi- blocker should be used with caution. Long-acting

bitor (section 2.5.5.1) and a statin (section 2.12) should nitrates can also be used with a beta-blocker or a cal-

also be given.

cium-channel blocker, if appropriate. Combinations that include nicorandil can also be considered.

Patients should be referred to a specialist if a combina- tion of two drugs fails to control symptoms. Revascular-

2.6.1 Nitrates

isation procedures may be appropriate. Nitrates have a useful role in angina (for details on the Unstable angina Unstable angina and non-ST-seg- management of stable angina, see section 2.6). Although ment elevation myocardial infarction are managed simi-

they are potent coronary vasodilators, their principal larly. The aims of management are to provide suppor-

benefit follows from a reduction in venous return which tive care and pain relief during the acute attack and to

reduces left ventricular work. Unwanted effects such as prevent further cardiac events and death. For advice on

flushing, headache, and postural hypotension may limit the management of patients with ST-segment elevation

therapy, especially when angina is severe or when acute myocardial infarction, see section 2.10.1.

patients are unusually sensitive to the effects of nitrates. Initial management Oxygen (section 3.6) should be

Sublingual glyceryl trinitrate is one of the most effec- administered if there is evidence of hypoxia, pulmonary

tive drugs for providing rapid symptomatic relief of

2.6.1 Nitrates BNF 57 angina, but its effect lasts only for 20 to 30 minutes; the

heartburn; flushing; temporary hypoxaemia; rash; 300-microgram tablet is often appropriate when glycer-

application site reactions with transdermal patches; yl trinitrate is first used. The aerosol spray provides an

very rarely angle-closure glaucoma alternative method of rapid relief of symptoms for those

Injection Specific side-effects following injection (particu- who find difficulty in dissolving sublingual preparations.

larly if given too rapidly) include severe hypotension, dia- Duration of action may be prolonged by modified-release

phoresis, apprehension, restlessness, muscle twitching, ret- and transdermal preparations (but tolerance may devel-

rosternal discomfort, palpitation, abdominal pain, syncope; prolonged administration has been associated with

op, see below). methaemoglobinaemia Isosorbide dinitrate is active sublingually and is a more

Dose

stable preparation for those who only require nitrates . Sublingually , 0.3–1 mg, repeated as required infrequently. It is also effective by mouth for prophy-

. By intravenous infusion , 10–200 micrograms/min- laxis; although the effect is slower in onset, it may

ute

persist for several hours. Duration of action of up to . By transdermal application , see under preparations

12 hours is claimed for modified-release preparations. The activity of isosorbide dinitrate may depend on the

Short-acting tablets and sprays production of active metabolites, the most important of

Glyceryl Trinitrate (Non-proprietary) tem which is isosorbide mononitrate. Isosorbide mono-

Sublingual tablets , glyceryl trinitrate 300 micr- sys nitrate itself is also licensed for angina prophylaxis;

ograms, net price 100 = £2.71; 500 micrograms, 100 = modified-release formulations (for once daily adminis-

£2.84; 600 micrograms, 100 = £13.77. Label: 16 tration) are available.

Note Glyceryl trinitrate tablets should be supplied in glass con- Glyceryl trinitrate or isosorbide dinitrate may be tried by

tainers of not more than 100 tablets, closed with a foil-lined cap,

ascular intravenous injection when the sublingual form is ineffec-

and containing no cotton wool wadding; they should be discarded after 8 weeks in use

diov tive in patients with chest pain due to myocardial infarction or severe ischaemia. Intravenous injections Aerosol spray , glyceryl trinitrate 400 micrograms/

C ar are also useful in the treatment of acute left ventricular metered dose, net price 200-dose unit = £3.13 Dose treatment or prophylaxis of angina, spray 1–2 doses under

2 failure.

tongue and then close mouth