Lipid-regulating drugs 141

2.12 Lipid-regulating drugs 141

C ardiov

ascular

syst em

2.12 Lipid-regulating drugs BNF 57 progression of coronary atherosclerosis in primary

tab pack = £2.77. Counselling, muscle effects, see hypercholesterolaemia and concomitant coronary

notes above

heart disease; prevention of coronary events after percutaneous coronary intervention

Lipostat c (Squibb) A Cautions see notes above

Tablets , all yellow, pravastatin sodium 10 mg, net Contra-indications see notes above

price 28-tab pack = £15.05; 20 mg, 28-tab pack = Side-effects

£27.61; 40 mg, 28-tab pack = £27.61. Counselling, see notes above; also very rarely vasculi-

muscle effects, see notes above tis

Dose . Hypercholesterolaemia or combined hyperlipidaemia,

initially 20–40 mg daily in the evening, adjusted at

ROSUVASTATIN

intervals of at least 4 weeks; up to 80 mg daily may be Indications primary hypercholesterolaemia (type IIa required; CHILD under 18 years, not recommended

including heterozygous familial hypercholesterol- . Prevention of progression of coronary atherosclerosis,

aemia), mixed dyslipidaemia (type IIb), or homozy-

40 mg daily in the evening gous familial hypercholesterolaemia in patients who tem . Following percutaneous coronary intervention, 80 mg

have not responded adequately to diet and other daily

appropriate measures

sys

Cautions Lescol see notes above; patients of Asian origin (see c (Novartis) A , fluvastatin (as sodium salt) 20 mg (brown/

Capsules under Dose); max. dose 20 mg in patients with risk yellow), net price 28-cap pack = £15.26; 40 mg

factors for myopathy or rhabdomyolysis (including

ascular

(brown/orange), 28-cap pack = £15.26, 56-cap pack = personal or family history of muscular disorders or £30.53. Counselling, muscle effects, see notes above

toxicity); renal impairment (avoid if creatinine clear-

diov

ance less than 30 mL/minute; Appendix 3) ar C Contra-indications

Modified release see notes above c (Novartis)

Lescol Side-effects XL A 2 see notes above; also proteinuria; very

Tablets , m/r, yellow, fluvastatin (as sodium salt) rarely haematuria

80 mg, net price 28-tab pack = £19.20. Label: 25,

Dose

counselling, muscle effects, see notes above . Initially 5–10 mg once daily increased if necessary at Dose

80 mg once daily (dose form not appropriate for initial dose intervals of at least 4 weeks to 20 mg once daily, titration in hypercholesterolaemia or combined hyperlipidaemia)

increased after further 4 weeks to 40 mg daily only in severe hypercholesterolaemia with high cardiovascu- lar risk and under specialist supervision; ELDERLY

initially 5 mg once daily; patient of ASIAN origin, initi- Indications

PRAVASTATIN SODIUM

ally 5 mg once daily increased if necessary to max. adjunct to diet for primary hyper-

20 mg daily

cholesterolaemia or combined (mixed) hyperlipidae- Note Initially 5 mg once daily with concomitant fibrate mias in patients who have not responded adequately

increased if necessary to max. 20 mg daily to dietary control; adjunct to diet to prevent cardio-

Crestor vascular events in patients with hypercholesterol- c (AstraZeneca) A aemia; prevention of cardiovascular events in patients

Tablets , f/c, rosuvastatin (as calcium salt) 5 mg (yel- with previous myocardial infarction or unstable

low), net price 28-tab pack = £18.03; 10 mg (pink), 28- angina; reduction of hyperlipidaemia in patients

tab pack = £18.03; 20 mg (pink), 28-tab pack = £26.02; receiving immunosuppressive therapy following solid-

40 mg (pink), 28-tab pack = £29.69. Counselling, organ transplantation

muscle effects, see notes above Cautions see notes above; renal impairment (Appen- dix 3) Contra-indications see notes above

SIMVASTATIN

Side-effects see notes above; less commonly abnormal urination (including dysuria, nocturia and frequency); Indications primary hypercholesterolaemia, homozy- very rarely fulminant hepatic necrosis

gous familial hypercholesterolaemia or combined Dose

(mixed) hyperlipidaemia in patients who have not responded adequately to diet and other appropriate

. Hypercholesterolaemia or combined hyperlipidae- measures; prevention of cardiovascular events in mias, 10–40 mg once daily at night, adjusted at inter-

patients with atherosclerotic cardiovascular disease or vals of at least 4 weeks

diabetes mellitus . Familial hypercholesterolaemia, CHILD 8–14 years 10–

Cautions see notes above; renal impairment (Appen-

20 mg once daily at night, 14–18 years 10–40 mg once

dix 3)

daily at night Contra-indications see notes above . Prevention of cardiovascular events, 40 mg once daily

at night Side-effects see notes above; also rarely anaemia . Dose Post-transplantation hyperlipidaemia, initially 20 mg

once daily at night, increased if necessary (under . Primary hypercholesterolaemia, combined hyper- close medical supervision) to max. 40 mg once daily

lipidaemia, 10–20 mg daily at night, adjusted at at night

intervals of at least 4 weeks; usual range 10–80 mg once daily at night

Pravastatin (Non-proprietary) A . Homozygous familial hypercholesterolaemia, 40 mg Tablets , pravastatin sodium 10 mg, net price 28-tab

daily at night or 80 mg daily in 3 divided doses (with pack = £1.73; 20 mg, 28-tab pack = £2.22; 40 mg, 28-

largest dose at night)

BNF 57

2.12 Lipid-regulating drugs 143

. Prevention of cardiovascular events, initially 20– Constipation is common, but diarrhoea has occurred,

40 mg once daily at night, adjusted at intervals of at as have nausea, vomiting, and gastro-intestinal discom- least 4 weeks; max. 80 mg once daily at night

fort. Hypertriglyceridaemia may be aggravated. An Note Max. 10 mg daily with concomitant ciclosporin, danazol,

increased bleeding tendency has been reported due to fibrate or lipid-lowering dose of nicotinic acid. Max. 20 mg daily with concomitant amiodarone or verapamil. Max. 40 mg daily

hypoprothrombinaemia associated with vitamin K defi- with diltiazem

ciency.

1 Simvastatin (Non-proprietary) A , simvastatin 10 mg, net price 28-tab pack =

Counselling Tablets Other drugs should be taken at least 1 85p, 20 mg, 28-tab pack = 95p; 40 mg, 28-tab pack =

hour before or 4–6 hours after bile acid sequestrants to £1.37; 80 mg, 28-tab pack = £2.94. Counselling,

reduce possible interference with absorption. Coleseve- muscle effects, see notes above

lam and a statin can be taken at the same time. Brands include Simvador

1 Zocor c (MSD) A Tablets , all f/c, simvastatin 10 mg (peach), net price

COLESEVELAM HYDROCHLORIDE

28-tab pack = £18.03; 20 mg (tan), 28-tab pack = £29.69; 40 mg (red), 28-tab pack = £29.69; 80 mg (red), Indications primary hypercholesterolaemia as an 28-tab pack = £29.69. Counselling, muscle effects, see

adjunct to dietary measures, either alone or with a notes above

statin Cautions see notes above; also gastro-intestinal moti-

With ezetimibe lity disorders, major gastro-intestinal surgery, Note For hypercholesterolaemia in patients stabilised on the

inflammatory bowel disease, hepatic impairment; individual components in the same proportions, or for patients

pregnancy (Appendix 4); breast-feeding (Appendix 5) not adequately controlled by statin alone. The Scottish Medi-

Contra-indications bowel or biliary obstruction cines Consortium has advised (June 2005) that Inegy is accepted for restricted use for patients not adequately

Side-effects see notes above; also headache; myalgia controlled with a maximal dose of a statin. For cautions, contra-

Dose

indications, and side-effects of ezetimibe, see Ezetimibe . Monotherapy, 3.75 g daily in 1–2 divided doses; max.

Inegy c (MSD, Schering-Plough) TA

4.375 g daily

ardiov C

Tablets , simvastatin 20 mg, ezetimibe 10 mg, net price . Combination therapy with statin, 2.5–3.75 g daily in

28-tab pack = £33.42; simvastatin 40 mg, ezetimibe

1–2 divided doses

10 mg, 28-tab pack = £38.98; simvastatin 80 mg, eze- Cholestagel timibe 10 mg, 28-tab pack = £41.21. Counselling, c (Genzyme) TA

ascular

muscle effects, see notes above Tablets , f/c, colesevelam hydrochloride 625 mg, net price 180-cap pack = £92.66. Label: 21, counselling, avoid other drugs at same time (see notes above)

syst Bile acid sequestrants

em

Colesevelam, colestipol, and colestyramine (choles- tyramine) are bile acid sequestrants used in the manage-

COLESTYRAMINE

ment of hypercholesterolaemia. They act by binding bile (Cholestyramine) acids, preventing their reabsorption; this promotes

Indications hyperlipidaemias, particularly type IIa, in hepatic conversion of cholesterol into bile acids; the

patients who have not responded adequately to diet resultant increased LDL-receptor activity of liver cells

and other appropriate measures; primary prevention increases the clearance of LDL-cholesterol from the

of coronary heart disease in men aged 35–59 years plasma. Bile acid sequestrants effectively reduce LDL-

with primary hypercholesterolaemia who have not cholesterol but can aggravate hypertriglyceridaemia.

responded to diet and other appropriate measures; The Scottish Medicines Consortium (p. 3) has advised

pruritus associated with partial biliary obstruction and (January

primary biliary cirrhosis (section 1.9.2); diarrhoeal (Cholestagel c

2008) that colesevelam

hydrochloride

) is not recommended for use within disorders (section 1.9.2) NHS Scotland for the treatment of primary hyper-

Cautions see notes above; pregnancy (Appendix 4); cholesterolaemia as an adjunct to dietary measures,

breast-feeding (Appendix 5); interactions: Appendix either alone or with a statin.

1 (colestyramine) Contra-indications complete biliary obstruction (not Cautions Bile acid sequestrants interfere with the

likely to be effective) absorption of fat-soluble vitamins; supplements of vita-

Side-effects see notes above; intestinal obstruction mins A, D, and K may be required when treatment is

reported rarely and hyperchloraemic acidosis prolonged. Interactions: Appendix 1 (bile acid seques-

reported on prolonged use trants)

Dose . Lipid reduction, initially 4 g daily increased by 4 g at

Side-effects

As bile acid sequestrants are not weekly intervals to 12–24 g daily in 1–4 divided doses, absorbed, gastro-intestinal side-effects predominate.

then adjusted as required; max. 36 g daily 1. Simvastatin 10 mg tablets can be sold to the public to

. Pruritus, see section 1.9.2 reduce risk of first coronary event in individuals at

. Diarrhoeal disorders, see section 1.9.2 moderate risk of coronary heart disease (approx. 10–15%

. CHILD 6–12 years, see BNF for Children risk of major event in 10 years), max. daily dose 10 mg and pack size of 28 tablets; treatment should form part of a

Note The contents of each sachet should be mixed with at least programme to reduce risk of coronary heart disease; a

150 mL of water or other suitable liquid such as fruit juice, proprietary brand Zocor Heart-Pro is on sale to the public

skimmed milk, thin soups, and pulpy fruits with a high moisture content

2.12 Lipid-regulating drugs BNF 57 Colestyramine (Non-proprietary) A

EZETIMIBE

Powder , sugar-free, colestyramine (anhydrous) 4 g/

sachet, net price 50-sachet pack = £18.20. Label: 13, Indications adjunct to dietary measures and statin counselling, avoid other drugs at same time (see notes

treatment in primary hypercholesterolaemia and above)

homozygous familial hypercholesterolaemia (ezeti-

Excipients include aspartame (section 9.4.1)

mibe alone in primary hypercholesterolaemia if statin

c Questran inappropriate or not tolerated); adjunct to dietary (Bristol-Myers Squibb) A measures in homozygous sitosterolaemia Powder , colestyramine (anhydrous) 4 g/sachet, net

Cautions hepatic impairment (avoid if moderate or price 50-sachet pack = £11.42. Label: 13, counselling,

severe; Appendix 2); pregnancy (Appendix 4); breast- avoid other drugs at same time (see notes above) Excipients include sucrose 3.79g/sachet

feeding (Appendix 5); interactions: Appendix 1 (eze- timibe)

Questran Light c (Bristol-Myers Squibb) A Side-effects gastro-intestinal disturbances; headache, Powder , sugar-free, colestyramine (anhydrous) 4 g/

fatigue; myalgia; rarely arthralgia, hypersensitivity sachet, net price 50-sachet pack = £16.99. Label: 13,

reactions (including rash, angioedema, and anaphy- counselling, avoid other drugs at same time (see notes

laxis), hepatitis; very rarely pancreatitis, cholelithiasis, tem cholecystitis, thrombocytopenia, raised creatine above)

Excipients include aspartame (section 9.4.1)

kinase, myopathy, and rhabdomyolysis

sys

Dose . ADULT and CHILD over 10 years, 10 mg once daily

Ezetrol COLESTIPOL HYDROCHLORIDE c (MSD, Schering-Plough) TA

ascular

Tablets Indications , ezetimibe 10 mg, net price 28-tab pack = hyperlipidaemias, particularly type IIa, in

diov £26.31

C ar

patients who have not responded adequately to diet and other appropriate measures

With simvastatin Cautions see notes above; pregnancy (Appendix 4);

2 See under Simvastatin

breast-feeding (Appendix 5); interactions: Appendix

1 (colestipol) Side-effects see notes above

Fibrates

Dose Bezafibrate, ciprofibrate, fenofibrate, and gemfibrozil . Initially 5 g 1–2 times daily in liquid increased if

act mainly by decreasing serum triglycerides; they have necessary in 5-g increments at intervals of 1 month to

variable effects on LDL-cholesterol. Although a fibrate max. 30 g daily (in 1–2 divided doses)

can reduce the risk of coronary heart disease events in Note The contents of each sachet should be mixed with at least

those with low HDL-cholesterol or with raised tri- 100 mL of water or other suitable liquid such as fruit juice, skimmed milk, thin soups, yoghurt, and pulpy fruits with a high

glycerides, a statin should be used first. Fibrates are moisture content

first-line therapy only in those whose serum-triglyceride concentration is greater than 10 mmol/litre or in those Colestid c (Pharmacia) A who cannot tolerate a statin. In type 2 diabetes a fibrate

Granules , yellow, colestipol hydrochloride 5 g/sachet, can be added to a statin for those with a serum-trigly- net price 30 sachets = £15.05. Label: 13, counselling,

ceride concentration exceeding 2.3 mmol/litre, despite avoid other drugs at same time (see notes above)

6 months of treatment with a statin and optimal glycae- Colestid Orange , granules, yellow/orange, colestipol

mic control.

hydrochloride 5 g/sachet, with aspartame, net price Fibrates can cause a myositis-like syndrome, especially

30 sachets = £15.05. Label: 13, counselling, avoid if renal function is impaired. Also, combination of a other drugs at same time (see notes above)

fibrate with a statin increases the risk of muscle effects (especially rhabdomyolysis) and should be used with caution (see CSM advice on p. 140) and monitoring of

Ezetimibe liver function and creatinine kinase should be consid-

ered; gemfibrozil and statins should not be used con- Ezetimibe inhibits the intestinal absorption of choles-

comitantly.

terol. It is licensed as an adjunct to dietary manipulation in patients with primary hypercholesterolaemia in com- bination with a statin or alone (if a statin is inappropri-

BEZAFIBRATE

ate), in patients with homozygous familial hyper- Indications hyperlipidaemias of types IIa, IIb, III, IV, cholesterolaemia in combination with a statin, and in

and V in patients who have not responded adequately patients with homozygous familial sitosterolaemia (phy-

to diet and other appropriate measures; also see notes tosterolaemia). If ezetimibe is used in combination with

above

a statin, there is an increased risk of rhabdomyolysis Cautions correct hypothyroidism before initiating (see also CSM advice on p. 140).

treatment (see p. 140); hepatic impairment (avoid if severe; Appendix 2); renal impairment (avoid if

NICE guidance creatinine clearance less than 15 mL/minute; Ezetimibe for the treatment of primary

Appendix 3; see also under Myotoxicity below); hypercholesterolaemia (November 2007)

interactions: Appendix 1 (fibrates) Ezetimibe, used in accordance with the licensed

Myotoxicity Special care needed in patients with renal indications for Ezetrol c , is an option for the

disease, as progressive increases in serum creatinine con- centration or failure to follow dosage guidelines may result in

treatment of adults with primary hypercholesterol- myotoxicity (rhabdomyolysis); discontinue if myotoxicity aemia.

suspected or creatine kinase concentration increases signif- icantly

BNF 57

2.12 Lipid-regulating drugs 145

Contra-indications hypoalbuminaemia, primary Contra-indications gall bladder disease; photosensit- biliary cirrhosis, gall bladder disease, nephrotic

ivity to ketoprofen; severe hepatic impairment syndrome, pregnancy (Appendix 4); breast-feeding

(Appendix 2); pregnancy (Appendix 4); breast-feeding (Appendix 5)

(Appendix 5)

Side-effects gastro-intestinal disturbances, anorexia; Side-effects see under Bezafibrate; also very rarely less commonly cholestasis, weight gain, dizziness,

hepatitis, pancreatitis, and interstitial pneumopathies headache, fatigue, drowsiness, renal impairment,

Dose

raised serum creatinine (unrelated to renal impair- . See preparations below ment), erectile dysfunction, myotoxicity (with myas-

thenia or myalgia)—special risk in renal impairment Fenofibrate (Non-proprietary) A (see Cautions), urticaria, pruritus, photosensitivity

Capsules , fenofibrate (micronised) 200 mg, net price reactions; very rarely gallstones, hypoglycaemia,

28-cap pack = £14.23. Label: 21 anaemia, leucopenia, thrombocytopenia, increased

1 capsule daily (dose form not appropriate for children or platelet count, alopecia, Stevens-Johnson syndrome,

Dose

in renal impairment)

and toxic epidermal necrolysis Capsules , fenofibrate (micronised) 267 mg, net price Dose

28-cap pack = £21.75. Label: 21 . See preparations below

Dose severe hyperlipidaemia, 1 capsule daily (dose form not appropriate for children or in renal impairment)

Bezafibrate (Non-proprietary) A Tablets , bezafibrate 200 mg, net price 100-tab pack =

Lipantil c c (Solvay) A £11.23. Label: 21

Lipantil Micro 67 capsules , yellow, fenofibrate Dose 200 mg 3 times daily; CHILD over 10 years, see BNF for

(micronised) 67 mg, net price 90-cap pack = £23.30. Children

Label: 21

c Dose Bezalip initially 3 capsules daily in divided doses; usual range 2–4 (Roche) A capsules daily; CHILD 4–15 years 1 capsule/20 kg daily Tablets , f/c, bezafibrate 200 mg, net price 100-tab

Lipantil pack = £9.15. Label: 21 c Micro 200 capsules , orange, fenofibrate Dose 200 mg 3 times daily; CHILD

(micronised) 200 mg, net price 28-cap pack = £17.95. over 10 years, see BNF for Children

Label: 21 Dose initially 1 capsule daily (dose form not appropriate for

Modified release children or in renal impairment)

ardiov

Lipantil Bezafibrate c (Non-proprietary) A Micro 267 capsules , orange/cream, feno-

Tablets , m/r, bezafibrate 400 mg, net price 28-tab fibrate (micronised) 267 mg, net price 28-cap pack = pack = £7.68. Label: 21, 25

£21.75. Label: 21

ascular

Dose 400 mg once daily (dose form not appropriate in patients Dose severe hyperlipidaemia, 1 capsule daily (dose form not with renal impairment)

appropriate for children or in renal impairment) Brands include Fibrazate XL , Zimbacol

XL

Supralip c c 160 (Solvay) A syst

Bezalip Mono (Roche) A Tablets , f/c, fenofibrate (micronised) 160 mg, net Tablets , m/r, f/c, bezafibrate 400 mg, net price 30-tab

price 28-tab pack = £14.75. Label: 21

em

pack = £8.09. Label: 21, 25 Dose 160 mg daily (dose form not appropriate for children or in Dose 400 mg once daily (dose form not appropriate in patients

renal impairment)

with renal impairment)