Table 11

 Compelling and possible indications, contraindications, and cautions for the major classes of lipid lowering drugs*

Class of drugCompelling indicationsPossible indicationsCaution*Compelling contraindications
*The specific product literature, prescribing information and licensed indications for each drug should be consulted in detail.
†Certain drugs metabolised through the cytochrome P450 3A4 pathway can significantly increase the plasma concentration of some of the statins. These include ciclosporin, conozole antifungals, calcium channel blockers, and amiodarone. Fluvastatin and ciclosporin are reported to have no adverse interactions.
‡A small increase in creatinine with fibrate therapy may not reflect clinically significant change. Gemfibrozil should not be used in this situation. Fenofibrate can be used with significant renal impairment, although some will reduce dose at creatinine >140 μmol/l and stop therapy at creatinine >160 μmol/l.
§Resins may bind other drugs and reduce their absorption. Other drugs should therefore be taken ⩾1 hour before or ⩾4 hours after the resin.
¶Gemfibrozil should not be used with statins. Fibrates may interfere with statin metabolism, increasing plasma statin levels, partly through the cytochrome P450 system and partly through other metabolic pathways including glucuronidation. Fenofibrate appears to be well tolerated without such major clinically significant interactions.
**Omega-3-acid ethyl esters (eicosapentaenoic, docosahexaenoic, and alpha-tocopherol) in the concentrated preparation (Omacor) are licensed at 1–2 g/day for CHD prevention, and at 2–4 g/day for treatment of hypertriglyceridaemia. Omega-3-marine triglycerides (in the preparation Maxepa in the dose of 5–10 g/day) are for the management of hypertriglyceridaemia.
HMG-CoA reductase inhibitors (statins)(1) Atherosclerotic cardiovascular disease(1) CVD 10–20% 10 years if:(1) Non-alcoholic steatohepatitis(1) Gemfibrozil¶
(i) Cholesterol/HDL ratio >6, or(2) Untreated hypothyroidism2. Significant liver disease (moderate transaminase elevation up to 3 times upper limit of normal may represent fatty change and not be a contraindication)
(2) (a) Type 1 and 2 diabetes mellitus aged 40 years or more(ii) LDL-C >5 mmol/l(3) Significant chronic renal impairment (creatinine > 160 μmol/l)
(b) Type 1 or 2 diabetes mellitus aged 18–39 years with specific indications: retinopathy, nephropathy, poor glycaemic control (HbA1c > 9%), elevated blood pressure requiring drug therapy, total cholesterol >6 mmol/l, features of metabolic syndrome, family history of premature CVD(4) Certain drugs metabolised through cytochrome P450, especially 3A4†
(5) Excess alcohol intake
(6) Grapefruit juice (in large amount) with statins metabolised through P450 3A4
(3) CVD risk ⩾20% 10 years
(4) Familial hypercholesterolaemia
Fibrates(1) Type III hyperlipoproteinemia (familial dysbetalipoproteinaemia, remnant lipaemia) (2) Severe hypertriglyceridaemia (>10 mmol/l) where there is a risk of pancreatitis(1) Type 2 diabetes mellitus with raised triglycerides and low HDL-C on specialist advice (2) Moderate-severe hypertriglyceridaemia with controlled LDL-C, and particularly elevated CVD risk on specialist advice(1) Chronic renal failure‡ (2) Concurrent statin therapy(1) Never use gemfibrozil with a statin¶
Anion exchange resinsNone (because of poor gastrointestinal tolerability)(1) Inadequate LDL-C control on statin and ezetimibe (e.g. familial hypercholesterolaemia)(1) Gastrointestinal upsetNone
(2) Exacerbation of hypertriglyceridaemia
(3) Interaction with other drugs§
(2) Cholestasis with itching(4) Reduction in fat soluble vitamin absorption (not normally clinically significant)
Nicotinic acid group (lipid regulating doses)(1) Severe hypertriglyceridaemia with prior acute pancreatitis (2) Type V (severe hypertriglyceridaemia not responsive to fibrates)In combination with other lipid regulating drugs to reduce both cholesterol and triglycerides. Most often used in mixed hyperlipidaemia(1) Other lipid lowering drugs (2) Impaired renal function (3) Liver disease (4) Diabetes mellitus (5) Gout (6) Peptic ulcer (7) Flushing, diarrhoea as side effects(1) Worsening glucose tolerance (2) Diarrhoea and/or flushing
Cholesterol absorption inhibitors(1) Familial sitosterolaemia(1) With a statin where LDL-C is not at target despite maximum licensed statin dose or maximum tolerated statin dose(1) Liver impairmentNone
(2) With fibrates except on specialist clinics
(2) Statin intolerance
Fish oils: omega-3-acid ethyl esters (eicosapentaenoic, docosahexaenoic and alpha-tocopherol); omega-3-marine triglycerides(1) Severe hypertriglyceridaemiaTreatment of hypertriglyceridaemia(1) AnticoagulantsNone (10 g/day of marine triglycerides carry a 90 calorie per day energy load)
(2) Haemorrhagic disorders
(2) CHD prevention**(3) Aspirin-sensitive asthma
(4) Diabetes mellitus