Drug reference
Milrinone is a phosphodiesterase type-3 inhibitor that exerts most effect on the myocardium; it has positive inotropic properties and vasodilator activity. Bile acid sequestrants act by binding bile acids, preventing their reabsorption; this promotes hepatic conversion of cholesterol into bile acids; the resultant increased LDL-receptor activity of liver cells increases the clearance of LDL-cholesterol from the plasma.
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Short-term treatment of severe congestive heart failure unresponsive to conventional maintenance therapy (not immediately after myocardial infarction) | Acute heart failure, including low output states following heart surgery ▶INITIALLY BY INTRAVENOUS INJECTION ▶Adult: Initially 50 micrograms/kg, given over 10 minutes, followed by (by intravenous infusion) 375–750 nanograms/kg/minute usually given following surgery for up to 12 hours or in congestive heart failure for 48-72 hours; maximum 1.13 mg/kg per day
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Severe hypovolaemia
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Correct hypokalaemia. heart failure associated with hypertrophic cardiomyopathy, stenotic or obstructive valvular disease or other outlet obstruction Interference with the absorption of fat-soluble vitamins (supplements of vitamins A, D, K, and folic acid may be required when treatment is prolonged).
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Sustained haemodynamic benefit has been observed after administration of phosphodiesterase type-3 inhibitors, but there is no evidence of any beneficial effect on survival.
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▶Common or very common Arrhythmia supraventricular (increased risk in patients with pre-existing arrhythmias). arrhythmias. headache. hypotension ▶Uncommon Angina pectoris. chest pain. hypokalaemia. thrombocytopenia. tremor ▶Rare or very rare Anaphylactic shock. bronchospasm. skin eruption ▶Frequency not known Renal failure ▶Common or very common Constipation. gastrointestinal discomfort. headache. nausea. vomiting ▶Uncommon Appetite decreased. diarrhoea. gastrointestinal disorders
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Manufacturer advises use only if potential benefit outweighs risk. Bile acid sequestrants should be used with caution as although the drugs are not absorbed, they may cause fat-soluble vitamin deficiency on prolonged use.
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Manufacturer advises avoid—no information available. Bile acid sequestrants should be used Cardiovascular system with caution as although the drugs are not absorbed, they may cause fat-soluble vitamin deficiency on prolonged use. eiiii F above
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Dose adjustments Reduce dose and monitor response if eGFR less than 50 mL/minute/1.73 m2—consult product literature for details.
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Monitor blood pressure, heart rate, ECG, central venous pressure, fluid and electrolyte status, renal function, platelet count and hepatic enzymes.
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Avoid extravasation. For intravenous injection, may be given either undiluted or diluted before use. For intravenous infusion (Primacor ®) give continuously in Glucose 5% or Sodium chloride 0.9%; dilute to a suggested concentration of 200 micrograms/mL.
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There can be variation in the licensing of different medicines containing the same drug. Forms available from special-order manufacturers include: solution for infusion Solution for infusion ▶Milrinone (Non-proprietary) Milrinone 1 mg per 1 ml Milrinone 10mg/10ml solution for infusion ampoules | 5 ampoule P £35.00 | 10 ampoule P £199.06 Milrinone 10mg/10ml concentrate for solution for infusion ampoules | 10 ampoule P s ▶Primacor (Sanofi) Milrinone 1 mg per 1 ml Primacor 10mg/10ml solution for injection ampoules | 10 ampoule P £199.06 Hyperlipidaemia Dyslipidaemias Hypercholesterolaemia and hypertriglyceridaemia Statins are the drugs of first choice for treating hypercholesterolaemia and moderate hypertriglyceridaemia. Severe hypercholesterolaemia or hypertriglyceridaemia not adequately controlled with a maximal dose of a statin may require the use of an additional lipid-regulating drug such as ezetimibe p. 210; such treatment should generally be supervised by a specialist. A number of conditions, some familial, are characterised by very high LDL-cholesterol concentration, high triglyceride concentration, or both. Although statins are more effective than other lipid-regulating drugs at lowering LDL-cholesterol concentration, they are less effective than fibrates in reducing triglyceride concentration. Fenofibrate p. 212 may be added to statin therapy if triglycerides remain high even after the LDL-cholesterol concentration has been reduced adequately. Familial hypercholesterolaemia Patients with familial hypercholesterolaemia are at high risk of premature coronary heart disease. g Lifelong lipid- modifying therapy and advice on lifestyle changes should be offered to all patients with familial hypercholesterolaemia. A high-intensity statin, defined as the dose at which a reduction in LDL-cholesterol of greater than 40% is achieved, is recommended as first-line therapy in all patients with familial hypercholesterolaemia. The dose of the statin should be titrated to achieve a reduction in LDL-cholesterol concentration of greater than 50% from baseline. Patients with primary heterozygous familial hypercholesterolaemia who have contra-indications to, or are intolerant of statins, can be considered for treatment with ezetimibe as monotherapy. A combination of a statin and ezetimibe is recommended if the maximum tolerated dose of a statin alone fails to provide adequate control of LDL- cholesterol, or a switch to an alternative statin is being considered. Treatment with a fibrate or a bile acid sequestrant (such as colestyramine p. 210 or colestipol hydrochloride p. 209) can be considered under specialist advice, in patients for whom statins or ezetimibe are inappropriate. The combination of a statin with a fibrate carries an increased risk of muscle-related side-effects (including rhabdomyolysis) and should be used under specialist supervision. The concomitant administration of gemfibrozil with a statin increases the risk of rhabdomyolysis considerably—this combination should not be used. Alirocumab p. 219 and evolocumab p. 219 can be considered for patients with primary heterozygous familial hypercholesterolaemia whose LDL-cholesterol has not been adequately controlled on maximum tolerated lipid-lowering therapy. h See National funding/access decisions information for alirocumab p. 219 and evolocumab p. 219. g The prescribing of drug therapy in homozygous familial hypercholesterolaemia should be undertaken in a specialist centre. h Reduction in low-density lipoprotein cholesterol Drug Therapy intensity Daily dose (reduction in LDL cholesterol) 20 mg (43%) High-intensity Atorvastatin 40 mg (49%) 80 mg (55%) 10 mg (43%) Rosuvastatin 20 mg (48%) 40 mg (53%) 80 mg (42%) Simvastatin 10 mg (37%) Medium-intensity Atorvastatin 80 mg (33%) Fluvastatin 5 mg (38%) Rosuvastatin 20 mg (32%) Simvastatin 40 mg (37%) 20 mg (21%) Low-intensity Fluvastatin 40 mg (27%) 10 mg (20%) Pravastatin 20 mg (24%) 40 mg (29%) 10 mg (27%) Simvastatin Advice from the MHRA: there is an increased risk of myopathy associated with high-dose (80 mg) simvastatin. The 80 mg dose should be considered only in patients with severe hypercholesterolaemia and high risk of cardiovascular complications who have not achieved their treatment goals on lower doses, when the benefits are expected to outweigh the potential risks. Other drugs used for Hyperlipidaemia Inositol nicotinate, p. 247 LIPID MODIFYING DRUGS › BILE ACID SEQUESTRANTS Bile acid sequestrants f
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Initially 50 micrograms/kg, given over
First-line fragment. Read the complete Indications and Dose section above.
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