Etacrynic Acid/Ezetimibe 1379
unchanged and partly in the form of metabolites. It is Efortil; Etilefril; Chile: Elfortilt; Fin.: Elfortil; Fr.: Effortil; Ger.: over 10 years, may be given ezetimibe for the same indica extensively bound to plasma proteins. Bioflutin; Effortil; Etil; Pholdyston; Thomasin; Gr.: Effortil; tions and at the same doses as in adults (see above). ' Efortil; Ita/. : Elfortil; Jpn: Effortil; Mex.: Effortil; Quimtatil; Pol.: Effortil; Port.: Effortil; S.Afr.: Effortilt; Spain: Efortil; Swed.: Hyperlipidaemias. Ezetimibe inhibits the absorption of �:.�!?.�.��.!��-��--·········································································· Effortil; Switz. : Effortil; Thai.: Buracard; Circula; Circuman; dietary cholesterol' and, although there is a compensatory Proprietary Preparations (details are given in Volume B) Venez. : Elfortilt; Effrine; Efxine; Hyposia; Hyprosiat; Effontil. increase in cholesterol synthesis in the liver.' overall Single-ingredient Preparations. Austral.: Edecrin; Canad.: Multi-ingredient Preparations. Austria: Agilan; Amphodynt; plasma LDL-cholesterol concentrations are reduced.2 Ezeti Edecrin; Hung.: Uregyt; Ita!. : Reomax; Rus.: Uregyt (Ypei"HT); Effortil camp; Hypodynt; Influbenet; Ger.: Dibydergot plus; mibe may be used alone' in the management of hyperlipi Ukr.: Uregyt (YperHT); USA: Edecrin. Effortil plust; Switz.: Dibydergot plust; Elfortil plust. daentias (p. 1248.1) but use with lipid regulating drugs Phannacopoeial Preparations that act by reducing cholesterol synthesis may produce BP 2014: Sodium Etacrynate Injection; additive effects. In patients already taking statins, addition USP 36: Ethacrynate Sodium for Injection; Ethacrynic Add Etofibrate(riNNJ of ezetintibe results in a further reduction in LDL-choles terol, 4 which may increase the number of patients achiev ing lipid targets, or allow lower doses of statins to be used. However, the clinical relevance of this is unclear; a study' in patients with familial hypercholesterolaemia found no difference in the progression of carotid atherosclerosis (measured by intima-media thickness) in those given eze tintibe with simvastatin compared with those given simva statin alone, despite a larger reduction in LDL-cholesterol. Sintilar effects on LDL-cholesterol have been reported6 for ezetimibe with fibrates. As well as inhibiting cholesterol absorption, ezetintibe also blocks the absorption of plant sterols such as Etofibrate, a derivative of clofibrate (p. 1338.3) and carnpesterol and sitosterol, and may be effective in patients Profile nicotinic add (p. 2083.1), is a lipid regulating drug used in with sitosterolaentia,7 an inherited disorder in which the treatment of hyperlipidaentias (p. 1248,1). The usual increased absorption of plant sterols leads to premature Ethadzine, an analogue of moracizine (p. 1441.2), is oral dose is SOOmg daily. atherosclerosis. reported to be a class Ic antiarrhythntic. It is used in the 1, Sudhop T, et al. Inhibition of intestinal cholesterol absorption by treatment of ventricular and supraventricular arrhythntias ezetimibe in humans. Circulation 2002; 106: 1943-8. and has been given orally in doses starting at SO mg three �-��-��!����---········································································· 2. Knopp RH, et al. Effects of ezetimibe, a new cholesterol absorption times daily, increased if necessary to a maximum of 100mg Proprietary Preparations (details are given io Volume E) inhibitor. on plasma lipids in patients with primary hypercholester olemia. Bur Heart J 2003; 24: 729-41. three times daily. It has also been given intravenously. Single-ingredient Preparations. Braz. : Tricero� Ger.: Lipo-Merzt; 3. Pandor A, etal. Ezetimibe monotherapy for cholesterol lowering in 2, 722 Hong Kong: Lipo-Merz; Port,: Lipo-Merz. people: systematic review and meta-analysis of randomized controlled trials. J Intern Med 2009; 265: 568-80. 4. Pearson TA, et al. A community-basecl randomized trial of ezetimibe added to statin therapy to attain NCEP ATP m goals for LDL cholesterol in hypercholesterolemic patients: the ezetimibe add-on to statin for .effectiveness (EASE) trial. Mayo Clin Proc 2005; 80: 587-95. 5. Kastelein JJP, et al. The ENHANCE Investigators. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Eng! J Med 2008; 358: 1431-43. 6. McKenney JM, et al. Safety and efficacy of long-term co-administration of fenofibrate and ezetimibe in patients with mixed hyperlipidemia. J Am Col/ Cardiol 2006; 47: 1584-7. 7. Salen G, et al. Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia. Circulation 2004; 109: 966--71. Adverse Effects and Precautions Ezethnibe is generally well tolerated. The most common adverse effects include headache, abdominal pain, and Etofylline clofibrate, a fibric add derivative (see Bezafibrate, diarrhoea; other gastrointestinal disorders, hypersensitivity Pharmacopoeias. In Eur. (see p. vii) and Jpn. p. 1323.2), is a lipid regulating drug that has been used in reactions including rash and angioedema, fatigue, chest Ph. Bur. 8: (Etilefrine Hydrochloride). A white or almost the treatment of hyperlipidaentias (p. 1248. 1). An oral dose pain, and arthralgia have also been reported. Rare adverse white, crystalline powder or colourless crystals. Freely of 250 mg two or three thnes daily has been given. effects include raised liver enzymes or hepatitis, pancreat soluble in water; soluble in alcohol; practically insoluble in itis, thrombocytopenia, cholelithiasis, and cholecystitis. dichloromethane. Store in airtight containers. Protect from �:.��-��t����············································································ Myalgia has occurred in patients taking ezetimibe either light. alone or when added to a statin (see Effects on Skeletal Proprietary Preparations (details are given in Volume B) Muscle, p. 1380.1). Ezetimibe should be stopped if Profile Single-ingredient Preparations. Cz. : Duolipt; Ger.: Duolipt; myopathy is suspected or creatine phosphokinase increases Hong Kong: Duolipt. significantly. Etilefrine is a direct-acting sympathontimetic (p. 1507.3) Ezetimibe should be avoided in patients with moderate with beta -agonist properties, and some alpha- and betar 1 or severe hepatic impairment. agonist actions. It is used for the treatment of hypotensive (BAN, USAN, r/NN) states (p. 1277.2). It is given orally as the hydrochloride in E:zetimibe Reviews. usual doses of 5 or 10 mg three times daily; modified-release l. Jacobson TA, et al. Safety considerations with gastrointestinally active lipid-lowering drugs: Am J Cardiol 2007; 99 (Issue 6 suppl l): 47C-55C. dosage forms may be given in doses of 2 5 mg once or twice 2. Kashani A, et al. Review of side-effect profile of combination ezetimibe daily. Etilefrine hydrochloride can also be given parent and statin therapy in randomized clinical trials. Am J Cardio/ 2008; 101: erally. 1606-13. Etilefrine polistirex has been used in the management of rhinitis. Carcinogenicity. Statins are not thought to cause cancer (for a discussion, see Malignant Neoplasms under Uses Parphyria. The Drug Database for Acute Porphyria, com and Adntinistration of Simvastatin, p. 1491.3). However, piled by the Norwegian Porphyria Centre (NAPOS) and an excess of incident cancer and fatal cancer was seen 1 in the Porphyria Centre Sweden, classifies etilefrine as prob patients given combination therapy with simvastatin and ably not porphyrinogenic; it may be used as a drug of first Uses and Administration ezetintibe when compared with placebo. To better exam choice and no precautions are needed.1 ine the association, the data were pooled with those of 1. The Drug Database for Acute Porphyria. Available at: http:/lwww. Ezetimibe is an inhibitor of intestinal sterol absorption and two large, uncompleted studies;2 the authors concluded drugs-porphyria.org (accessed 18110/11) inhibits the absorption of cholesterol and plant sterols. It is that there was no evidence that the combination caused used to reduce total cholesterol, low-density lipoprotein cancer, a conclusion that has been criticised.'·' Neither the Priapism. Priapism is a common complication of sickle-cell (LDL)-cholesterol, and apolipoprotein Bin the management FDA6 nor MHRA7 considered that a conclusion could be disease (p. 1123.2) and is often treated with intracavemo of hyperlipidaentias (below), and to reduce sitosterol and drawn as to the effect of ezetimibe on cancer. carnpesterol in patients with homozygous fantilial sitoster sal alpha agonists (see under Uses of Metarantinol, 1. Rosseb0 AB, et a!. SEAS Investigators. Intensive lipid lowering with p. 1430.2). There have also been reports of the successful olaemia. It is given orally in a usual dose of 10 mg once simvastatin and ezetimibe in aortic stenosis. N Engl J Med 2008; 359: use of etilefrine, both by intracavemosal injection for daily. 1343-56. acute treatment, 1•2 and orally for prophylaxis 1·3 For use in children, see below. 2. Peto R, etal. Analyses of cancer data from three ezetimibe trials. N Eng! J Med 2008; 359: 1357-66. 1. Virag R, et al. Preventive treatment of priapism in sickle cell disease with Reviews. 3. Drazen JM, et al. Ezetimibe and cancer-an uncertain association. N Eng! oral and self-administered intracavemous injection of etilefrine. Urology 1. Sudhop T, von Bergmann K. Cholesterol absorption inhibitors for the J Med 2008; 359: 1398-9. 1996; 47: 777-81. treatment of hypercholesterolaemia. Drugs 2002; 62: 2333-47. 4. Nissen SE. Analyses of cancer data from three ezetimibe trials. N Eng! J 2. Gbadoe AD, et al. Management of sickle cell priapism with etilefrine. 2. Mauro VF, Tuckerman CE. Ezetimibe for management of hypercholes Med 2009; 360: 86-7. Arch Dis Child 2001; 85: 52-3. terolemia. Ann Pharmacother2003; 37: 839-48. 5. Fleming TR. Identifying and addressing safety signals in clinical trials. N 3. Okpala I, et a!. Etilefrine for the prevention of priapism in adult sickle cell 3. Bays HE, et al. Ezetimibe: cholesterol lowering and beyond. Expert Rev Eng! J Med 2008; 359: 1400-2. disease. Br J Haematol 2002; 118: 918-21. Cardiovasc Ther 2008; 6: 447-70. 6. FDA. Early communication about an ongoing safety review of 4. Anonymouse. Ezetimibe-an update. Drug Ther Bul1 2009; 47: 91-5. ezetimibe/simvastatin (marketed as Vytorin), simvastatin (marketed as ti Zocor) and ezetimibe (marketed as Zetia) (issued 21st August 2008). �:.�P.�.��- ���---········································································· Administralian in children. Experience with ezetintibe in Available at: http://www.fda.gov/Drugs/DrugSafety/ Proprietary Preparations (details are given in Volume B) children is lintited, but UK licensed product information PostmarketDrugSafetylnformationforPatientsandProviders/ uonl62899.htm (accessed 12/06/09) Single-ingredient Preparations. Arg,: Corcanfol; Effortil; Etil states that adolescent boys of Tanner stage II and above, 7. MHRA/CHM. Ezetimibe and results of SEAS study: possible increased Adriano!; Menegradil; Austria: Effortil; Belg, : Effortil; Braz.: and girls at least I year post-menarche, and who are aged risk of cancer. Drug Safety Update 2008; 2 (4): 7. Available at: http:fl
The symbol t denotes a preparation no longer actively marketed The symbol 0 denotes a substance whose use may be restricted in certain sports (see p. viii) 1380 Cardiovascular
www.mhra.gov.uk/home/idcplg?IdcService""GET_Fll..E&dDocName= excreted primarily in the faeces via bile and undergoes CON030924&RevisionSelectionMethod=LatestReleased (accessed enterohepatic recycling; after an oral dose, about 78% is 12/06/09) excreted in the faeces, mainly as ezetimibe, and about 11% Proprietary Preparations (details are given in Volume B) Effects on the liver. Ezetimibe may cause an increase in is excreted in the urine, mainly as the glucuronide. The Single-ingredient Preparations. China: Chuanwei (}I IlliG);Eril (i& liver enzymes and there have also been reports of acute elimination half-life for both ezetimibe and the glucuronide :s'LP);Jp n: Eril. hepatitis, L2 sometimes developing after addition of ezeti is about 22 hours. Ezetimibe is distributed into breast milk in rnibe to long-term statin therapy.3A Both auto-immune3A rats. and cholestatic hepatitis4 have been described. In some Reviews Felodipine raAN. usAN. riNNI patients, J-3 symptoms resolved and liver enzymes normal L Kosoglou T, et a!. Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet 2005; 44: ised when ezetimibe was stopped, and in 1 patient a statin 467-94. was successfully restarted. 3 However, of 2 patients who had been receiving ezetimibe and atorvastatin, 1 required treatment with corticosteroids,4 while the other" had per sistent liver changes 4 months later, despite both drugs Proprietary Preparations (details are given in Volume B) being stopped in eacb case. I. Liu Q, et a!. Drug-induced liver injuryassociated with ezetimibe therapy. Single-ingredient Preparations. Arg. : Acotral; Alin; Alipas; Cer Dig Dis Sci 2007; 52: 602-5. clerol; Cetrakamt; Coracil; Enediex; Ezetrol; Ixacor; Lipimibet; 2. Castellote J, et a!. Serious drug-induced liver disease secondary to Nalecol; Sinterol; Trilip; Vadel; Zetia; Austral.: Ezetrol; Austria: ezetimibe. World 1 Gastroenterol 2008; 14: 5098-9. Ezetrol; Belg. : Ezetrol; Braz.: Ezetrol; Zetia; Canad.: Ezetrol; 3. van Heyningen C. Drug-induced acute autoimmune hepatitis during Chile: Ezetrol; Zient; China: Ezetrol Cz.: Ezetrol; Pharmacopoeias. In Chin., Bur. (see p. vii), and US. combination therapy with atorvastatin and ezetimibe. Ann Clin Biochem (ihl.Jl1t�); 2005; 42: 402-4. Zientt; Denm.: Ezetrol; Fin.: Ezetrol; Fr. : Ezetrol; Ger.: Ezetrol; Ph. Eur. 8: (Felodlpine). A white or light yellow, crystalline 4. Stolk MF, et al. Severe hepatic side effects of ezetimibe. Clin Gastroenterol Gr.: Ezetrol; Hong Kong: Ezetrol; Hung.: Ezetrol; India: Esia; powder. Practically insoluble in water; freely soluble in Hepato/ 2006; 4: 908-1 1. Ezedoc; Ezentia; Ezerem; Ezetibt; Ezibloc; Ezta; Ezzicad; dehydrated alcohol. in acetone, in dichloromethane, and in Imbibet; Lipezet; Mibe; Indon.: Ezetrol; Irl.: Ezetrol; Israel: methyl alcohol. Protect from light. Effects on the pancreos. Pancreatitis has been reported' in Ezetrol; Ital.: Ezetrol; Zetia; Malaysia: Ezetrol; Mex. : Ezetrol; patients taking ezetimibe. In one case, 2 acute pancreatitis Zient; Neth.: Ezetrol; Norw.: Ezetrol; NZ: Ezetrol; Philipp_: Eze� USP 36: (Felodipine). A light yellow to yellow, crystalline developed 2 weeks after starting ezetimibe and re�olvcd trol; Pol.: Ezetrol; Port.: Adacai; Ezetrol; Rus_: Ezetrol powder. Insoluble in water; freely soluble in acetone and in when the drug was stopped, suggesting an immunological (33eTpon); S.Afr. : Ezetrol; Singapore: Ezetrol; Spain: Absorcol; methyl alcohol; very slightly soluble in heptane. Store in cause. Ezetrol; Swed.: Ezetrol; Switz.: Ezetrol; Thai. : Ezetrol; Turk.: airtight containers. Protect from light. Colebyn; Ezetrol; Kolez; UK: Ezetrol; USA: Zetia; Venez. : Eze� Adverse Drug Reactions Advisory Committee (ADRAC). Drug induced l. trol; Zetia; Zient. pancreatitis. Aust Adverse Drug React Bull 2006; 25: 22. Also available at: Uses and Administration http://www .tga.gov .au/adr/aadrb/aadr0612.pd.f (accessed 30/05/08) 2. Ahmad I, Ezetimibe-induced acute pancreatitis. 2007; Multi�ingredient Preparations. Arg.: Alipas Duo; Ampliar Duo; et a!. South Med 1 Felodipine is a dihydropyridine calcium-channel blocker 100: 409-10. Ampliar Plus; Ateroclar Combi; Ateroclar Duo; Coleflux Duo; with actions similar to those of nifedipine (p. 144 7.2). It is Colmibe; Craveril Duo; Labistatin Duo; Liparex Duo; Liparex used in the management of hypertension (p. 12 51.1) and Effects on skeletal muscle. Muscle disorders such as myal Plus; Lipibec Duo; Lipibec Plus; Lipocambi Plus; Liponorm Duo; angina pectoris (p. l2 54.3). gia and myopathy are well known to occur with lipid reg Minuslip Duo; Plan Duo; Redusterol Duo; Salvaxil Plus; Sinter Felodipine is given orally, generally in a modified-release ulating drugs such as statins and fibrates and have also ol Compuesto; Torimibe; Vasotenal EZ; Vytorin; Zimetek; Aus formulation for use once daily in the morning. In tral.: Vytorin; Austria: Inegy; Belg.: Inegy; Braz.: Vytorin; Zet been reported with ezetimibe, both alone, u and when hypertension the usual initial dose is 5 mg daily, adjusted added to treatment with statins; I.3 rhabdomyolysis has sim; Chile: Adacai; Vytorin; Zintrepid; China: Vytorin (::w;�IJb; Cz.: Inegy; Denm.: Inegy; Fin.: Inegy; Fr.: Inegy; Vytorin; Ger.: as required; the usual maintenance dose is 2.5 to 10mg daily also occurred, but is rare in patients taking ezetimibe and doses above 20 mg daily are not usually needed. In alone. Up to August 2005, the Australian Adverse Drug Inegy; Gr.: Inegy; Vytorin; Hong Kong: Vytorin; Hung.: Inegy; India: angina the usual initial dose is 5 mg daily increased if Reactions Advisory Committee4 had received 44 reports of Alnavas-EZ; Altovas-EZ; Aova-EZ; Atheart�EZ; Atherot wo; Atix-EZ; Atofast-EZ; Atorin-EZ; Atorlip-EZ; Atoroll-EZ; necessary to lO mg daily. muscle disorders with ezetimibe, including myalgia, Atortus-EZ; Atorvik-EZ; Avas EZ; Avascare-EZ; Aztor EZ; Bitor Lower doses may be required in patients with hepatic muscle cramp, weakness and pain; in 5 of these cases a va; Cardisoz-AT; Dilutex Plus; Dyslip-EZ; Dysliptin-EZ; Ecostat; impairment (see below) and in the elderly. statin was also being taken. Etovas-EZ; Ezemax-A; Ezevas; Fibator EZ; Genlip-EZ; Jvastor Reviews. I. Simard C, Poirier P. Ezetimibe-associated myopathy in monotherapy EZ; LDTor-Z; Lesstrol-EZ; Lipi-EZ; Lipikind-EZ; Lipivas EZ; Todd PA, Faulds D. Felodipine: a review of the pharmacology and and in combination with a 3-hydroxy-3-methylglutaryl coenzyme A l. Lipofix·EX; Liponorm-EZ; Lorlip·EZ; Modlip-EZ; Noclog-EZ; therapeutic use of the extended release formulation in cardiovascular reductase inhibitor. 2006; 141-4. Can J Cardiol 22: Omnitor-EZ; Orvaz-EZ; Zetitor; Indon_: Vytorin; Irl. : Inegy; disorders. Drugs 1992; 44: 251-77. 2. Havranek JM, et a!. Monotherapy with ezetimibe causing myopathy. Am Israel: Inegy; Ital. : Goltor; Inegy; Vytorin; Zeklen; Malaysia: 2. Walton T, Symes LR. Felod.ipine and isradipine: new calcium-channel J Med 2006; ll9: 285-6. blocking agents for the treatment of hypertension. Clin Pharm 1993; 12: Vytorin; Mex. : Vytorin; Zintrepid; Neth.: Inegy; Norw.: Inegy; 3. Fux R, et al. Ezetimibe and statio-associated myopathy. Ann InternMed 261-75. 2004; 140: 671-2. NZ: Vytorin; Philipp.: Vytorin; Port.: Inegy; Vytorin; Rus.: 4. Adverse Drug Reactions Advisory Committee (ADRAC). Ezetimibe and Inegy (llHe,Z:VKH); Singapore: Vytorin; Spain: Inegy; Vytorin; Administration in hepatic impairment. In 9 patients with muscle disorders. Aust Adverse Drug React Bull 2005; 24: 15. Also available Swed.: Inegy; Switz. : Inegy; Thai.: Vytorin; Turk : Inegy; UK: at: http://www .tga.health.gov .au/ adr/aadrb/aadr0508.pdf (accessed 1 Inegy; Ukr_: Azi-Ator (.A3H-Arop); USA: Liptruzet; Vytorin; liver cirrhosis given felodipine 750 micrograms by intra 30/05/08) Venez. : Adacai; Vytorin; Zintrepid. venous infusion over 20 minutes and 10 mg orally as sin gle doses on separate occasions the mean oral bioavailabil Porphyria. The Drug Database for Acute Porphyria, com ity was 17.1% which was not significantly different from piled by the Norwegian Porphyria Centre (NAPOS) and published values in healthy subjects, but the peak plasma the Porphyria Centre Sweden, classifies ezetimibe as prob Fasudil Hydrochloride (r!NNMI concentrations were almost twice as high as normal, ably not porphyrinogenic; it may be used as a drug of first Ch.forhydrate e; Fasudii. hidrodoruro apparently due to reduced systemic clearance and volume choice and no precautions are needed.1 AT-877; Fespdii� ·. d · de; Hyarochlorldum; HA 1Q77; Hidmdoruro d\" fasu d)l; of distribution.' The fact that bioavailability was not I. The Drug Database for Acute Porphyria. Available at: http://wvvw. Fasudili · increased suggests that much pre-systemic metabolism drugs-porphyria.org (accessed 19/10/11) illa3�A!1fla f14APO)(JiclpY>t\. . . · . · · . .·. ·•· < . . : . · . ·• . takes place in the gut rather than the liver. Although Hexahydro- -(5 -isoquinol !svlfOny. 0-1 H-1,4cdiazepine J y hydro increased adverse effects were not associated with the . · Interactions diloriqe .•.. •.. ·.· .. > . . ·. ... (};4H,,,I,!JD;S;Hm"'327,8 raised felodipine concentrations in this study it is recom Colestyramine reduces the absorption of ezetimibe and mended that therapy in cirrhotic patients begin at lower CAS ••• ·�.- _ . .J03.74S-.39:7 (fosUdiV; doses than in patients with normal liver function. US should not be given at the same time of day. Ciclosporin has cfiloride/. been reported to increase the plasma concentration of licensed product information recommends that an initial A'IP q04A)(J2 ezetimibe (see below) and patients receiving both drugs ':-- dose of 2.5 mg once daily should be used in patients with should be carefully monitored; the effect may be greater in Arc Vet .-c- QCQ4AX.32. hepatic impairment. patients with severe renal impairment. An increased INR UNfi ..:C:SQ04J\}85lBR. l. Regchdh CG, et a!. Pharmacokinetics of felodipine in patients with liver has been reported in patients given ezetimibe and oral disease. Bur J Clin Pharmaco! I989; 36: 473-9. anticoagulants. Profile Adverse Effects, Treatment, and Precautions ...... Ciclosporin. Pharmacokinetic studies' have shown that Fasudil is a selective inhibitor of Rho-kinase, a protein As for dihydropyridine calcium-channel blockers (see plasma -ezetimibe concentrations are higher in renal trans kinase involved in contraction of vascular smooth muscle. Nifedipine, p. 1450.2). plant patients taking ciclosporin than in historical controls, Fasudil is used as the hydrochloride hemihydrate for its and there has been a report2 of a supratherapeutic vasodilating properties in the management of cerebrovasc Porphyria. The Drug Database for Acute Porphyria, com response to ezetimibe in a heart transplant patient taking ular disorders including vasospasm after surgery for piled by the Norwegian Porphyria Centre (NAPOS) and ciclosporin. Ezetimibe causes a small increase in plasma subarachnoid haemorrhage. It is under investigation for the Porphyria Centre Sweden, classifies felodipine as prob ciclosporin concentrations, 3 but the clinical relevance of the treatment of angina pectoris, acute cerebral thromboSis, ably not porphyrinogenic; it may be used as a drug of first this is not clear. and pulmonary hypertension. choice and no precautions are needed. 1 1. Bergman et al. Interaction of single-dose ezetimibe and steady-state AJ. References. I. The Drug Database for Acute Porphyria. Available at: http:l/vvww. cyclosporine in renal transplant patients. J Clin Pharmacol 2006; 46: 328- drugs-porphyria.org (accessed 08/07/11) 36. I. Shibuya M, et al. Effect of AT877 on cerebral vasospasm after 2. Koshman SL, et al. Supratherapeutic response to ezetimibe administered aneurysmal subarachnoid hemorrhage: results of a prospective placebo with cyclosporine. Ann Pharmacother 2005; 39: 1561-5. controlled double-blind triaL J Neurosurg 1992; 76: 571-7. Interactions 3. Bergman AJ, et a/. Effects of ezetimibe on cyclosporine pharmacokinetics 2. Masumoto A, et al. Suppression of coronary artery spasm by the Rho in healthy subjects. J Clin Pharmacol 2006; 46: 321-7. kinase inhibitor fasudil in patients with vasospastic angina. Circulation As for dihydropyridine calcium-channel blockers (see 2002; 105: 1545-7. 3. Shimokawa H, et al. Anti-anginal effect of fasudil, a Rho-kinase Nifedipine, p. 1453.2). Pharmacokinetics inhibitor, in patients with stable effort angina: a multicenter study. J Cardiovasc Pharmacol 2002; 40: 751-61. Pharmacokinetics Ezetimibe is rapidly absorbed when given orally and 4. Vicari R.M, et al. Efficacy and safety of fasudil in patients with stable undergoes extensive conjugation in the small intestine and angina: a double-blind, placebo-controlled, phase 2 trial. J Am Colt Felodipine is almost completely absorbed from the liver to an active glucuronide metabolite, which is the main Cardiol 2005; 46: 1803-1 1. gastrointestinal tract after oral doses but undergoes 5. Suzuki Y, et al. A postmarketing surveillance study of fasudil treatment circulating form. Both ezetimibe and the glucuronide are after aneurysmal subarachnoid hemorrhage. Surg Neurol 2007; 68: 126- extensive first-pass metabolism, with a bioavailability of more than 90% bound to plasma proteins. Ezetinti.be is 3!. about 15% (range 10 to 25%). It is extensively metabolised
All cross-references refer to entries in Volume A