tionamide with rifampicin and dapsone.3 A regimen of ograms/mL, the concentration considered by the authors rusAN, riNNJ protionamide, dapsone, rifampicin, and clofazimine has to be essential for therapeutic success. Fidaxomicin been associated with a 22% incidence based on laboratory I. Donald PR, Seifart Cerebrospinal fluid concentrations of ethion­ Pial;J:!P ici!la; Fida�ooiidne; . Fidaxt1 itina!J\; Ill. rry · Upia(!'fly n; 115: t!J tJ monitoring.4 Use of ethionamide with pyrazinamide has amide in children with tuberculous meningitis. Pediatr 1989; 483- PA�1Ql; .1)acumi<;:in.B; .· ·· 6. <ll'l!'ld�COMMt;l114• •... also resulted in a high incidence of abnormal liver func­ J (3E,5OPT-80;E;$5; 9E, 1 1 5,l2R; ,3-(f[�c[:)eo:xy-H)-/.' (3;':)­ tion tests.5 dichlo.ro'l'eth l-4,6"pi1 3/;',lhydSf,lS$)•[ o�ybe �oyn-:M'J- metl)yj.-�-o· In the above studies rifampicin was given daily during mannopyranpsyl)oxyy jmethy1)�1 :HL6·deo� xy-S'C�r)e hyk+i.h part or all of the regimens. The incidence of hepatotoxicity � ProprietaryPreparations (details are given in Volume B) (2'me!hylp:o�n<i>yl): -o-(Yxo- exopyrano y xy}�]·1 '��hyl­ when ethionamide or protionamide is used with once­ � � 9? .8-hydroxy- 18:-[(lR)-l -hydroxyethyll-t) 9, 13;15-trlmethytoxacy­ monthly rifampicin may be lower; hepatotoxicity was not Single-ingredient Preparations. Gr.: Trecator; India: E-Tbio; reported in patients receiving monthly rifampicin and daily Eniimide; Ethide; Ethimax; Ethiobin; Ethiocid; Ethiokox; Ethio­ doo<:taqec�-�.5,9,B;lS,pemaen -2-one. protionamide, isoniazid, and dapsone.6 nam; Ethomid; Etomide; Etumide; MDThide; Mycotuf; Myobid; C52H,.Cb0,s= Rus.: Ethide Ethomid (3-rOMiiJI): Myobid (Mno6ff)l); I. Pattyn SK et a!. Hepatotoxicity of the combination of rifampin­ 9A? .:....,. -,6),6105l.l .. Reginicid (PerHHHIJ;H.n;); S.Afr. : Ethatyl; Thai.: Eton; Turk. : Etyo­ ethionamide in the treatment of multibadllary leprosy. Int Lepr 1984; (3TH�); .. .• . _ !2. 52: 1-6. J mid; USA: Trecator. ATC:':"7 2. Pattyn SR, et a!. Combined regimens of one year duration in the 1\K \If;t-,- .9.'\0ZMJ:Z. treatment of multibadllary leprosy-II: combined regimens with Pharmacopoeial Preparations rifampicin administered during 6 months. Lepr Rev 1989; 60: 118--2 3. USP 36: Ethionamide Tablets. .UNit '""".ZS{'l076G8YQ 3. Cartel J-L, et al. Hepatitis in leprosy patients treated by a daily combination of dapsone, rifampin, and a thioamide. lnt Lepr 1983; 51: Uses and Administration 461-5. J 4. Ji B, et a!. Hepatotoxicity of combined therapy with rifampicin and daily Fidaxomicin is a nonabsorbed, narrow-spectrum macro­ prothionamide for leprosy. Lepr Rev 1984; 55: 283-9. cyclic antibacterial used in the treatment of Clostridium 5. Schiess JM, et a!. The use of ethionamide in combined drugregimens in difficile-associated diarrhoea (see Antibiotic-associated Col­ the re-treatment of isoniazid-resistant pulmonary tuberculosis. Am Rev itis, p. 183.1). It is given orally in a dose of 200mg twice Respir Dis 1965; 91: 728-37. 6. Ellard GA, et al. Long-term prothionamide compliance: a study carried daily for 10 days. out in India using a combined formulation containing prothionamide, 59: References. dapsone and isoniazid. Lepr Rev 1988; 163-75. l. Sullivan , Spooner LM. Fidaxomidn: a macrocyclic antibiotic for the Clostridium diffidle Ann Pharmacother 20 0; 44: managementKM of infection. I 352-9. Precautions 2. Miller M. Fidaxomicin (OPT-80) for the treatment of Clostridium difficile infection. Expert Opin Pharmacother 2010; 11: 1569-78. Ethionamide should not be used in - severe hepatic 3. et a!. Clostridium difficile Etimicin, a derivative of gentamicin C a, is an aminoglyco­ Louie TJ, Fidaxomicin versus vancomycin for impairment. Liver function tests should be carried out 1 infection. N Eng! Med 2011; 364: 422-31. side antibacterial with actions similar to those of gentamicin before, and regularly during, treatment with ethionamide. 4. Mullane KM, GorbachJ S. Fidaxomidn: first-in-class macrocyclic (p. 306.2). It is given intravenously as the sulfate. antibiotic. Expert Rev Anti Infect Ther 2011; 9: 767-77. Caution is necessary in patients with depression or other 5. Mullane KM, et a!. Efficacy of fidaxomicin versus vancomycin as therapy psychiatric illness. Difficulty may occur in the management for Clostridium dijfidle infection in individuals taking concomitant of diabetes mellitus. Periodic monitoring of blood glucose, Zhao C, et al. A randomized controlled clinical trial on etimicin, a new antibiotics for other concurrent infections. Clin Infect Dis 2011; 53: 44G-7. thyroid function, and visual function is desirable. aminoglycoside antibiotic, versus netilmicin in the treatment of bacterial infections. Chin Med (Eng!) 2000; 113: 1026-30. animals. Ethionamide is teratogenic in J Adverse Effectsand Precautions Adverse effects occurring with oral use of fidaxomicin are Interactions ProprietaryPreparations (details are given in Volume B) mainly gastrointestinal in nature and include nausea, The adverse effects of other antimycobacterials may be vomiting, and abdominal pain. Anaemia, neutropenia, and China: Yi (�fuE);Aida (�::k): increased when ethionamide is used (see Effects on the Single-ingredient Preparations. Ai gastrointestinal haemorrhage may also occur. Chuang Cheng Ge Mei Da Pan Nuo (iii!*): Liver, p. 297 .3, and under Cycloserine, Interactions, Since there is only minimal systemic absorption, oral XiNeng (;m;i!�);Yi Qing p. 281.1). (ilrJRJ<;); (�""it:); fidaxomicin should not be used for the treatment of (i!l'i/f). systemic infections. Use of oral fidaxomicin in the absence of ' a proven or strongly suspected Clostridium difficileinfection is Alcohol. A psychotic reaction has been reported in a unlikely to provide benefit and may lead to the patient receiving ethionamide after excessive intake of development of drug resistant bacteria. alcohol.' et at. L Lansdown FS, Psychotoxic reaction during ethionamide therapy. Am Rev Respir Dis 1967; 95: 1053-5. Antimicrobial Action Fidaxomicin has potent bactericidal activity against Clostridium difficile in vitro through its inhibition of RNA Antimicrobial Action synthesis by RNA polymerases. It has more limited activity Ethionamide is active only against mycobacteria including against other Gram-positive bacteria, and no activity against Mycobacterium tuberculosis, M. kansasii, M. leprae, M. Gram-negative bacteria. malmoense, and some strains of M. avium complex. Resistance develops rapidly if used alone and there is complete cross-resistance between ethionamide and Pharmacokinetics protionamide. Cross-resistance has also been reported Fidaxomicin is essentially nonabsorbed from the gastro­ with isoniazid and with in vitro thioacetazone. intestinal tract after an oral dose. It undergoes hydrolysis in the gut to form the main metabolite, OP-1118, which is microbiologically active. Over 92% of a dose is excreted in Cross-resistance. References. 1. Schaaf HS, et al. Ethionamide cross- and co-resistance in children with the faeces as either fidaxomicin or OP-118, although very isoniazid-resistant tuberculosis. lnt Tuberc Lung Dis 2009; 13: 1355-9. small amounts of OP-118 have been recovered in the urine. J Faropenem is a penem antibacterial that is given orally as the sodium salt for the treatment of susceptible infections. P..r�p(l_r?_li<>.n.� . Pharmacokinetics Faropenem medoxomil (USAN) (A-0026; Bay-56-6854; ProprietaryPreparations (details are given in Volume B) Ethionamide has been given as a sugar-coated tablet or SUN-A0026; SUN-208) has been investigated for the more recently as a more stable film-coated tablet. Both treatment of respiratory-tract infections and uncomplicated Single-ingredient Preparations. Canad.: Dificid; Denm.: Dificlir; formulations are readily absorbed from the gastrointestinal skin and skin-structure infections. NOTE. Faropenem Irl. : Dificlir; Norw.: Dificlir; Spain: Dificlir; Swed.: Difidir; UK: tract: after an oral dose of 2 50 mg, sugar-coated tablets medoxomil has also been referred to as faropenem daloxate Dificlir; USA: Dificid. produce a peak plasma concentration of about 1.5 micro­ although such use of the term daloxate is not in keeping grams/mL after 1.5 hours, while film-coated tablets give a with INN nomenclature conventions. (BAN, USAN, r/NN} peak plasma concentration of 2.16micrograms/mL after References. Fleroxacin about I hour. Distribution of ethionamide from the film­ 1. et al. Critchley IA, Activities of faropenem, an oral 13 -lactam, against �teroi:sastipj; Fl�roxa�lniJ; Flerox.adno; f!eroxoci· coated tablet into body tissues and fluids was expected to be recent US isolates of Streptococcus pneumoniae, Haemophilus ·. AM,8�3:n �o-23c6240/(:)QO; .\IlJJ�pOK!?al.!!o\K, similar to that of the sugar-coated tablets. Ethionamide from influenzae, and Moraxella catarrhalis. Antimicrob Agents Chemother \.lfll:.• -2}:6240; 2002; 46: 550-5. t 8·Di&;f!uoro-h(2·fluoroEO<thyll-1 4-dl!)ydro,7-(4-methylcl· \ . • sugar-coated tablets is widely distributed throughout body 2. von Eiff C, et a!. Comparative in vitro activity of faropenem against piper\ltit'lyl),4-oxe"3'quinoltnecarboxylic;ildd•. tissues and fluids. It crosses the placenta and penetrates the staphylococci. Antimicrob Chemother 2002; 50: 277-80. uninflamed meninges, appearing in the CSF in concentra­ 3. Milatovic D, et al. In vitro activity of faropenem against 5460 clinical J 50: C:tzflraF.al'!P-;=;$693 tions equivalent to those in serum. It is about 30% bound to bacterial isolates from Europe. Antimicrob Chemother 2002; 293-9. CAS ·;;.. 4. Wexler et a!. In vitro activities of faropenem against 579 strains of plasma proteins. The half-life for the sugar-coated tablet is , J 79660-'72-3. anaerobicHM bacteria. Antimicrob Agents Chemother 2002; 46: 3669-75. reported to be 2 to 3 hours and 1.92 hours for the film­ 5. Jones ME, eta!. Activity of faropenem, a new furanem, against European ATCC.:..JQ 1MA08. coated tablet. Ethionamide is extensively metabolised, respiratory pathogens collected during 2000-2001: a comparison with ATCYet - QJOIMA08. 51: � probably in the liver, to the active sulfoxide and other other beta-lactam agents.