226 Antibacterials

Cefminox Sodium (pINNM) variable activity against Citrobacter spp., and Pseudomonas aer- Pharmacopoeias. In US. uginosa and Bacteroides fragilis are generally resistant. USP 31 (Cefonicid Sodium). A white to off-white solid. Freely Cefminox sódico; Cefminox Sodique; MT-141; Natrii Cefminox- soluble in water, in sodium chloride 0.9%, and in glucose 5%; um. Sodium 7-{2-[(S)-2-amino-2-carboxyethyl]thioacetamido}- Pharmacokinetics very slightly soluble in dehydrated alcohol; soluble in methyl al- 7-methoxy-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem- Cefodizime is given by injection as the sodium salt. Intramuscu- cohol. pH of a 5% solution in water is between 3.5 and 6.5. Store 4-carboxylate. lar injection of 1 g cefodizime produces peak plasma concentra- in airtight containers. tions of about 60 to 75 micrograms/mL at about 1 to 1.5 hours. Натрий Цефминокс Immediately after intravenous doses of 1 or 2 g cefodizime mean C16H20N7NaO7S3 = 541.6. peak plasma concentrations of 215 and 394 micrograms/mL, re- Adverse Effects and Precautions CAS — 75481-73-1 (cefminox). spectively, have been achieved. Cefodizime is about 80% bound As for Cefalotin Sodium, p.219. to plasma proteins and is widely distributed into body tissues and fluids. It crosses the placenta and small amounts have been de- Cefonicid contains a substituted N-methylthiotetrazole side- chain, a structure associated with hypoprothrombinaemia. O tected in breast milk. Plasma elimination is reported to be tripha- + H3 N H H3CO H sic with a terminal elimination half-life of about 4 hours. The S S - Effects on the blood. References. OOC N CH3 half-life is prolonged by renal impairment. H N S N The majority of a dose is excreted unchanged in the urine; up to 1. Riancho JA, et al. Life-threatening bleeding in a patient treated O N 80% of a dose has been recovered within 24 hours. Cefodizime with cefonicid. Ann Intern Med 1995; 123: 472–3. COOH N N is mainly excreted by glomerular filtration with some tubular se- cretion. Probenecid delays excretion. Cefodizime is removed by Effects on the liver. References. (cefminox) dialysis. 1. Famularo G, et al. Eosinophilic hepatitis associated with cefoni- Uses and Administration cid therapy. Ann Pharmacother 2001; 35: 1669–71. Pharmacopoeias. Jpn includes the heptahydrate. Cefodizime is a third-generation cephalosporin antibacterial Profile with uses similar to those of cefotaxime (p.229). Sodium content. Each g of cefonicid sodium contains about Cefminox sodium is a cephamycin antibacterial with properties Cefodizime is given as the disodium salt by intramuscular injec- 3.4 mmol of sodium. similar to those of cefoxitin (p.230) but with an N-methylthi- tion or intravenously by injection or infusion in the treatment of otetrazole side-chain like cefamandole (p.220). It is given intra- susceptible infections. Doses are expressed in terms of the equiv- Interactions venously as the sodium salt but doses are expressed in terms of alent amount of cefodizime; 1.08 g of cefodizime sodium is As for Cefamandole, p.221. cefminox; 1.04 g of cefminox sodium is equivalent to about 1 g equivalent to about 1 g of cefodizime. Adults are usually given 1 of cefminox. A usual dose is 2 to 4 g daily given in divided doses. to 2 g every 12 or 24 hours for lower respiratory-tract infections Antimicrobial Action and upper and lower urinary-tract infections. Doses up to 4 g dai- ◊ References. Cefonicid sodium has an antimicrobial action and pattern of re- ly may be given in severe infection. In women with uncomplicat- sistance similar to those of cefamandole (p.221), although it is 1. Watanabe S, Omoto S. Pharmacology of cefminox, a new bacte- ed lower urinary-tract infections a single dose of 1 to 2 g may be generally less active against Gram-positive cocci. ricidal cephamycin. Drugs Exp Clin Res 1990; 16: 461–7. sufficient. For gonorrhoea a single dose of 0.25 to 0.5 g may be 2. Soriano F, et al. Comparative susceptibility of cefminox and ce- given. Doses may need to be reduced in patients with renal im- foxitin to β-lactamases of Bacteroides spp. J Antimicrob Chem- pairment (see below). Pharmacokinetics other 1991; 28: 55–60. Cefonicid is given parenterally as the sodium salt. Peak plasma 3. Aguilar L, et al. Cefminox: correlation between in-vitro suscep- ◊ References. concentrations ranging from 67 to 126 micrograms/mL have tibility and pharmacokinetics and serum bactericidal activity in been achieved 1 to 2 hours after a 1-g intramuscular dose. Cefo- healthy volunteers. J Antimicrob Chemother 1994; 33: 91–101. 1. Finch RG, et al., eds. Cefodizime: a third generation cepha- nicid is more than 90% bound to plasma proteins. It has a plasma 4. Mayama T, et al. Postmarketing surveillance on side-effects of losporin with immunomodulating properties. J Antimicrob cefminox sodium (Meicelin). Int J Clin Pharmacol Ther 1995; Chemother 1990; 26 (suppl C): 1–134. half-life of about 4.5 hours, which is prolonged in patients with 33: 149–55. 2. Barradell LB, Brogden RN. Cefodizime: a review of its antibac- renal impairment. 5. Hoellman DB, et al. In vitro activities of cefminox against anaer- terial activity, pharmacokinetic properties and therapeutic use. obic bacteria compared with those of nine other compounds. An- Drugs 1992; 44: 800–834. Therapeutic concentrations of cefonicid have been reported in a timicrob Agents Chemother 1998; 42: 495–501. 3. Thalhammer F, et al. Single-dose cefodizime as infection proph- wide range of body tissues and fluids. 6. Torres AJ, et al. Cefminox versus metronidazole plus gentamicin ylaxis in abdominal surgery: a prospective multicenter study. In- in intra-abdominal infections: a prospective randomized control- fection 1998; 26: 136–8. Up to 99% of a dose of cefonicid is excreted unchanged in the led clinical trial. Infection 2000; 28: 318–22. 4. Matsumoto T, et al. Single dose of cefodizime completely erad- urine within 24 hours. Probenecid reduces excretion of cefoni- icated multidrug-resistant strain of Neisseria gonorrhoeae in ure- cid. Sodium content. Each g of cefminox sodium contains about thritis and uterine cervicitis. J Infect Chemother 2006; 12: 97–9. 1.84 mmol of sodium. 5. Matsumoto T, et al. Multiple doses of cefodizime are necessary Uses and Administration Preparations for the treatment of Neisseria gonorrhoeae pharyngeal infection. J Infect Chemother 2006; 12: 145–7. Cefonicid is a second-generation cephalosporin antibacterial Proprietary Preparations (details are given in Part 3) used similarly to cefamandole (p.221) in the treatment of suscep- Jpn: Meicelin; Port.: Te n c ef ; Spain: Tencef; Thai.: Meicelin. Administration in renal impairment. Doses of cefodizime tible infections and for surgical infection prophylaxis. should be reduced in patients with renal impairment according to creatinine clearance (CC): It is given as the sodium salt by deep intramuscular injection, or • CC 10 to 30 mL/minute: 1 to 2 g daily intravenously by slow injection over 3 to 5 minutes or by infu- Cefodizime Sodium (BANM, rINNM) sion. Doses are expressed in terms of the equivalent amount of • CC less than 10 mL/minute: 0.5 to 1 g daily Cefodizima sódica; Céfodizime Sodique; HR-221; Natrii Cefodiz- cefonicid; 1.08 g of cefonicid sodium is equivalent to about 1 g imum; S-771221B; Sefodizim Disodyum; THR-221; TRH-221. In patients undergoing dialysis, 0.5 to 1 g daily is given after di- of cefonicid. The usual dose is cefonicid 1 g once daily. For un- (Z)-7-[2-(2-Aminothiazol-4-yl)-2-methoxyiminoacetamido]-3- alysis. complicated urinary-tract infections, a dose of 500 mg once daily (5-carboxymethyl-4-methylthiazol-2-ylthiomethyl)-3-cephem-4- is recommended; up to 2 g once daily has been given in severe Preparations infections. More than 1 g should not be injected intramuscularly carboxylic acid, disodium salt. Proprietary Preparations (details are given in Part 3) into a single site. Натрий Цефодизим Austria: Timecef; Ital.: Diezime; Modivid; Timecef; Jpn: Kenicef; Mex.: Modivid†; NZ: Timecef; Port.: Modivid; Turk.: Modivid. For surgical infection prophylaxis, a single dose of 1 g given 1 C20H18N6Na2O7S4 = 628.6. CAS — 69739-16-8 (cefodizime); 86329-79-5 (cefodiz- hour before surgical incision is usually sufficient, but may be ime sodium). given daily for a further 2 days in prosthetic arthroplasty or open- ATC — J01DD09. heart surgery. Cefonicid Sodium (BANM, USAN, rINNM) ATC Vet — QJ01DD09. Cefonicid sódico; Cefonicide sodique; Céfonicide Sodique; Cefo- ◊ References. nicidum natricum; Natrii Cefonicidum; SKF-D-75073-Z ; SKF-D- 2 1. Saltiel E, Brogden RN. Cefonicid: a review of its antibacterial H3C 75073-Z (cefonicid monosodium). 7-[(R)-Mandelamido]-3-(1- activity, pharmacological properties and therapeutic use. Drugs O O HH sulphomethyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carbox- 1986; 32: 222–59. N S ylic acid, disodium salt. N H Натрий Цефоницид Administration in renal impairment. For patients with re- N S S nal impairment a loading dose equivalent to cefonicid 7.5 mg/kg N COOH O C18H16N6Na2O8S3 = 586.5. is recommended, followed by reduced maintenance doses ac- S COOH N CAS — 61270-58-4 (cefonicid); 61270-78-8 (cefonicid cording to the creatinine clearance and the severity of the infec- CH NH2 3 disodium); 71420-79-6 (cefonicid monosodium). tion. A dose supplement is not required after dialysis. ATC — J01DC06. (cefodizime) ATC Vet — QJ01DC06. Preparations

Pharmacopoeias. In Jpn. USP 31: Cefonicid for Injection.

Adverse Effects and Precautions O Proprietary Preparations (details are given in Part 3) As for Cefotaxime, p.228. HH S HO3S Belg.: Monocid†; Israel: Monocef; Ital.: Abiocef†; Auricid†; Bacid†; Biocil; Sodium content. Each g of cefodizime sodium contains about N Bioticic; Cefobacter; Cefodie; Cefoger†; Cefok; Cefoplus; Cefosporin†; 3.2 mmol of sodium. H Chefir; Clastidin†; Daycef; Delsacid†; Diespor; Emidoxin; Epicef†; Fonexel†; OH N S N Fonicef†; Fonicid; Fonisal†; Framecef; Ipacid†; Krucef; Lampocef†; Lisa; Max- Interactions O N id; Microcid†; Modicef; Modiem; Monobios; Monobiotic; Monocid†; Necid; Probenecid reduces the renal clearance of cefodizime. Nokid; Pantacid†; Parecid; Praticef; Raikocef; Renbiocid†; Rocid†; Silvercef†; COOH N N Sintocef; Sofarcid; Unicid†; Valecid; Port.: Monocid; Spain: Monocid; Uni- Antimicrobial Action die; USA: Monocid†. Cefodizime has similar antimicrobial activity to that of cefotaxi- (cefonicid) me (p.228) although cefodizime has no active metabolite. It has