Cefamandole Sodium

(BANM, rINNM)
Synonyms: Cefamandol sódico; Céfamandole Sodique; Cephamandole Sodium; Natrii Cefamandolum.
Cyrillic synonym: Натрий Цефамандол.

💊 Chemical information

Chemical formula: C18H17N6NaO5S2 = 484.5.
CAS — 30034-03-8.
ATC — J01DC03.
ATC Vet — QJ01DC03.

💊 Adverse Effects and Precautions

As for Cefalotin Sodium. As mentioned under Cefalotin, cephalosporins with an N-methylthiotetrazole side-chain such as cefamandole (and possibly those with methylthiadiazolethiol or Nmethylthiotriazine side-chains as well) may produce bleeding disorders associated with hypoprothrombinaemia and/or platelet disorders.

Sodium content.

1.05 g of cefamandole sodium and 1.11g of cefamandole nafate each contain about 2.2 mmol of sodium.

💊 Interactions

A disulfiram-like interaction with alcohol may occur and has been attributed to the N-methylthiotetrazole side-chain of cefamandole; patients should avoid alcohol during, and for at least several days after, cefamandole treatment. Interactions are also possible with preparations containing significant amounts of alcohol. Cefamandole, and other cephalosporins with an Nmethylthiotetrazole side-chain, may enhance the hypoprothrombinaemic response to anticoagulants as discussed under Warfarin. Probenecid reduces the renal clearance of cefamandole and many other cephalosporins.
1. Portier H, et al. Interaction between cephalosporins and alcohol. Lancet 1980; ii: 263
2. Drummer S, et al. Antabuse-like effect of β-lactam antibiotics. N Engl J Med 1980; 303: 1417–18.

💊 Antimicrobial Action

Cefamandole is bactericidal and acts similarly to cefalotin, but has a broader spectrum of activity. It generally has similar or less activity against Gram-positive staphylococci and streptococci, but is resistant to some beta-lactamases produced by Gram-negative bacteria. It is more active than cefalotin against many of the Enterobacteriaceae including some strains of Enterobacter, Escherichia coli, Klebsiella, Salmonella, and some Proteus spp. However, resistance to cefamandole and other beta lactams has emerged in some species, notably Enterobacter, during treatment with cefamandole. Cefamandole is very active in vitro against Haemophilus influenzae although an inoculum effect has been reported for beta-lactamase-producing strains.
Like cefalotin, most strains of Bacteroides fragilis are resistant to cefamandole, as are Pseudomonas spp.
1. Sabath LD. Reappraisal of the antistaphylococcal activities of first-generation (narrow-spectrum) and second-generation (expanded-spectrum) cephalosporins. Antimicrob Agents Chemother 1989; 33: 407–11.

💊 Pharmacokinetics

Cefamandole is poorly absorbed from the gastrointestinal tract. It is given intramuscularly or intravenously, usually as the nafate which is rapidly hydrolysed to release cefamandole in vivo. Peak plasma concentrations for cefamandole of about 13 and 25 micrograms/mL have been achieved 0.5 to 2 hours after intramuscular doses of 0.5 and 1 g respectively; concentrations are very low after 6 hours. About 70% is bound to plasma proteins. The plasma half-life varies from about 0.5 to 1.2 hours depending on the route of injection; it is prolonged in patients with renal impairment. Cefamandole is widely distributed in body tissues and fluids including bone, joint fluid, and pleural fluid; it diffuses into the CSF when the meninges are inflamed, but concentrations are unpredictable. Cefamandole has also been detected in breast milk. It is rapidly excreted unchanged by glomerular filtration and renal tubular secretion; about 80% of a dose is excreted within 6 hours and high urinary concentrations are achieved. Probenecid competes for renal tubular secretion with cefamandole resulting in higher and prolonged plasma concentrations of cefamandole. Therapeutic concentrations of cefamandole are achieved in bile. Cefamandole is removed by haemodialysis to some extent.

💊 Uses and Administration

Cefamandole is a second-generation cephalosporin antibacterial used in the treatment of infections due to susceptible bacteria and for surgical infection prophylaxis. It is given principally as cefamandole nafate (the sodium salt of cefamandole formyl ester). Doses are expressed in terms of the equivalent amount of cefamandole; 1.05 g of cefamandole sodium and 1.11 g of cefamandole nafate are each equivalent to about 1 g of cefamandole. It is given by deep intramuscular injection, by slow intravenous injection over 3 to 5 minutes, or by intermittent or continuous infusion in doses of 0.5 to 2 g every 4 to 8 hours for adults depending on the severity of the infection. Children over 1 month of age may be given 50 to 100 mg/kg daily in equally divided doses; 150 mg/kg daily may be given in severe infections, but this dose should not be exceeded. For details of reduced doses in patients with renal impairment, see below. If cefamandole is used with an aminoglycoside, the drugs should be given separately. For surgical infection prophylaxis, a dose of 1 or 2 g intravenously or intramuscularly 30 to 60 minutes before surgical incision, followed by 1 or 2 g every 6 hours for 24 to 48 hours, is recommended. For patients undergoing procedures involving implantation of prosthetic devices, cefamandole should be continued for up to 72 hours. Children over 3 months of age may be treated similarly to adults and given 50 to 100 mg/kg daily in equally divided doses.

Administration in renal impairment.

Doses of cefamandole should be reduced for patients with renal impairment. After an initial dose of 1 to 2 g the following maintenance doses have been recommended based on creatinine clearance (CC):
CC 50 to 80 mL/minute: 0.75 to 2 g every 6 hours
CC 25 to 50 mL/minute: 0.75 to 2 g every 8 hours
CC 10 to 25 mL/minute: 0.5 to 1.25 g every 8 hours
CC 2 to 10 mL/minute: 0.5 to 1 g every 12 hours
CC less than 2 mL/minute: 0.25 to 0.75 g every 12 hours

💊 Preparations

USP 31: Cefamandole Nafate for Injection.

Proprietary Preparations

Austral.: Mandol; Austria: Mandokef; Belg.: Mandol; Cz.: Mandol†; Gr.: Acemycin; Cefadin; Mandokef; Hong Kong: Mandol†; Hung.: Cefam; Mandokef†; Indon.: Dardokef; Dofacef; Irl.: Kefadol†; Ital.: Cefam; Cemado; Lampomandol; Mancef; Mandokef†; Mandolsan†; Septomandolo†; Neth.: Mandol; NZ: Mandol; Pol.: Tarcefandol; Port.: Mandokef†; Rus.: Cefat (Цефат); Mandol (Мандол); S.Afr.: Kefdole†; Mandokef; Switz.: Mandokef; Thai.: Cefadol; Cefmandol; Mandol†.
Published December 21, 2018.