The chemical structure of cefamandole, like that of several other cephalosporins, contains an N-methylthiotetrazole (NMTT or 1-MTT) side chain.

As the antibiotic is broken down in the body, it releases free NMTT, which can cause hypoprothrombinemia (likely due to inhibition of the enzyme vitamin K epoxide reductase) and a reaction with ethanol similar to that produced by disulfiram (Antabuse), due to inhibition of aldehyde dehydrogenase.

Vitamin K supplement is recommended during therapy, and consumption of ethanol and ethanol-containing substances is discouraged.

The following represents cefamandole MIC susceptibility data for a few medically significant microorganisms.

CO2 is generated during the normal constitution of cefamandole and ceftazidime, potentially resulting in an explosive-like reaction in syringes.