Tetracyclines Coumarins

Penicillin, the first natural antibiotic produced by genus Penicillium, discovered in 1928 by Fleming, as well as sulfonamides, the first chemotherapeutic agents discovered in the 1930s, lead a long list of currently known antibiotics. Besides 3-lactams (penicillins and cephalosporines) and sulfonamides, the list includes aminoglycosides, macrolides, tetracyclines, quinolones, peptides, polyether ionophores, ri-famycins, linkosamides, coumarins, nitrofurans, nitro heterocytes, chloramphenicol, and others. 

Clinically important, potentially hazardous interactions with beta andrenergic blocking agents, chloramphenicol, cimetidine, dofibrate, coumarin deriveratives, disopyramide, MAO inhibitors, miconazole, phenylbutazone, salicylates, sulphonamides, tetracycline... 

A reduction in efficacy due to an interaction can sometimes be just as harmful as an increase patients taking warfarin who are given rifampicin need more warfarin to maintain adequate and protective anticoagulation (see Coumarins + Antibacterials Rifamycins , p.375), while patients taking tetracyclines , (p.347) or quinolones , (p.332) need to avoid antacids and milky foods (or separate their ingestion) because the effects of these antibacterials can be reduced or even abolished if admixture occurs in the gut. 

Isolated cases suggest that doxycycline and tetracycline can increase the effects of coumarins. Similarly, some small studies (none controlled) suggest that chlortetracycline (alone or with oxytetracycline), doxycycline, or the tetracyclines as a class may increase the risks of over-anticoagulation, but there appear to be no studies of the effect of tetracyclines on the pharmacokinetics of coumarins. However, the related antibacterial, tigecycline, increased the AUC of warfarin, and has been shown to increase the prothrombin time when given alone. 

There are no controlled studies of the effect of any tetracycline on the pharmacokinetics or pharmacodynamics of warfarin or other coumarins, although there are data for tigecycline, a new glycylcycline antibacterial structurally related to tetracyclines. 

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