Warfarin Doxycycline

There has been a report of bleeding and prolonged international normalized ratio in a 69-year-old man given warfarin and doxycycline (21). 

Baciewicz AM, Bal BS. Bleeding associated with doxycycline and warfarin treatment. Arch Intern Med 2001 161(9) 1231. 

Increased levels with amiodarone. sulfonamides, isoniazid, fluconazole. Unpredictable effetts with VPA and PB, Decreased effectiveness of warfarin, CBZ, doxycycline, estrogens. 

A 46-year-old woman is prescribed doxycycline for a diagnosis of community-acquired pneumonia. Her PMH is significant for iron-deficiency anemia, peptic ulcer disease, HTN, a recent DVT, and headaches. Her current medications include ferrous sulfate, ibuprofen, enalapril, acetaminophen, famotidine, and warfarin. Which of her following medications is most likely to result in decreased levels of doxycycline ... 

Clinically important, potentially hazardous interactions with aspirin, ciprofloxacin, doxycycline, hypoglycemics, lomefloxacin, lymecycline, methotrexate, minocycline, tetracycline, warfarin... 

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. 

Carbamazepine levels are increased by CYP3A4 inhibitors (cimetidine, macrolides, diltiazem, fluoxetine, ketoconazole, verapamil, valproate) levels are decreased by CYP3A4 inducers (cisplatin, doxorubicin, felbamate, phenobarbital, phenytoin, primidone, rifampin, theophylline). Carbamazepine may increase levels of clomipramine, phenytoin, and primidone and lithium toxicity may decrease levels of phenytoin, warfarin, oral contraceptives, doxycycline, theophylline, haloperidol, alprazolam, clozapine, ethosuximide, and valproate may interfere with other anticonvulsants. 

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