Captopril Azathioprine

A 47-year-old woman with multiple medical problems stabilised on warfarin (and also taking azathioprine, captopril, furosemide, insulin, capto-pril, prednisone, levothyroxine, valproic acid and zolpidem) had all her teeth removed under general anaesthetic. Sixteen days later she needed a dental abscess drained and was given oral clindamycin 300 mg four times daily with ibuprofen 600 mg for any discomfort. On day 17 she needed a suture to stop some bleeding and her INR was found to be 3.5. By day 20 she had developed more severe oral bleeding, which needed emergency room treatment. Her INR was found to have risen to 13 and her haemat-ocrit decreased to 18%. She was treated successfully with a blood transfusion and vitamin K. ... 

ACE INHIBITORS AZATHIOPRINE Risk of anaemia with captopril and enalapril and leukopenia with captopril The exact mechanism is uncertain. Azathioprine-induced impairment of haematopoiesis and ACE inhibitor-induced l in erythropoietin may cause additive effects. Enalapril has been used to treat post-renal transplant erythrocytosis Monitor blood counts regularly... 

Antiviral agents acyclovir, amantadine, azidofhymidine Diuretics furosemide, hydrochlorothiazide, efhacrynic acid ACE inhibitors captopril, enalapril, ramipril, delapril, quinapril Antineoplastics methotrexate, azathioprine, doxorubicin, 5-fluouracil Antiepileptics valproic acid (from Ref. [95])... 

These interaetions are not elearly established, and the reaction appears to he rare and unpredictable. All that can he constructively said is that patients taking both drugs should he very closely monitored for any signs of hypersensitivity (e.g. skin reactions) or low white cell count (sore throat, fever), especially if they have renal impairment. The UK manufacturer of captopril recommends that diffeiential white hlood cell counts should be performed before adding allopurinol, then every 2 weeks during the first 3 months of treatment, and periodically thereafter. Similar caution and advice is given by the UK manufacturers of several other ACE inhibitors. For other possible interactions with ACE inhihitors that might result in an increased risk of leucopenia see also ACE inhihitors + Azathioprine , p.l8 and ACE inhibitors + Procainamide , p.33. 

Anaemia has been seen in patients given azathioprine with enal-april or captopril. Leucopenia occasionally occurs when captopril is given with azathioprine. 

Anaemia caused by captopril and enalapril has been seen in kidney transplant patients and in dialysis patients (see ACE inhibitors and Angiotensin II receptor antagonists + Epoetin , p.25). The evidence that this effect can be potentiated by azathioprine is limited, but it would be prudent to monitor well if these drugs are used together. 

The evidence that the concurrent use of ACE inhibitors and azathioprine increases the risk of leucopenia is also limited. However, the UK manufacturer of captopril recommends that captopril should be used with extreme caution in patients receiving immunosuppressants, especially if there is renal impairment. They advise that in such patients differential white blood cell counts should be performed before starting captopril, then every 2 weeks in the first 3 months of treatment, and periodically thereafter. The UK manufacturers of a number of other ACE inhibitors also state in their prescribing information that the use of ACE inhibitors with cytostatic or immunosuppressive drugs may lead to an increased risk of leucopenia. For other potential interactions with ACE inhibitors that might lead to an increased risk of leucopenia, see also ACE inhibitors + Allop-urinoE, p.l3, and ACE inhibitors + Proeainamide , p.33. 

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