ance; exogenous consumption of vitamin K by changes in diet, multivitamin supplementation, or nutritional products; and drugs that interfere with warfarin's effect ...
Case Reports
alors qu’elle recevait toujours du topiramate, qu’elle ne nécessitait plus d’hospitalisations, ce qui est toujours le cas au moment de la rédaction de cette histoire de cas. DISCUSSION: Ce cas vient illustrer le fait que le topiramate, tel que rapporté précédemment dans la littérature, peut être un outil pharmacologique utile pour traiter des troubles affectifs et aussi induire une perte de poids chez une population de patients chez lesquels la surcharge pondérale est un problème fréquent. La patiente dont le cas est discuté ici, ne présentait aucunes maladies aiguës ni aucuns changements récents dans son état de santé, sa diète ou sa médication, changements qui
auraient pu expliquer la perte pondérale soudaine. De plus, le comportement de la patiente ne s’était pas amélioré sous un traitement optimal par l’association d’acide valproïque, de citalopram, et de chlorpromazine jusqu’à l’addition du topiramate comme thérapie adjuvante. CONCLUSIONS: Des études contrôlées sont nécessaires pour évaluer l’emploi du topiramate chez une population de patients psychiatriques, et en particulier, pour évaluer les bénéfices lors d’obésité concomitante. Denyse Demers
Warfarin Resistance Due to Sulfasalazine Anna M Teefy, Janet E Martin, and Michael J Kovacs
OBJECTIVE:
To report a case of warfarin resistance associated with the use of sulfasalazine.
CASE SUMMARY: A 37-year-old white woman on oral anticoagulant therapy with warfarin was being evaluated for complaints of joint pains. Her past medical history consisted of recurrent deep-vein thrombosis, asthma, and ulcerative colitis. Warfarin concentrations had consistently remained within the therapeutic range with dosages of approximately 30 mg per week. In an attempt to treat arthritis, her gastroenterologist replaced 5-aminosalicylic acid (5-ASA) with sulfasalazine 1000 mg four times daily. Subsequent to the medication changes, the international normalized ratio (INR) decreased and remained at subtherapeutic concentrations despite increases in the warfarin dosage. During this period, the patient developed a deep-vein thrombosis in the right popliteal vein. The INR did not return to an acceptable level until six weeks after sulfasalazine was started. The new warfarin dosage was 75 mg per week, a 250% dosage increase. When sulfasalazine was discontinued and 5-ASA reinstituted, the warfarin dosage requirements to achieve therapeutic INRs returned to weekly dosages of approximately 45 mg. DISCUSSION:
Sulfonamides have been well documented to enhance the anticoagulant effect of warfarin. This patient developed a new deep-vein thrombosis due to failure in maintaining therapeutic INR levels after the recent introduction of sulfasalazine. We suspect that she developed warfarin resistance secondary to concomitant use of sulfasalazine. This patient demonstrated warfarin resistance as opposed to enhanced anticoagulant effect with sulfasalazine.
CONCLUSIONS:
Clinicians managing warfarin therapy should exercise caution when sulfasalazine is added to a patient’s medical regimen. This case suggests a possible warfarin–sulfasalazine interaction that resulted in warfarin resistance.
KEY WORDS: sulfasalazine, warfarin.
Ann Pharmacother 2000;34:1265-8.
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arfarin is a commonly used oral anticoagulant, due W to its bioavailability and good pharmacokinetics. Warfarin is rapidly and completely absorbed and then is highly bound to plasma proteins, in particular, albumin. Warfarin is metabolized by hepatic microsomal enzymes, and inactive metabolites are excreted in the urine.2 A decreased anticoagulant effect from warfarin can be determined by examining causes for acquired or hereditary warfarin resistance. Acquired warfarin resistance is defined as achieving subtherapeutic responses with dosages
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highly exceeding amounts previously prescribed.3 Acquired warfarin resistance can be attributed to patient noncompliance; exogenous consumption of vitamin K by changes in diet, multivitamin supplementation, or nutritional products; and drugs that interfere with warfarin’s effect by decreasing its absorption or increasing its clearance. Many drug interactions have been associated with warfarin that may enhance or inhibit the anticoagulant effects.4 There is more documentation4,5 of drugs enhancing rather than inhibiting warfarin’s effect. Warfarin resistance is rarely due to impaired absorption unless the patient has abnormalities in the gastrointestinal tract (e.g., short bowel syndrome, irritable bowel disease).3,6 Herbal preparations and alcohol have
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also been implicated in interfering with response to warfarin therapy. Laboratory error is another factor to be considered when the monitoring values differ from those that have been stabilized. Hereditary warfarin resistance is thought to be due to the presence of abnormal enzymes or defective receptors. These enzymes or receptors either have an increased affinity for vitamin K or decreased affinity for warfarin. Hereditary warfarin resistance has been reported in only four cases.3,6 Sulfasalazine is classified as a sulfonamide. It is poorly absorbed;
