Bleeding interaction between fluconazole and warfarin: LANCE
A 71-year-old woman with paroxysmal atrial fibrillation being treated with warfarin 3·75 mg/day presented with a 5-day history of increasing swelling in her neck, sialorrhoea, and difficulty swallowing. 1 week earlier, she had been started on fluconazole 200 mg once a day because of oral candidiasis. She was afebrile.

Physical examination showed a large, soft, dark-red swelling on the floor of her mouth: her tongue was displaced superiorly. She had a sublingual haematoma (figure). Laboratory testing showed a C-reactive protein level of 65 mg/L (normal value <5·0 mg/L), a white cell count of 12·5 × 109 per L with 83·3% neutrophils, and a prothrombin time of less than 5% (normal value >70%) with an international normalised ratio (INR) of more than 9·0 (normal range 0·8–1·3).

A CT scan confirmed the presence of a retropharyngeal haematoma with marked stenosis of the oropharynx at the level of the epiglottis (figure). Coagulation was rapidly corrected with prothrombin complex concentrate and intravenous vitamin K, leading to spontaneous resolution of the haematoma over the course of 1 week while the patient was under close surveillance.

Airway evaluation and management are of paramount importance in such cases, and endotracheal intubation is indicated if the airway is severely compromised. Prophylactic antibiotics and steroids are sometimes proposed—although there is no definitive evidence to support their use. Spontaneous upper airway haematoma is rare.

Key takeaways:-
- In this case, warfarin overdose was the most likely cause mediated through interaction with fluconazole.

- Warfarin's primary metabolic pathway involves the cytochrome P450 2C9 isoform, and fluconazole is a strong inhibitor of this enzyme.

- Avoidance of fluconazole in patients on warfarin is advisable- unless the dose of warfarin is empirically reduced and the INR is closely monitored.

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32217-7/fulltext
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