Optimizing Thiopurine Therapy with a Xanthine Oxidase Inhibitor in Patients with Systemic Autoimmune Diseases: A Single-Centre Experience.

Background: Thiopurines are a mainstay of therapy for autoimmune diseases. However, up to 20% to 30% of patients experience overproduction of the methylated metabolites, known as 6-MMP, to the detriment of the active metabolite, 6-thioguanine nucleotide (6-TGN). These patients, commonly referred to as "shunters", are predisposed to thiopurine resistance and hepatotoxicity.

Clozapine intoxication with severe adverse effects induced by an inflammatory and infectious process: a case report.

Background: Clozapine intoxication can be life-threatening. Outside of the common drug-drug interactions, tobacco smoking, and caffeine consumption, infectious and inflammatory processes are important contributors to clozapine intoxication. Although this relationship has been reported previously, the literature is scant of proper research articles describing the presentation and management of this unpredictable interaction.

Clinical Importance of Monitoring Unbound Valproic Acid Concentration in Patients with Hypoalbuminemia.

Study Objective: Because the pharmacokinetic evaluation of valproic acid (VPA) based on total drug concentration may be misleading in patients with hypoalbuminemia as a result of saturable protein binding and saturable metabolism, we sought to investigate the usefulness of therapeutic drug monitoring of unbound VPA concentration in a real-world clinical context, with a focus on clinically significant neurologic adverse outcomes.

Design: Retrospective analysis.

Setting: Large academic tertiary care hospital in Montreal, Canada.

Metabolite monitoring to guide thiopurine therapy in systemic autoimmune diseases.

6-Thioguanine nucleotide (6-TGN) is the active metabolite of thiopurine drugs azathioprine and 6-mercaptopurine. 6-Methylmercaptopurine (6-MMP) is an inactive and potentially hepatotoxic metabolite. A subgroup of patients (shunters) preferentially produce 6-MMP instead of 6-TGN, therefore displaying thiopurine resistance and risk for hepatotoxicity.

Chronic Diarrhea Associated with High Teriflunomide Blood Concentration.

Objective: To report the case of a patient treated with leflunomide that presented with chronic diarrhea associated with high teriflunomide blood concentration. An 84-year-old woman taking leflunomide 20 mg once daily for the past 2 years to treat rheumatoid arthritis (RA) was investigated for severe chronic diarrhea that had been worsening for the past 5 months. The patient's general condition progressively deteriorated and included electrolyte imbalances and a transient loss of consciousness.

Interrater agreement for two systems used to determine the probability of heparin-induced thrombocytopenia.

Purpose: The interrater reliability of the 4T's method and the HIT expert probability (HEP) score for clinical evaluation of suspected heparin-induced thrombocytopenia (HIT) was investigated.

Methods: Patients hospitalized over a three-year period who were tested for HIT via anti-platelet factor 4 (anti-PF4) antigen assay were identified using laboratory data; 127 patient cases met the study inclusion criteria. Nine clinical pharmacists with expertise in HIT management evaluated the 127 cases using two pretest scoring systems: the 4T's score and the HEP score.

A metoprolol-terbinafine combination induced bradycardia.

To report a sinus bradycardia induced by metoprolol and terbinafine drug-drug interaction and its management. A 63 year-old Caucasian man on metoprolol 200 mg/day for stable coronary artery disease was prescribed a 90-day course of oral terbinafine 250 mg/day for onychomycosis. On the 49th day of terbinafine therapy, he was brought to the emergency room for a decrease of his global health status, confusion and falls.

Febuxostat as a novel option to optimize thiopurines' metabolism in patients with inadequate metabolite levels.

Objective: To report the use of febuxostat in order to potentiate thiopurines' metabolism in a patient on azathioprine (AZA) therapy with low metabolite 6-thioguanine nucleotides (6-TGN) levels and elevated metabolite 6-methylmercaptopurine (6-MMP) levels.

Case Summary: A 44-year-old woman with a history of anti-signal recognition particle necrotizing myopathy was treated with AZA-allopurinol combination therapy. When she developed an atypical drug-induced hypersensitivity syndrome, allopurinol was replaced by the new xanthine oxidase (XO) inhibitor febuxostat, at a daily dose of 40 mg.