Evolving Role of Thiopurines in Inflammatory Bowel Disease in the Era of Biologics and New Small Molecules.

In recent years, with the increasing availability of biologic therapies and due to safety concerns, the role of thiopurines in the management of inflammatory bowel disease has been questioned. While acknowledging that the benefit/risk ratio of biologic therapies is very high, they are expensive and are not required by a majority of patients. Therefore, thiopurines do retain an important role as steroid-sparing and maintenance agents when used as monotherapy, and in combination therapy with biologics due to their clinical and pharmacokinetic optimization of anti-tumor necrosis factor agents in particular. Safety concerns with thiopurines are real but also relatively rare, and with careful pre-treatment screening and ongoing monitoring thiopurine benefits outweigh risks in the majority of appropriately selected patients. Measurement of newer pharmacogenomic markers such as nudix hydrolase 15 (NUDT15), when combined with knowledge of existing known mutations (e.g., thiopurine S-methyltransferase-TPMT), will hopefully minimize the risk of potentially life-threatening leukopenia by allowing for pre-treatment dosing stratification. Further optimization of thiopurine dosing via measurement of thiopurine metabolites should be performed routinely and is superior to weight-based dosing. The association of thiopurines with malignancies including lymphoproliferative disorders needs to be recognized in all patients and individualized in each patient. The decrease in lymphoma risk after thiopurine cessation provides an incentive for thiopurine de-escalation in appropriate patients after a period of prolonged deep remission. This review will summarize the current role of thiopurines in inflammatory bowel disease management and provide recommendations for commencing and monitoring therapy, and when to consider de-escalation.

Should sildenafil be available over the counter?

INTRODUCTION: This article considers the process of re-classification of prescription drugs from prescription-only medications to over-the-counter (OTC) prescription drugs. SOURCES OF DATA: The recent change in classification for emergency contraception and simvastatin is explored in detail with similarities and differences being considered for a similar argument to be made for sildenafil. AREAS OF AGREEMENT: The benefits for patients, physicians and other healthcare professionals are considered in detail. AREAS OF CONTROVERSY: We raise concerns about recently developed and existing patient group directions that, although extensive in their assessment, may omit to identify significant contributory factors which would necessitate appropriate medical intervention. GROWING POINTS: While the decision for re-classification to OTC would depend on a number of factors, we argue that, with the proviso of proper assessments being made, sildenafil should be made available as an OTC medication. AREAS TIMELY FOR DEVELOPING RESEARCH: The safety and use of OTC medications for erectile dysfunction at a time when many first line prescription agents are reaching generic status.