Use of Sublingual Tacrolimus in Adults Undergoing Hematopoietic Cell Transplant: A Pilot Study

Abstract

The national shortage of oral (PO) and intravenous (IV) tacrolimus, as well as the undesirable sequelae of IV administration, call for innovative solutions to conserve existing supply and optimize safety and efficacy of medication delivery. Sublingual (SL) administration of tacrolimus is widely used as an alternative to the IV route in the solid organ transplant population and similar benefits may be appreciated by patients undergoing hematopoietic cell transplant (HCT). The most widely accepted SL:PO dose conversion ratio has been 0.5 based on available evidence. We sought to demonstrate feasibility of SL tacrolimus use and estimate a SL:PO conversion ratio in the HCT setting. Ten adults (median age 60.5 years) undergoing allogeneic HCT received tacrolimus 0.04 mg/kg/dose, based on ideal body weight, twice daily beginning 3 days prior to transplant. Initial doses were given via SL route and a steady state trough level was collected after 4 consecutive doses. Participants were then switched to tacrolimus PO, the dose was adjusted for a goal trough 8-12 ng/mL, and another steady state trough was drawn (Figure 1). Trough concentration was divided by total daily dose for each route to determine the dosing ratio of SL:PO (Table 1). Median trough level following SL administration was 11.3 ng/mL. Three of these were within goal, 3 were low (4.7-6.4 ng/mL) and 4 were elevated (15.9-18.6 ng/mL). Median SL:PO ratio was 0.99. In 5 patients the SL:PO ratio was Results demonstrate reliable absorption with SL tacrolimus use in patients undergoing HCT. This represents an alternative drug delivery method in patients with barriers to PO administration or in the setting of limited availability of the IV product. This preliminary experience identified an SL:PO ratio of 0.99 with some degree of variability. Fluctuating clinical status and changes in interacting medications are important to consider when adjusting doses or converting between routes and may influence this ratio. Further study is needed to better elucidate the a more precise SL:PO dose conversion ratio and understand the impact of various drug-drug interactions.