Aprepitant for the Treatment of Chronic Refractory Pruritus

Abstract

Chronic pruritus is a difficult condition to treat and is associated with several comorbidities, including insomnia, depression, and decreased quality of life. Treatment for chronic itch includes corticosteroids, antihistamines, and systemic therapies such as naltrexone, gabapentin, UV light therapy, and immunomodulatory treatments, including azathioprine, methotrexate, and cellcept. However, some patients still remain refractory to conventional therapy. Aprepitant is a neurokinin-1 receptor antagonist approved for the prevention of chemotherapy-induced and postoperative nausea and vomiting (CINV, PONV). Recently, aprepitant has demonstrated effectiveness in several case series and open label trials in relieving pruritus for patients refractory to other treatments. Patients with pruritus associated with Sézary syndrome, mycosis fungoides, lung adenocarcinoma, breast carcinoma, sarcomas, metastatic solid tumors, chronic kidney disease, hyperuricemia, iron deficiency, brachioradial pruritus, and Hodgkin's lymphoma have experienced considerable symptom relief with short-term use of aprepitant (up to two weeks). Due to differences in reporting and evaluation of drug effects, the mechanism of aprepitant's role is difficult to understand based on the current literature. Herein, we evaluate aprepitant's antipruritic effects and discuss its mechanism of action and adverse effects. We propose that aprepitant is an alternative for patients suffering from pruritus who do not obtain enough symptom relief from conventional therapy.

A patient with concurrent prurigo nodularis and squamous cell carcinomas of keratoacanthoma type: The role of aprepitant in diagnostic clarity

“…1 Because our patient did not respond to multiple first-and second-line therapies, the NK1 receptor antagonist, aprepitant, was trialed, as evidence suggested an improvement in pruritus severity in patients with PN and pruritus secondary to cutaneous T-cell lymphoma, solid tumors, antitumoral immunotherapies. 1,2,6 Recently, dupilumab, a monoclonal antibody directed against the interleukin receptor, was found to improve generalized PN; however, cost and administrative burdens may limit the accessibility of dupilumab in PN. 7 Although aprepitant was used off label for pruritus in this case, the low overall dose (80 mg 3 4 days) and infrequent dosing (every 3 months) made this an affordable option in this patient with refractory pruritus and PN.…”

“…Although no one causative chemical mediator of itch has been identified, substance P is thought to be a major contributor to the neurocutaneous transmission of pruritus. 2 By acting through the neurokinin-1 (NK1) receptor on epidermal dendritic cells, dermal fibroblasts, mast cells, and keratinocytes, substance P plays a role in neurogenic inflammation, pain, and pruritus. 2 In addition to its action at NK1 receptors, recent mouse studies suggest that substance P may also act via Mas-related Gproteinecoupled receptors (Mrgprs) on mast cells and dorsal root ganglia neurons to mediate neurogenic itch.…”

“…2 By acting through the neurokinin-1 (NK1) receptor on epidermal dendritic cells, dermal fibroblasts, mast cells, and keratinocytes, substance P plays a role in neurogenic inflammation, pain, and pruritus. 2 In addition to its action at NK1 receptors, recent mouse studies suggest that substance P may also act via Mas-related Gproteinecoupled receptors (Mrgprs) on mast cells and dorsal root ganglia neurons to mediate neurogenic itch. 3,4 The NK1 receptor antagonists inhibit substance Pemediated neurogenic inflammation by blocking both NK1 receptors and Mrgprs and have demonstrated variable efficacy in the treatment of pruritus and PN.…”

“…3,4 The NK1 receptor antagonists inhibit substance Pemediated neurogenic inflammation by blocking both NK1 receptors and Mrgprs and have demonstrated variable efficacy in the treatment of pruritus and PN. 2,3,5 Here we present a case of an immunocompromised patient with multiple prior NMSCs and multiple treatment-refractory PN successfully treated with the NK1 receptor antagonist aprepitant.…”

Treatment of Brachioradial Pruritus: A Systematic Review

“…46,47 Aprepitant, an NK-1 receptor antagonist originally approved for the prevention of chemotherapy-induced nausea and vomiting, has also been reported to be effective in chronic pruritides. 30,48 Anecdotal evidence demonstrates effect in BRP, however more studies are needed to support this medication. 30 Invasive treatment is appropriate when there is clear cervical pathology for BRP.…”