aprepitant and Pruritus

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.

Topics: Antiemetics; Aprepitant; Chronic Disease; Humans; Morpholines; Neurokinin-1 Receptor Antagonists; Pruritus; Quality of Life

Aprepitant is an FDA-approved medication for chemotherapy-induced nausea and vomiting. It blocks substance P binding to neurokinin-1; substance P has been implicated in itch pathways both as a local and global mediator.. We report a series of four patients, diagnosed with cutaneous T-cell lymphoma, who experienced full body pruritus recalcitrant to standard therapies. All patients experienced rapid symptom improvement (within days) following aprepitant treatment.. Aprepitant has been shown in small studies to be efficacious for treating chronic and malignancy-associated pruritus. Prior studies have shown no change in clinical efficacy of chemotherapeutics with concurrent aprepitant administration. These cases further demonstrate that aprepitant can be considered as a therapeutic option in malignancy-associated pruritus and further support the need for larger clinical trials.

Topics: Adult; Aged; Aprepitant; Female; Humans; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Morpholines; Neurokinin-1 Receptor Antagonists; Protein Binding; Pruritus; Substance P

Itch is a global clinical problem and finding effective treatment remains a therapeutic challenge because of the complex pathophysiology of itch. The key component of treating itch should be directed at the underlying etiologies when possible. However, without eradication of the underlying diseases, treatment is often palliative at best. Treatment with systemic therapies can vary according to the etiology of the chronic itch. The aim of this article is to review the major systemic anti-itch agents and give a summary on the possible systemic treatments for different types of itch.

Topics: Amines; Analgesics; Analgesics, Opioid; Anion Exchange Resins; Antidepressive Agents; Aprepitant; Cholagogues and Choleretics; Cholestasis; Cholestyramine Resin; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; Histamine Antagonists; Humans; Morpholines; Narcotic Antagonists; Neurokinin-1 Receptor Antagonists; Paraneoplastic Syndromes; Peripheral Nervous System Diseases; Pregabalin; Pruritus; Receptors, Opioid, kappa; Receptors, Opioid, mu; Rifampin; Thalidomide; Uremia; Ursodeoxycholic Acid

Patients with atopic dermatitis (AD) suffer from chronic inflammatory dermatitis and antihistamine-resistant itch. The management of intractable pruritus in AD is important, requiring the development of new therapeutic approaches. At present, the standard treatments for AD include topical anti-inflammatory drugs such as calcineurin inhibitors and corticosteroids. Topical emollient treatment is recommended to moisten the skin and to restore and maintain barrier function. Phototherapy is also effective in reducing the number of epidermal nerve fibers, normalizing imbalances in the levels of expression of axon guidance molecules, and inhibiting pruritus. Systemic treatments such as cyclosporine A and aprepitant are used to treat severe and intractable pruritus in AD. Clinical trials of dupilumab and CIM331 have displayed a significant reduction of pruritus in patients with AD. New antipruritic approaches are targeted to the central nervous system such as spinal interneurons and glial cells. This chapter describes therapeutic approaches for attenuating intractable itch in AD.

Topics: Administration, Cutaneous; Adrenal Cortex Hormones; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Aprepitant; Calcineurin Inhibitors; Cyclosporine; Dermatitis, Atopic; Dermatologic Agents; Emollients; Humans; Morpholines; Neurokinin-1 Receptor Antagonists; Phototherapy; Pruritus

Paraneoplastic itch occurs as the result of a systemic reaction to an underlying malignancy. Paraneoplastic itch is most commonly associated with lymphoproliferative malignancies and solid tumors that result in cholestasis. Paraneoplastic itch may occur in the absence of a primary rash or in association with dermatologic conditions such as erythroderma, acanthosis nigricans, dermatomyositis, Grover's disease, and eruptive seborrheic keratosis. Treatment of paraneoplastic itch is centered on targeting the underlying malignancy responsible for the systemic reaction. In cases of malignancy that are refractive to treatment, other therapies have been found to be effective for paraneoplastic itch, including selective serotonin reuptake inhibitors, mirtazapine, gabapentin, thalidomide, opioids, aprepitant, and histone deacetylase inhibitors.

Topics: Acantholysis; Acanthosis Nigricans; Analgesics, Opioid; Anticonvulsants; Antidepressive Agents; Aprepitant; Dermatitis, Exfoliative; Dermatomyositis; Histone Deacetylase Inhibitors; Humans; Ichthyosis; Immunosuppressive Agents; Keratosis, Seborrheic; Mianserin; Mirtazapine; Morpholines; Neoplasms; Neurokinin-1 Receptor Antagonists; Paraneoplastic Syndromes; Pruritus; Selective Serotonin Reuptake Inhibitors; Thalidomide

Substance P (SP) is an important mediator of pro-inflammatory mechanisms in the skin. It targets multiple cells such as keratinocytes, mast cells, and fibroblasts which are involved in the cutaneous generation of pruritus. This suggests that SP is an interesting target for therapy. In fact, in recent case reports and case series, SP antagonists demonstrated a significant antipruritic effect in acute and chronic pruritus such as drug-induced pruritus, paraneoplastic pruritus, prurigo nodularis, cutaneous T-cell lymphoma, and brachioradial pruritus.

Topics: Animals; Aprepitant; Humans; Morpholines; Pruritus; Receptors, Neurokinin-1; Substance P

Pruritus is one of the most common and challenging side effects of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and has impaired patients' quality of life and treatment compliance. Our study evaluated the efficacy and safety of aprepitant in managing EGFR-TKIs-related pruritus.. This randomized, double-blind, placebo-controlled study was conducted between December 2016 and August 2020 in China. Patients were eligible if they were 18 years or older and had histologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) with first onset of moderate to severe pruritus during EGFR-TKI treatment.. A total of 130 eligible patients were randomly assigned to aprepitant (n = 65) or desloratadine (n = 65) groups. The median (interquartile range [Q1, Q3]) age was 63 (54, 70) years, and 79 (60.8%) were women. Mean visual analog scale scores at baseline were 6.35 (95% confidence interval [CI], 5.89-6.82) in the aprepitant group and 5.94 (95% CI, 5.56-6.32) in the desloratadine group. After 1 week of treatment, 33 (53.2%) patients responded to aprepitant, which was significantly higher than that of 14 (23.7%) patients responded to desloratadine (p = .001). Moreover, patients in the aprepitant group had a significantly shorter response time than patients in the desloratadine group (mean [days], 13.39 [95% CI, 11.08-15.70] vs. 16.67 [95% CI, 14.19-19.13], p = .04). The most frequent drug-related adverse events in aprepitant group and desloratadine were constipation and dry mouth, and all adverse events were grade 1-2.. To the authors' knowledge, this is the first study to prospectively present that aprepitant elicited a better and faster response and mild toxicity for managing EGFR-TKI induced pruritus than desloratadine.. ClinicalTrials.gov Identifier: NCT02646020.

Topics: Aged; Aprepitant; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Female; Humans; Lung Neoplasms; Male; Middle Aged; Protein Kinase Inhibitors; Pruritus; Quality of Life

Aquagenic pruritus (AP), an intense sensation of scratching induced after water contact, is the most troublesome aspect of BCR-ABL1-negative myeloproliferative neoplasms (MPNs). Mostly described in polycythemia vera (PV, ~ 40%), it is also present in essential thrombocythemia (ET) and primary myelofibrosis (PMF) (10%). Even if this symptom can decrease or disappear under cytoreductive treatments, 30% of treated MPN patients still persist with a real impact on the quality of life (QoL). Because its pathophysiology is poorly understood, efficient symptomatic treatments of AP are missing. The neuropeptide substance P (SP) plays a crucial role in the induction of pruritus. Several studies showed the efficacy of aprepitant, an antagonist of SP receptor (NK-1R), in the treatment of chronic pruritus but never evaluated in AP. The objectives of APHYPAP are twofold: a clinical aim with the evaluation of the efficacy of two drugs in the treatment of a persistent AP for MPN patients and a biological aim to find clues to elucidate AP pathophysiology.. A multicentric, double-blind, double-placebo, randomized study will include 80 patients with MPN (PV or ET or PMF) treated since at least 6 months for their hemopathy but suffering from a persistent AP (VAS intensity ≥6/10). Patients will be randomized between aprepitant (80 mg daily) + placebo to match to hydroxyzine OR hydroxyzine (25 mg daily) + placebo to match to aprepitant for 14 days. At D0, baseline information will be collected and drugs dispense. Outcome measures will be assessed at D15, D30, D45, and D60. The primary study endpoint will be the reduction of pruritus intensity below (or equal) at 3/10 on VAS at D15. Secondary outcome measures will include the number of patients with a reduction or cessation of AP at D15 or D60; evaluation of QoL and AP characteristics at D0, D15, D30, D45, and D60 with MPN-SAF and AP questionnaires, respectively; modification of plasmatic concentrations of cytokines and neuropeptides at D0, D15, D30, and D60; and modification of epidermal innervation density and pruriceptor expression at D0 and D15.. The APHYPAP trial will examine the efficacy of aprepitant vs hydroxyzine (reference treatment for AP) to treat persistent AP in MPN patients. The primary objective is to demonstrate the superiority of aprepitant vs hydroxyzine to treat persistent AP of MPN patients. The treatment received will be considered efficient if the AP intensity will be reduced at 3/10 or below on VAS after 14 days of treatment. The results of this study may provide a new treatment option for this troublesome symptom and also give us more insights in the pathophysiology understanding of AP.. APHYPAP. NCT03808805 , first posted: January 18, 2019; last update posted: June 10, 2021. EudraCT 2018-090426-66.

Topics: Aprepitant; Cytoreduction Surgical Procedures; Humans; Hydroxyzine; Neoplasms; Pruritus; Quality of Life

Substance P (SP) and its receptor neurokinin 1 (NK1R) are thought to be involved in the pathogenesis of chronic prurigo. Here, we assessed SP serum levels, cutaneous NK1R expression, and the effects of topical aprepitant, an NK1R antagonist, in patients with chronic prurigo. SP and NK1R were increased, compared with controls, in the serum and in lesional vs. non-lesional skin of the patients, respectively. Aprepitant, in a randomized, placebo-controlled, split-sided, doubleblind trial, reduced the intensity of pruritus as assessed by visual analogue scale by >50% from baseline to day 28 (-35.2), but so did placebo vehicle (-38.1, p= 0.76). Overall clinical scores improved significantly by day 28 in both treatment groups, with no significant difference between the 2 groups (p=0.32). Our findings imply that both SP and NK1R are involved in the pathogenesis of chronic prurigo. Parallel groupdesigned trials are needed to assess the efficacy of topical aprepitant treatment in this condition.

Topics: Administration, Cutaneous; Aged; Aprepitant; Case-Control Studies; Chronic Disease; Double-Blind Method; Female; Humans; Male; Middle Aged; Morpholines; Neurokinin-1 Receptor Antagonists; Proof of Concept Study; Prospective Studies; Prurigo; Pruritus; Receptors, Neurokinin-1; Severity of Illness Index; Substance P; Visual Analog Scale

Atopic dermatitis (AD) is a chronic, itchy, inflammatory skin disorder that may worsen due to stress and anxiety. Tachykinins have been suggested to be involved in the inflammation in AD, as well as pruritus. Aprepitant is a NK-1 receptor antagonist. This open randomized trial evaluated the effect of aprepitant added to topical treatment in adult patients with moderate-severe AD. The treatment group (n = 19) received 80 mg/day aprepitant for 7 days as a supplement to standardized topical treatment with a moderately strong steroid and a moisturizer. The control group (n = 20) received topical treatment alone. Patients were monitored for the extent of the disease (using SCORing of Atopic Dermatitis; SCORAD), pruritus, and scratching movements. In both the aprepitant-treated and the control groups there was a decrease in SCORAD, pruritus and scratching movements. However, there was no significant additional improvement in any of these parameters in the aprepitant-treated group compared with the control group.

Topics: Administration, Cutaneous; Adult; Antipruritics; Aprepitant; Dermatitis, Atopic; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Morpholines; Neurokinin-1 Receptor Antagonists; Pruritus; Severity of Illness Index; Skin; Substance P; Sweden; Time Factors; Treatment Outcome; Young Adult

Topics: Aged; Aprepitant; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Middle Aged; Neurokinin-1 Receptor Antagonists; Pruritus; Sezary Syndrome; Skin Neoplasms; Treatment Failure

Topics: Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Antiemetics; Aprepitant; Double-Blind Method; Female; Histamine; Humans; Male; Middle Aged; Morpholines; Neurokinin-1 Receptor Antagonists; Pruritus; Severity of Illness Index; Water Loss, Insensible

Itch is a common side-effect of treatment with anti-EGFR antibodies and tyrosine-kinase inhibitors. We designed a pilot single-centre study to assess the effects of aprepitant-a neurokinin receptor inhibitor-for management of severe pruritus induced by biological drugs.. In this single-group, prospective study, we consecutively enrolled 45 outpatients with metastatic solid tumours treated with biological drugs at the Campus Bio-Medico Hospital of Rome, Rome, Italy, between September, 2010, and November, 2011. We classified patients into two groups: a refactory group, for patients with pruritis refractory to standard treatment, or a naive group, for patients who had not been previously treated for pruritis. Aprepitant (125 mg on day 1; 80 mg on day 3; 80 mg on day 5) was given to patients in the refractory group after at least 1 week of standard systemic treatment. In the naive group, aprepitant was given in the same schedule as the refractory group, after first onset of severe pruritus. Intensity of itch was evaluated by Visual Analogue Scale (VAS) score. The primary endpoint was change in median VAS score. This trial is registered with ClinicalTrials.gov, number NCT01683552.. Median VAS in the refractory group was 8·00 (95% CI 7·93-8·57) at baseline and 1·00 (0·00-2·00) after 1 week of treatment with aprepitant (p<0·0001). In the naive group, VAS score was 8·00 (7·43-8·37) at baseline and 0·00 (0·06-1·08) after 1 week of treatment (p<0·0001). 41 (91%) patients responded to aprepitant (ie, had a >50% reduction in intensity of pruritis) and pruritus recurred in only six (13%) patients. No adverse events related to aprepitant occurred.. Aprepitant decreases severe pruritus induced by biological treatments; it is an old drug, widely available, and therefore easy to add to the armamentarium of supportive treatment. Although to our knowledge no other studies of the anti-itch activity of aprepitant are planned, the results of our trial warrant confirmation in phase 2 and 3 trials.. None.

Topics: Adult; Aged; Antineoplastic Agents; Aprepitant; ErbB Receptors; Female; Humans; Male; Middle Aged; Morpholines; Neoplasms; Neurokinin-1 Receptor Antagonists; Pain Measurement; Pilot Projects; Prospective Studies; Pruritus

Topics: Aprepitant; Humans; Lymphoproliferative Disorders; Neurokinin-1 Receptor Antagonists; Pruritus

Topics: Antineoplastic Agents; Antipruritics; Aprepitant; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Lymphoma, T-Cell, Cutaneous; Neurokinin-1 Receptor Antagonists; Pruritus; Skin Neoplasms; Treatment Outcome

Topics: Administration, Cutaneous; Animals; Aprepitant; Behavior, Animal; Calcineurin Inhibitors; Dermatitis, Contact; Disease Models, Animal; Filaggrin Proteins; Ganglia, Spinal; Humans; Intermediate Filament Proteins; Male; Mice; Mice, Inbred BALB C; Mice, Transgenic; Ointments; Oxazolone; Oximes; Pruritus; Skin; Substance P; Tacrolimus; TRPA1 Cation Channel

Topics: Antipruritics; Aprepitant; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Lymphoma, T-Cell, Cutaneous; Pruritus; Retrospective Studies; Skin Neoplasms; Treatment Outcome

Topics: Antipruritics; Aprepitant; Humans; Lymphoma, T-Cell, Cutaneous; Pruritus; Skin Neoplasms

Although substantial progress has been made in the treatment of non-small-cell lung cancer (NSCLC) patients with immune checkpoint inhibitors (ICIs), severe immune-related adverse events (irAEs) sometimes occur. Here, we report a case of severe refractory pruritus after Stevens-Johnson syndrome (SJS) in a patient with NSCLC treated with nivolumab. The patient was a 76-year-old Japanese woman with advanced NSCLC treated with nivolumab. After the second dose, she experienced severe rash with mucous involvement. We diagnosed SJS and started 50mg of oral prednisolone (1mg/kg). The rash completely resolved after prednisolone was started, but we could not manage the severe pruritus with emollients, antihistamines, and steroids. Finally, we administered aprepitant, an oral neurokinin-1 receptor antagonist, for her refractory pruritus. Her symptoms improved within 5days. Severe refractory pruritus can arise from ICIs, and aprepitant may be a useful treatment.

Topics: Aged; Antibodies, Monoclonal; Antineoplastic Agents; Aprepitant; Carcinoma, Non-Small-Cell Lung; Female; Humans; Immunotherapy; Japan; Lung Neoplasms; Morpholines; Neurokinin-1 Receptor Antagonists; Nivolumab; Programmed Cell Death 1 Receptor; Pruritus; Remission Induction; Stevens-Johnson Syndrome

Pruritus is a major symptom of several dermatological diseases but has limited therapeutic options available. Animal models replicating the pathophysiology of pruritus are needed to support the development of new drugs. Induction of pruritus by chloroquine (CQ) in mice is widely used, although, as with similar models, it has low throughput and does not distinguish between antipruritic effects and confounding factors such as sedation. To overcome these issues, we incorporated into the model an automated system that measures both scratching and locomotor behaviour simultaneously. We combined this system with the determination of CQ levels in different tissues to understand the impact of the route of CQ administration on the pruritogenic response. We concluded that whereas oral CQ does not induce pruritus due to insufficient skin levels, the bell-shaped curve of pruritus observed following subcutaneous administration is due to toxicity at high doses. We validated the model with several drugs currently used in humans: nalfurafine, aprepitant, cyproheptadine and amitriptyline. By comparing the effects of the drugs on both scratching and locomotor activity, we concluded that nalfurafine and aprepitant can exhibit efficacy at doses devoid of central effects, whereas central effects drove the efficacy of the other two drugs. This was further confirmed using non-brain-penetrant drugs. Moreover, as anticipated, anti-inflammatory drugs showed no efficacy. In conclusion, the use of an automated integrated behavioural assessment in CQ-induced pruritus makes the assay suitable for screening purposes and allows for a correct interpretation of the antipruritic effect of the compounds evaluated.

Topics: Administration, Oral; Amitriptyline; Animals; Anti-Inflammatory Agents; Antidepressive Agents, Tricyclic; Antipruritics; Aprepitant; Behavior, Animal; Chloroquine; Cyproheptadine; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Routes; Injections, Subcutaneous; Male; Mice; Mice, Inbred C57BL; Morphinans; Morpholines; Motor Activity; Narcotic Antagonists; Neurokinin-1 Receptor Antagonists; Pattern Recognition, Automated; Pruritus; Signal Processing, Computer-Assisted; Skin; Spiro Compounds; Vibration; Video Recording

Experiments were conducted to develop a model to study the effect of oral and topical administration of the NK1 receptor antagonist aprepitant, on scratching behaviour in gerbils. The gerbil was selected due to its relevance for human NK1 receptor pharmacology. Intradermal injection of a specific NK1 receptor agonist GR73632 (100 nmol/100 µl) at the rostral back of gerbils produced scratching of the injection site. This could be attenuated by intradermal co-administration of a selective NK1 receptor antagonist aprepitant (30-100-300 nmol), demonstrating the role of dermal NK1 receptor in elicitation of scratching behaviour. Likewise, scratching was attenuated by oral (0.3-3-30 mg/kg) or topical application (0.01-0.1-1% w/v) of aprepitant and pharmacokinetic analysis of aprepitant levels in brain, blood and skin supported that efficacy of topically applied aprepitant was due to dermal rather than central target engagement. In conclusion, we showed that NK1 agonist-induced scratching in the gerbil can be reversed by systemic and topical administration of aprepitant. This test system may provide a useful model for the in vivo assessment of putative antipruritic agents.

Topics: Administration, Oral; Administration, Topical; Animals; Antipruritics; Aprepitant; Disease Models, Animal; Drug Evaluation, Preclinical; Gerbillinae; Humans; Injections, Intradermal; Morpholines; Neurokinin-1 Receptor Antagonists; Peptide Fragments; Pruritus; Receptors, Neurokinin-1; Substance P

Topics: Aprepitant; Female; Humans; Lymphoma, T-Cell, Cutaneous; Middle Aged; Morpholines; Pruritus; Skin Neoplasms

Immunologic responses in the skin can be modulated by such neurotransmitters of sensory nerve fibers as substance P (SP) and calcitonin gene-related peptide (CGRP). The first-generation receptor antagonists were peptides with large molecules and had to be injected intracutaneously. The aim of this study was to examine the topical effects of non-peptide antagonists to substance P (aprepitant) and CGRP (telcagepant), respectively, on delayed and immediate reactions in the skin and on associated pruritus. A lipophilic formulation of aprepitant 5% and a hydrophilic formulation of telcagepant 1% were developed. Their effect on the skin barrier was measured in terms of transepidermal water loss (TEWL) while permeation was calculated using permeation coefficients. Patch tests in patients allergic to nickel and prick test reactions to histamine were used as models. None of the treatments increased TEWL, suggesting there to be no impairment of the skin barrier. Permeation coefficients indicated moderate permeation. Histamine prick tests induced a flare with a mean area of 662 + 275 mm(2) and a weal with a mean volume of 49 + 11 mm(3). These reactions as well as histamine-induced pruritus were not affected significantly by any of the treatments. Treatment with aprepitant and its vehicle alone resulted in a potentiating of the infiltration of nickel reactions compared with test reactions obtained after no treatment (1147 + 423 mm(3) and 1427 + 566 mm(3) vs 683 +202 mm(3)) (p = 0.03). Telcagepant induced vasoconstriction in the skin but did not change the infiltration of nickel reactions. None of the treatments influenced the nickel patch test induced pruritus. The data suggest that the topical application of non-peptide antagonists penetrates the skin but does not inhibit contact dermatitis or pruritus.

Topics: Adult; Aged; Antipruritics; Aprepitant; Azepines; Calcitonin Gene-Related Peptide; Dermatitis, Contact; Double-Blind Method; Female; Humans; Hypersensitivity, Delayed; Imidazoles; Male; Middle Aged; Morpholines; Nickel; Permeability; Pilot Projects; Pruritus; Skin; Skin Physiological Phenomena; Skin Tests; Substance P; Urticaria; Vasoconstriction; Water Loss, Insensible; Young Adult

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Topics: Aged; Aprepitant; Humans; Lymphoma, T-Cell, Cutaneous; Male; Morpholines; Neurokinin-1 Receptor Antagonists; Pruritus; Skin Neoplasms

Paraneoplastic pruritus is defined as pruritus that occurs before or during the natural evolution of a hematologic disease. The reported prevalence is 30% in patients with Hodgkin's lymphoma. The severity of this pruritus has a very negative impact on patients' quality of life. Very few studies have been made to examine the efficacy of pharmacological treatments for this type of pruritus. One drug that appears to be effective in this respect is off-label aprepitant, a neurokinin 1 receptor antagonist.. A 20-year-old Caucasian woman presented with lateral neck nodes, sweating, and pruritus and was diagnosed with stage IIB nodular sclerosis Hodgkin's lymphoma. Throughout this period during the disease the pruritus was ever-present. Improvement was achieved with some of the chemotherapy treatments, but the symptom returned when the various treatments were withdrawn due to disease progression or poor tolerance. In the middle of the seventh year, she was admitted to our hospital with uncontrolled pruritus that resulted in severe lesions due to scratching. In response, aprepitant (off-label) 80 mg/day was added to the chemotherapic treatment of the pruritus, after studying the various treatment options. She reported a score of 9 on a visual analogue scale for the pruritus, and a score of 3 on the Eastern Cooperative Oncology Group performance status scale of performance status. After two weeks of treatment with aprepitant, she reported a score of 5 on the visual analogue scale for the pruritus, and this improved to a score of 4 in a month, which allowed her to lead a better quality of life, with an Eastern Cooperative Oncology Group performance status score between 1 and 2.. Several cases and case series have been reported on the use of aprepitant for paraneoplastic pruritus, but none have referred to its use for Hodgkin's lymphoma. A prospective study was carried out to evaluate the efficacy of this drug in refractory pruritus secondary to Sezary syndrome, and other authors have studied the effectiveness of aprepitant against pruritus, secondary to biological therapy with erlotinib. In our case report, treatment was started with daily doses of aprepitant 80 mg. Pruritus improvement appeared to be attributable exclusively to the administration of aprepitant.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Female; Hodgkin Disease; Humans; Morpholines; Neurokinin-1 Receptor Antagonists; Pruritus; Treatment Outcome; Young Adult

Topics: Antipruritics; Aprepitant; Female; Forearm; Humans; Middle Aged; Morpholines; Pruritus

Topics: Aprepitant; Chronic Disease; Humans; Morpholines; Neurokinin-1 Receptor Antagonists; Pruritus; Sezary Syndrome

Topics: Antineoplastic Agents; Aprepitant; ErbB Receptors; Female; Humans; Male; Morpholines; Neoplasms; Neurokinin-1 Receptor Antagonists; Pruritus

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Humans; Morpholines; Pruritus

Topics: Administration, Oral; Aged; Antipruritics; Aprepitant; Female; Humans; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Morpholines; Neurokinin-1 Receptor Antagonists; Prospective Studies; Pruritus; Quality of Life; Surveys and Questionnaires

Topics: Antiemetics; Aprepitant; Erlotinib Hydrochloride; Humans; Morpholines; Neurokinin-1 Receptor Antagonists; Off-Label Use; Protein Kinase Inhibitors; Pruritus; Quinazolines; Substance P

Topics: Adenocarcinoma; Aprepitant; Drug Interactions; Drug Therapy, Combination; Erlotinib Hydrochloride; Humans; Lung Neoplasms; Middle Aged; Morpholines; Neurokinin-1 Receptor Antagonists; Off-Label Use; Protein Kinase Inhibitors; Pruritus; Quinazolines

Chronic pruritus is a global clinical problem with a high impact on the quality of life and lack of specific therapies. It is an excruciating and frequent symptom of e.g. uncurable renal, liver and skin diseases which often does not respond to conventional treatment with e.g. antihistamines. Therefore antipruritic therapies which target physiological mechanisms of pruritus need to be developed. Substance P (SP) is a major mediator of pruritus. As it binds to the neurokinin receptor 1 (NKR1), we evaluated if the application of a NKR1 antagonist would significantly decrease chronic pruritus.. Twenty hitherto untreatable patients with chronic pruritus (12 female, 8 male; mean age, 66.7 years) were treated with the NKR1 antagonist aprepitant 80 mg for one week. 16 of 20 patients (80%) experienced a considerable reduction of itch intensity, as assessed by the visual analog scale (VAS, range 0 to 10). Considering all patients, the mean value of pruritus intensity was significantly reduced from 8.4 VAS points (SD +/-1.7) before treatment to 4.9 VAS points (SD +/-3.2) (p<0.001, CI 1.913-5.187). Patients with dermatological diseases (e.g. atopic diathesis, prurigo nodularis) had the best profit from the treatment. Side-effects were mild (nausea, vertigo, and drowsiness) and only occurred in three patients.. The high response rate in patients with therapy refractory pruritus suggests that the NKR1 antagonist aprepitant may indeed exhibit antipruritic effects and may present a novel, effective treatment strategy based on pathophysiology of chronic pruritus. The results are promising enough to warrant confirming the efficacy of NKR1 antagonists in a randomized, controlled clinical trial.

Topics: Aged; Aged, 80 and over; Aprepitant; Chronic Disease; Female; Humans; Male; Middle Aged; Morpholines; Pruritus; Receptors, Neurokinin-1; Treatment Outcome

Topics: Antiemetics; Aprepitant; Female; Humans; Male; Morpholines; Neoplasms; Pruritus; Receptors, Neurokinin-1

Topics: Adult; Aged; Aprepitant; Erlotinib Hydrochloride; Female; Humans; Male; Morpholines; Neurokinin-1 Receptor Antagonists; Protein Kinase Inhibitors; Pruritus; Quinazolines

Topics: Antineoplastic Agents; Aprepitant; Area Under Curve; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Drug Administration Schedule; Drug Interactions; Erlotinib Hydrochloride; Humans; Morpholines; Neurokinin-1 Receptor Antagonists; Off-Label Use; Protein Kinase Inhibitors; Pruritus; Quinazolines

Topics: Antiemetics; Aprepitant; Humans; Morpholines; Neurokinin-1 Receptor Antagonists; Pruritus; Sezary Syndrome; Skin Neoplasms