Pruritus and Systemic Disease Medication
- Author: David F Butler, MD; Chief Editor: William D James, MD more...
The goals of pharmacotherapy are to reduce morbidity and prevent complications.
These agents are used to treat renal pruritus.
Activated charcoal is the drug of choice for the initial treatment of renal pruritus. Its mechanism of action is unknown, but it is thought to bind an unknown pruritogen. Sorbitol and flavoring are added to some forms to enhance palatability.
Topical agents are used to treat localized renal pruritus.
Capsaicin is derived from plants of the Solanaceae family. It may render skin and joints insensitive to pain and pruritus by depleting substance P in peripheral sensory neurons, decreasing the transmission of sensation. If is for localized pruritus only.
Immunomodulatory agents are used to treat recalcitrant renal or cholestatic pruritus.
Thalidomide is thought to decrease T helper cells while inhibiting the production of TNF-alpha, which may induce itching. It has a strong central depressant effect that may decrease pruritus. Because of adverse events, attempt other treatments first.
Bile Acid Lowering Agents
These agents are used to treat cholestatic pruritus.
Cholestyramine is an anion-exchange resin that binds bile acids in the GI tract, interrupting their enterohepatic circulation; it is primarily used to lower cholesterol. Patients must have adequate bile flow for the drug to be effective. Consider this therapy early in cases of hepatic cholestasis because it is inexpensive and may provide relief (within 1-3 wk). Pruritus returns within weeks of discontinuation.
Ursodeoxycholic acid/ursodiol is a hydrophilic bile acid that alters the hydrophilicity and distribution of total bile acids and increases the excretion of hydrophobic bile acids. It decreases damage to the hepatocyte membrane by decreasing the uptake of hydrophobic bile acids at the terminal ileum (and likely in hepatocytes). Ursodeoxycholic acid/ursodiol is first-line treatment for patients with intrahepatic cholestasis of pregnancy; it normalizes laboratory values and decreases morbidity and mortality to the fetus by reducing exposure to bile acids.
Hepatic enzyme inducing agents
These agents are used to treat cholestatic pruritus.
Rifampin is traditionally used as an antibiotic with the known mechanism of action of inhibiting RNA synthesis in bacteria. It also inhibits the reuptake of hepatic bile acid and induces hepatic mixed-function oxidases, which may detoxify hepatic bile acids. Consider this drug when a course of cholestyramine fails.
Opioid antagonist agents
These agents are used to treat cholestatic pruritus.
Naloxone is an opioid antagonist and is given intravenously; therefore, it should only be used in emergency treatment of exacerbations of cholestatic pruritus in a hospital setting. A low-dose infusion may be used for 24 hours before oral naltrexone or nalmefene to avoid opioid withdrawal syndrome (sometimes seen in patients given oral opioid antagonists).
Naltrexone may also be considered if patients with cholestatic pruritus do not respond to cholestyramine and rifampin. Naltrexone can be administered orally and has a longer half-life than naloxone.
Anti-inflammatory agents are used to treat polycythemia rubra vera.
Aspirin appears to decrease platelet degranulation of serotonin and prostaglandins, which contribute to pruritus. It is first-line treatment for symptomatic control of pruritus related to polycythemia vera. Relief may last 12-24 hours.
These drugs are used to treat generalized pruritus in patients with advanced cancer or polycythemia vera.
Mirtazapine is a relatively new antidepressant and is not as widely used as sertraline. It exhibits both noradrenergic and serotonergic activity. In cases of depression associated with severe insomnia and anxiety, mirtazapine has been shown to be superior to other SSRI drugs.
Paroxetine is a potent selective inhibitor of neuronal serotonin reuptake. Its mechanism of relieving pruritus is unknown. Effects occur within a few days but may last only 4-6 weeks.
Doxepin is a TCA that has potent H1-blocking activity, making it quite useful for urticaria. However, it has very potent sedative and anticholinergic effects. It can be quite effective if used at bedtime because the sedative effects can help a patient with pruritus sleep.
Analgesic opioid agents
Agents with central analgesic action may be useful. May alter perception and response to varied stimuli.
Butorphanol is a mixed agonist-antagonist narcotic with central analgesic effects for moderate to severe pain. It causes less smooth muscle spasm and respiratory depression than morphine or meperidine. Weigh the advantages against the increased cost of butorphanol.
These agents may prevent release of inflammatory cytokines from mast cells.
Pimecrolimus is the first nonsteroid cream approved in United States for mild-to-moderate atopic dermatitis. It is derived from ascomycin, a natural substance produced by the fungus Streptomyces hygroscopicus var ascomyceticus. It selectively inhibits the production and release of inflammatory cytokines from activated T cells by binding to the cytosolic immunophilin receptor macrophilin-12. The resulting complex inhibits phosphatase calcineurin, thus blocking T-cell activation and cytokine release. Cutaneous atrophy has not been observed in clinical trials, a potential advantage over topical corticosteroids. Pimecrolimus is indicated only after other treatment options have failed. Use short-term and for intermittent use only.
Cho YL, Liu HN, Huang TP, Tarng DC. Uremic pruritus: roles of parathyroid hormone and substance P. J Am Acad Dermatol. 1997 Apr. 36(4):538-43. [Medline].
Tarikci N, Kocatürk E, Güngör Ş, Topal IO, Can PÜ, Singer R. Pruritus in Systemic Diseases: A Review of Etiological Factors and New Treatment Modalities. ScientificWorldJournal. 2015. 2015:803752. [Medline].
Cowden JM, Zhang M, Dunford PJ, Thurmond RL. The histamine H4 receptor mediates inflammation and pruritus in Th2-dependent dermal inflammation. J Invest Dermatol. 2010 Apr. 130(4):1023-33. [Medline].
Chou FF, Ho JC, Huang SC, Sheen-Chen SM. A study on pruritus after parathyroidectomy for secondary hyperparathyroidism. J Am Coll Surg. 2000 Jan. 190(1):65-70. [Medline].
Hampers CL, Katz AI, Wilson RE, Merrill JP. Disappearance of "uremic" itching after subtotal parathyroidectomy. N Engl J Med. 1968 Sep 26. 279(13):695-7. [Medline].
Massry SG, Popovtzer MM, Coburn JW, Makoff DL, Maxwell MH, Kleeman CR. Intractable pruritus as a manifestation of secondary hyperparathyroidism in uremia. Disappearance of itching after subtotal parathyroidectomy. N Engl J Med. 1968 Sep 26. 279(13):697-700. [Medline].
Graf H, Kovarik J, Stummvoll HK, Wolf A. Disappearance of uraemic pruritus after lowering dialysate magnesium concentration. Br Med J. 1979 Dec 8. 2(6203):1478-9. [Medline].
Kyriazis J, Glotsos J. Dialysate calcium concentration of</=1.25>Nephron</i>. 2000 Jan. 84(1):85-6. [Medline].
Zucker I, Yosipovitch G, David M, Gafter U, Boner G. Prevalence and characterization of uremic pruritus in patients undergoing hemodialysis: uremic pruritus is still a major problem for patients with end-stage renal disease. J Am Acad Dermatol. 2003 Nov. 49(5):842-6. [Medline].
Kumagai H, Ebata T, Takamori K, Muramatsu T, Nakamoto H, Suzuki H. Effect of a novel kappa-receptor agonist, nalfurafine hydrochloride, on severe itch in 337 haemodialysis patients: a Phase III, randomized, double-blind, placebo-controlled study. Nephrol Dial Transplant. 2010 Apr. 25(4):1251-7. [Medline].
Phan NQ, Bernhard JD, Luger TA, Ständer S. Antipruritic treatment with systemic μ-opioid receptor antagonists: a review. J Am Acad Dermatol. 2010 Oct. 63 (4):680-8. [Medline].
Kremer AE, Martens JJ, Kulik W, Ruëff F, Kuiper EM, van Buuren HR, et al. Lysophosphatidic acid is a potential mediator of cholestatic pruritus. Gastroenterology. 2010 Sep. 139 (3):1008-18, 1018.e1. [Medline].
Diehn F, Tefferi A. Pruritus in polycythaemia vera: prevalence, laboratory correlates and management. Br J Haematol. 2001 Dec. 115 (3):619-21. [Medline].
Fett N, Haynes K, Propert KJ, Margolis DJ. Five-year malignancy incidence in patients with chronic pruritus: a population-based cohort study aimed at limiting unnecessary screening practices. J Am Acad Dermatol. 2014 Apr. 70 (4):651-8. [Medline].
Rowe B, Yosipovitch G. Malignancy-associated pruritus. Eur J Pain. 2016 Jan. 20 (1):19-23. [Medline].
Hundley JL, Yosipovitch G. Mirtazapine for reducing nocturnal itch in patients with chronic pruritus: a pilot study. J Am Acad Dermatol. 2004 Jun. 50(6):889-91. [Medline].
Demierre MF, Taverna J. Mirtazapine and gabapentin for reducing pruritus in cutaneous T-cell lymphoma. J Am Acad Dermatol. 2006 Sep. 55(3):543-4. [Medline].
Anand S. Gabapentin for Pruritus in Palliative Care. Am J Hosp Palliat Care. 2012 May 2. [Medline].
Stander S, Siepmann D, Herrgott I, Sunderkotter C, Luger TA. Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy. PLoS One. 2010 Jun 4. 5(6):e10968. [Medline]. [Full Text].
Yosipovitch G, Maibach HI, Rowbotham MC. Effect of EMLA pre-treatment on capsaicin-induced burning and hyperalgesia. Acta Derm Venereol. 1999 Mar. 79(2):118-21. [Medline].
Kuypers DR, Claes K, Evenepoel P, Maes B, Vanrenterghem Y. A prospective proof of concept study of the efficacy of tacrolimus ointment on uraemic pruritus (UP) in patients on chronic dialysis therapy. Nephrol Dial Transplant. 2004 Jul. 19(7):1895-901. [Medline].
Chen YC, Chiu WT, Wu MS. Therapeutic effect of topical gamma-linolenic acid on refractory uremic pruritus. Am J Kidney Dis. 2006 Jul. 48(1):69-76. [Medline].
Boardman LA, Cooper AS, Blais LR, Raker CA. Topical gabapentin in the treatment of localized and generalized vulvodynia. Obstet Gynecol. 2008 Sep. 112(3):579-85. [Medline].
Blachley JD, Blankenship DM, Menter A, Parker TF 3rd, Knochel JP. Uremic pruritus: skin divalent ion content and response to ultraviolet phototherapy. Am J Kidney Dis. 1985 May. 5(5):237-41. [Medline].
Gilchrest BA, Rowe JW, Brown RS, Steinman TI, Arndt KA. Ultraviolet phototherapy of uremic pruritus. Long-term results and possible mechanism of action. Ann Intern Med. 1979 Jul. 91(1):17-21. [Medline].
Giovannetti S, Barsotti G, Cupisti A, et al. Oral activated charcoal in patients with uremic pruritus. Nephron. 1995. 70(2):193-6. [Medline].
Hiroshige K, Kabashima N, Takasugi M, Kuroiwa A. Optimal dialysis improves uremic pruritus. Am J Kidney Dis. 1995 Mar. 25(3):413-9. [Medline].
Pederson JA, Matter BJ, Czerwinski AW, Llach F. Relief of idiopathic generalized pruritus in dialysis patients treated with activated oral charcoal. Ann Intern Med. 1980 Sep. 93(3):446-8. [Medline].
Jedras M, Zakrzewska-Pniewska B, Wardyn K, Switalski M. [Uremic neuropathy--II. Is pruritus in dialyzed patients related to neuropathy?]. Pol Arch Med Wewn. 1998 Jun. 99(6):462-9. [Medline].
Silva SR, Viana PC, Lugon NV, Hoette M, Ruzany F, Lugon JR. Thalidomide for the treatment of uremic pruritus: a crossover randomized double-blind trial. Nephron. 1994. 67(3):270-3. [Medline].
Legroux-Crespel E, Cledes J, Misery L. A comparative study on the effects of naltrexone and loratadine on uremic pruritus. Dermatology. 2004. 208(4):326-30. [Medline].
Pauli-Magnus C, Mikus G, Alscher DM, et al. Naltrexone does not relieve uremic pruritus: results of a randomized, double-blind, placebo-controlled crossover study. J Am Soc Nephrol. 2000 Mar. 11(3):514-9. [Medline].
Balaskas EV, Uldall RP. Erythropoietin treatment does not improve uremic pruritus. Perit Dial Int. 1992. 12(3):330-1. [Medline].
De Marchi S, Cecchin E, Villalta D, Sepiacci G, Santini G, Bartoli E. Relief of pruritus and decreases in plasma histamine concentrations during erythropoietin therapy in patients with uremia. N Engl J Med. 1992 Apr 9. 326(15):969-74. [Medline].
Manenti L, Vaglio A, Costantino E, et al. Gabapentin in the treatment of uremic itch: an index case and a pilot evaluation. J Nephrol. 2005 Jan-Feb. 18(1):86-91. [Medline].
Dawn AG, Yosipovitch G. Butorphanol for treatment of intractable pruritus. J Am Acad Dermatol. 2006 Mar. 54(3):527-31. [Medline].
Najafabadi MM, Faghihi G, Emami A, et al. Zinc sulfate for relief of pruritus in patients on maintenance hemodialysis. Ther Apher Dial. 2012 Apr. 16(2):142-5. [Medline].
Cynamon HA, Andres JM, Iafrate RP. Rifampin relieves pruritus in children with cholestatic liver disease. Gastroenterology. 1990 Apr. 98(4):1013-6. [Medline].
Ghent CN, Carruthers SG. Treatment of pruritus in primary biliary cirrhosis with rifampin. Results of a double-blind, crossover, randomized trial. Gastroenterology. 1988 Feb. 94(2):488-93. [Medline].
Bergasa NV, Alling DW, Talbot TL, et al. Effects of naloxone infusions in patients with the pruritus of cholestasis. A double-blind, randomized, controlled trial. Ann Intern Med. 1995 Aug 1. 123(3):161-7. [Medline].
Peer G, Kivity S, Agami O, et al. Randomised crossover trial of naltrexone in uraemic pruritus. Lancet. 1996 Dec 7. 348(9041):1552-4. [Medline].
Terg R, Coronel E, Sorda J, Munoz AE, Findor J. Efficacy and safety of oral naltrexone treatment for pruritus of cholestasis, a crossover, double blind, placebo-controlled study. J Hepatol. 2002 Dec. 37(6):717-22. [Medline].
Wolfhagen FH, Sternieri E, Hop WC, Vitale G, Bertolotti M, Van Buuren HR. Oral naltrexone treatment for cholestatic pruritus: a double-blind, placebo-controlled study. Gastroenterology. 1997 Oct. 113(4):1264-9. [Medline].
Bergasa NV, Alling DW, Talbot TL, Wells MC, Jones EA. Oral nalmefene therapy reduces scratching activity due to the pruritus of cholestasis: a controlled study. J Am Acad Dermatol. 1999 Sep. 41(3 Pt 1):431-4. [Medline].
Palma J, Reyes H, Ribalta J, et al. Ursodeoxycholic acid in the treatment of cholestasis of pregnancy: a randomized, double-blind study controlled with placebo. J Hepatol. 1997 Dec. 27(6):1022-8. [Medline].
Roncaglia N, Locatelli A, Arreghini A, et al. A randomised controlled trial of ursodeoxycholic acid and S-adenosyl-l-methionine in the treatment of gestational cholestasis. BJOG. 2004 Jan. 111(1):17-21. [Medline].
Bellmann R, Feistritzer C, Zoller H, et al. Treatment of intractable pruritus in drug induced cholestasis with albumin dialysis: a report of two cases. ASAIO J. 2004 Jul-Aug. 50(4):387-91. [Medline].
Bellmann R, Graziadei IW, Feistritzer C, et al. Treatment of refractory cholestatic pruritus after liver transplantation with albumin dialysis. Liver Transpl. 2004 Jan. 10(1):107-14. [Medline].
Hernandez-Nunez A, Dauden E, Cordoba S, Aragues M, Garcia-Diez A. Water-induced pruritus in haematologically controlled polycythaemia vera: response to phototherapy. J Dermatolog Treat. 2001 Jun. 12(2):107-9. [Medline].
Morison WL, Nesbitt JA 3rd. Oral psoralen photochemotherapy (PUVA) for pruritus associated with polycythemia vera and myelofibrosis. Am J Hematol. 1993 Apr. 42(4):409-10. [Medline].
Finelli C, Gugliotta L, Gamberi B, Vianelli N, Visani G, Tura S. Relief of intractable pruritus in polycythemia vera with recombinant interferon alfa. Am J Hematol. 1993 Aug. 43(4):316-8. [Medline].
Gonçalves F. Thalidomide for the Control of Severe Paraneoplastic Pruritus Associated With Hodgkin's Disease. Am J Hosp Palliat Care. 2010 Mar 15. [Medline].
Gutman AB, Kligman AM, Sciacca J, James WD. Soak and smear: a standard technique revisited. Arch Dermatol. 2005 Dec. 141 (12):1556-9. [Medline].