rifampin and Pruritus

Pruritus in cholestatic liver diseases can be a major burden and dramatically impair the quality of life of those affected. Here, we provide an update on the latest insights into the molecular pathogenesis of and novel therapeutic approaches for cholestasis-associated itch. Endogenous and exogenous small-molecule pruritogen candidates bind to their receptors on unmyelinated itch C-fibres in the skin. Candidate pruritogens in cholestasis include certain lysophospholipids and sulfated progesterone metabolites, among others, whereas total bile acid or bilirubin conjugates seem unlikely to have a dominant role in the pathogenesis of cholestasis-associated pruritus. Transmission of itch signals via primary, secondary and tertiary itch neurons to the postcentral gyrus and activation of scratch responses offer various targets for therapeutic intervention. At present, evidence-based treatment options for pruritus in fibrosing cholangiopathies, such as primary biliary cholangitis and primary sclerosing cholangitis, are the peroxisome proliferator-associated receptor (PPAR) agonist bezafibrate and the pregnane X receptor (PXR) agonist rifampicin. In pruritus of intrahepatic cholestasis of pregnancy, ursodeoxycholic acid is recommended and might be supported in the third trimester by rifampicin if needed. Alternatively, non-absorbable anion exchange resins, such as cholestyramine, can be administered, albeit with poor trial evidence. Liver transplantation for intolerable refractory pruritus has become an extremely rare therapeutic strategy.

Topics: Cholestasis; Cholestasis, Intrahepatic; Cholestyramine Resin; Female; Humans; Pregnancy; Pruritus; Quality of Life; Rifampin

Chronic pruritus is a classic symptom in patients with primary biliary cholangitis. It affects up to two-thirds of patients in the course of the disease. Efficient therapy consists of topical treatment combined with systemic options such as anion exchangers, rifampicin, bezafibrate, μ-opioid receptor antagonists, selective-serotonin receptor uptake inhibitors, and gabapentinoids. Future therapeutic approaches may contain the selective blockade of the enterohepatic cycle by inhibiting the ileal bile acid transporter, the agonism at κ-opioid receptors, and antagonism of the mas-related G protein-coupled receptor X4. As nondrug treatment, ultraviolet B therapy, albumin dialysis, and biliary drainage are available at specialized centers.

Topics: Albumins; Bezafibrate; Humans; Liver Cirrhosis, Biliary; Narcotic Antagonists; Pruritus; Receptors, Opioid; Receptors, Serotonin; Rifampin; Selective Serotonin Reuptake Inhibitors

Hepatic itch remains among the most agonizing symptoms for affected patients and a major clinical challenge for physicians. Pruritus may occur in almost all liver diseases, particularly those with cholestatic features. Hepatic itch arises irrespective of the severity of the underlying liver disease or extent of cholestasis. Antihistamines are ineffective in hepatic itch. Therapeutic recommendations consist of a guideline-based stepwise approach, starting with the anion exchange resin cholestyramine, followed by rifampicin, naltrexone, and sertraline. Bezafibrate and ileal bile acid transporter inhibitors are promising future treatment options. Experimental and invasive procedures should be reserved for refractory pruritus.

Topics: Analgesics, Opioid; Anion Exchange Resins; Antipruritics; Bezafibrate; Carrier Proteins; Cholagogues and Choleretics; Cholestasis; Cholestyramine Resin; Chronic Disease; Cytochrome P-450 Enzyme Inducers; Drainage; Humans; Hypolipidemic Agents; Membrane Glycoproteins; Methylamines; Narcotic Antagonists; Prevalence; Pruritus; Rifampin; Thiazepines; Ursodeoxycholic Acid

Pruritus is a common symptom with primary biliary cholangitis. Research has focused on refining understanding of the neurohumoral pathways involved in transduction of pruritus from peripheral cutaneous receptors to the central nervous system, and identifying modulating drugs. Current treatments have variable efficacy and safety. Because of the deleterious effects on quality of life or debilitation, many patients necessitate individualized therapeutic approaches; clinicians may need to consider invasive treatment options. This article highlights various therapeutic interventions, from general measures to invasive strategies, and novel agents under investigation, providing clinicians with the management tricks of the trade.

Topics: Anion Exchange Resins; Bile Acids and Salts; Cholestyramine Resin; Drainage; Filtration; Humans; Liver Cirrhosis, Biliary; Lysophospholipids; Narcotic Antagonists; Opioid Peptides; Phosphoric Diester Hydrolases; Plasmapheresis; Pruritus; Receptors, Opioid; Rifampin; Selective Serotonin Reuptake Inhibitors; Serotonin; Sertraline; Substance P

Pruritus is a disabling symptom accompanying chronic cholestasis. In some cases, refractory pruritus may require invasive therapies including liver transplantation. The pathogenesis of pruritus in cholestatic disease is poorly understood. It may involve a specific neural pathway and several pruritogenic substances such as bile acids, opioids, serotonin, and the more recently identified lysophosphatidic acid. While the therapeutic management of cholestatic pruritus is well established in adult patients, there is no consensus in children, given the difficulty in conducting controlled clinical studies. The currently recommended strategy to manage cholestatic pruritus in children is based on several lines of therapy that should always be associated with local cutaneous care and with nonspecific treatment of cholestasis including ursodeoxycholic acid therapy. Pruritus should be assessed as objectively as possible between each therapeutic step. Rifampicin, an enzyme inducer, is the specific first-line treatment of cholestatic pruritus. The second-line therapies require evaluation of the child in an expert center and are discussed on a case-by-case basis depending on the underlying disease, the experience of the center and the will of the child and his family. It could be inhibitors of serotonin reuptake (sertraline) or an opioid antagonist (naloxone). Invasive therapies such as biliary diversion or liver transplantation can also be proposed in the most severe cases.

Topics: Anion Exchange Resins; Biliary Tract Surgical Procedures; Child; Cholagogues and Choleretics; Cholestasis; Cholestyramine Resin; Chronic Disease; Cytochrome P-450 CYP3A Inducers; Humans; Liver Transplantation; Narcotic Antagonists; Pruritus; Rifampin; Selective Serotonin Reuptake Inhibitors; Sertraline; Sorption Detoxification; Ursodeoxycholic Acid

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

Cholestatic itch is a feature of numerous hepatobiliary disorders such as primary biliary cirrhosis, primary sclerosing cholangitis, the inherited form of cholestasis, and intrahepatic cholestasis of pregnancy. Although undervalued by physicians, cholestatic itch can be a source of great discomfort to the patient and significantly affects quality of life. Many pruritogens such as bile salts, opioids, serotonin, and histamine have been implicated in the pathogenesis of cholestatic itch, but no causative link has ever been established. Recent findings indicate that the potent neuronal activator lysophosphatidic acid and autotaxin, the enzyme forming lysophosphatidic acid, may be key elements in its pathogenesis. Treatment options for patients with cholestatic itch include the anion exchange resin cholestyramine, bile acid ursodeoxycholic acid, PXR agonist rifampicin, opioid antagonist naltrexone, and the serotonin inhibitor sertraline. These drugs can be used as a stepwise therapeutic approach. The body of evidence for many of these options, however, is not very robust. Patients who do not respond to medical therapy can be candidates for interventional measures, such as albumin dialysis, plasmapheresis, or nasobiliary drainage, or certain experimental approaches such as UVB phototherapy. Research over the past decade has elucidated many of the receptors and neuropeptides involved in itch sensation and transmission; it is hoped that in the future this will lead to the development of novel antipruritic medication for cholestatic itch.

Topics: Anion Exchange Resins; Cholagogues and Choleretics; Cholestasis; Cholestyramine Resin; Humans; Lysophospholipids; Naltrexone; Narcotic Antagonists; Plasmapheresis; Pregnane X Receptor; Pruritus; Receptors, Steroid; Rifampin; Selective Serotonin Reuptake Inhibitors; Sertraline; Ultraviolet Therapy; Ursodeoxycholic Acid

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease during pregnancy, characterized by otherwise unexplained pruritus in late second and third trimester of pregnancy and elevated bile acids and/or transaminases. ICP is associated with an increased risk of adverse perinatal outcomes for the fetus and the later development of hepatobiliary disease for the mother. Bile acids should be monitored throughout pregnancy since fetal risk is increased at serum bile acids >40 µmol/l. Management of ICP consists of treatment with ursodeoxycholic acid, which reduces pruritus. Early elective delivery is common practice but should be performed on an individualized basis as long as strong evidence supporting this practice is lacking. Mothers should be followed-up for normalization of liver function tests 6-12 weeks after delivery. Future research in large-scale studies is needed to address the impact of ursodeoxycholic acid and early elective delivery on fetal outcome.

Topics: Antifibrinolytic Agents; Bile Acids and Salts; Cholagogues and Choleretics; Cholestasis, Intrahepatic; Female; Fetal Death; Histamine Antagonists; Humans; Labor, Induced; Nucleic Acid Synthesis Inhibitors; Pregnancy; Pregnancy Complications; Premature Birth; Pruritus; Rifampin; Ursodeoxycholic Acid; Vitamin K

The pathogenesis of itch during cholestasis is largely unknown and treatment options are limited. Lysophosphatidate, female steroid hormones, and endogenous opioids are among the agents discussed as potential pruritogens in cholestasis. The itch-alleviating action of guideline-based therapeutic interventions with anion exchanger resins, rifampicin, opioid antagonists, and serotonin reuptake inhibitors are studied to unravel the molecular pathogenesis of itch. Still, a considerable part of the patients is in need of alternative experimental therapeutic approaches (eg, UV-B phototherapy, extracorporeal albumin dialysis, nasobiliary drainage), providing additional information about the enigmatic pathophysiology of cholestatic pruritus.

Topics: Animals; Anion Exchange Resins; Antibiotics, Antitubercular; Bile Acids and Salts; Cholestasis; Cholestyramine Resin; Humans; Lysophospholipids; Narcotic Antagonists; Pregnane X Receptor; Pruritus; Receptors, Steroid; Rifampin; Selective Serotonin Reuptake Inhibitors; Sertraline; Signal Transduction

Pruritus can be the dominant symptom of cholestatic liver disease but is difficult to treat since unraveling its pathophysiology is a great challenge. Serum autotaxin activity correlates with pruritus intensity, but its causal relationship, expression pattern and exact mode of action during cholestasis remain to be established. The anion exchange resin cholestyramine, the PXR agonist rifampicin, the opioid antagonist naltrexone and the serotonine reuptake inhibitor sertraline are recommended by evidence-based guidelines as stepwise therapeutic approaches to treat itch in cholestasis. Rifampicin, the most effective antipruritic agent in cholestatic itch, has been shown to reduce autotaxin transcription in vitro. Experimental approaches include UVB phototherapy, extracorporeal albumin dialysis, nasobiliary drainage and in desperate cases even liver transplantation. Relevant clinical observations along with the different metabolic, neurologic and endocrine targets of available therapies in cholestatic pruritus are reviewed here.

Topics: Anion Exchange Resins; Antipruritics; Cholestasis; Cholestyramine Resin; Combined Modality Therapy; Dialysis; Disease Management; Enzyme Inhibitors; Humans; Narcotic Antagonists; Phosphoric Diester Hydrolases; Phototherapy; Prognosis; Pruritus; Rifampin; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Treatment Outcome

Pruritus can occur as a severe complication of cholestasis. Several hypotheses suggest an important role for the accumulation of bile acids, endogenous opioids and - mire recently - lysophosphatidic acid. Bile acid sequestrants are the first-line therapeutic agents. In refractory cases, a stepwise approach using rifampicin, oral opiate antagonists and the selective serotonin reuptake inhibitor sertraline should be tested. Recent case series reported effective relief of pruritus using extracorporal liver support systems and plasmapheresis.

Topics: Cholestasis; Cholestyramine Resin; Humans; Lysophospholipids; Opioid Peptides; Plasmapheresis; Pruritus; Renal Dialysis; Rifampin; Sertraline; Sorption Detoxification; Ursodeoxycholic Acid

Pruritus is commonly associated with cholestatic disorders and shows wide interindividual variability. The presence of skin lesions due to scratching and the application of a visual analogue scale are useful for clinical evaluation. Although the pathophysiology of this entity is not well understood, advances have recently been made in understanding of the pruritoceptive neural pathway, which shares certain similarities with the nociceptive pathway, although there are other distinguishing characteristics such as the action of a specific neurotransmitter, GPR, on the first synapsis at the posterior horn of the spinal cord. Amongst the modulator systems of the pruritoceptive pathway is the action of the endogenous opioids. An increase of these opioids in cholestatic situations is the most widely accepted hypothesis for pruritus in these patients. Some treatments have proven efficacy in randomized clinical trials in patients with cholestatic disorders, such as anion exchange resins, rifampicin, opioid antagonists and ursodeoxycholic acid; the latter is especially useful in intrahepatic cholestasis of pregnancy.

Topics: Animals; Anion Exchange Resins; Cholestasis; Evidence-Based Medicine; Female; Gastrin-Releasing Peptide; Haplorhini; Humans; Male; Models, Neurological; Narcotic Antagonists; Neural Pathways; Opioid Peptides; Posterior Horn Cells; Pregnancy; Pregnancy Complications; Pruritus; Randomized Controlled Trials as Topic; Rifampin; Ursodeoxycholic Acid

The objective of this review was to evaluate the efficacy and safety of rifampin, opioid antagonists, or bile acid binding agents in the treatment of cholestasis-related pruritus (CAP) from available randomized controlled trial evidence.. In addition to a comprehensive gray literature search, the Cochrane Library, MEDLINE, EMBASE, PubMed, and Web of Science were searched. Only full-text RCTs in participants (>75% adult) with CAP on at least one of the three medications were included. The primary outcome was change in pruritus score, recorded as a continuous or dichotomous outcome. Two independent reviewers performed trial selection and quality assessment.. From 487 citations, 12 RCTs were included. Rifampin (standardized mean difference [SMD]-1.62, 95% CI -3.05 to -0.18) and opioid antagonists (SMD -0.68, 95% CI -1.19 to -0.17) significantly reduced CAP. The two cholestyramine studies were too heterogeneous to pool. Although cholestyramine (P= 0.35) and rifampin (P= 0.96) were not associated with greater side effects compared with placebo, opioid antagonists were (number needed to harm = 2.6, 95% CI 1.4-25).. The available RCTs are small, few in number, and use varying scales for measuring pruritus. Although both opioid antagonists and rifampin demonstrated a reduction in pruritus, there were insufficient data to judge the efficacy of cholestyramine. Opioid antagonists were associated with transient side effects in a significant proportion of patients. A longer well-designed randomized controlled trial is needed to confirm the efficacy of bile acid binding agents and accurately assess adverse events.

Topics: Anticholesteremic Agents; Cholestasis; Cholestyramine Resin; Humans; Leprostatic Agents; Narcotic Antagonists; Pruritus; Randomized Controlled Trials as Topic; Rifampin; Treatment Outcome

The treatment of cholestatic pruritus in children is reviewed.. Cholestasis is characterized by an accumulation of substances that are normally secreted in the bile. Pruritus is a well-known feature of chronic cholestasis in both adults and children and has been reported as the most incapacitating symptom in children with chronic liver disease. Traditional agents, such as antihistamines, are typically ineffective as monotherapy in controlling cholestatic pruritus. As a result, clinicians have looked to other agents, such as rifampin, phenobarbital, ursodiol, opioid antagonists, and bile-binding resins, for attaining better control of pruritic symptoms. Each agent demonstrates different levels of efficacy in pediatric and adult literature. There are no guidelines or algorithms to guide therapy with these agents for children. As a result, an agent should be selected based on the patient's concurrent diseases and current medication regimen. Cholestyramine and ursodiol are both safe and inexpensive, with documented efficacy for cholestatic pruritus in children. Because cholestatic pruritus is likely a result of multiple mechanisms, combination therapy with agents that have differing mechanisms of action might be beneficial and could capitalize on potential synergy between the agents used. Future therapy for cholestatic pruritus may include serotonin antagonists, selective serotonin-reuptake inhibitors, and leukotriene antagonists.. Depending on the underlying disease state resulting in cholestasis, phenobarbital, ursodiol, bile sequestering agents, and opioid antagonists appear to be most effective for treating pruritus related to intrahepatic cholestasis. Alternatively, rifampin appears to be the only agent with reported treatment efficacy for pruritus related to extrahepatic cholestasis.

Topics: Antipruritics; Child; Cholagogues and Choleretics; Cholestasis, Extrahepatic; Cholestasis, Intrahepatic; Cholestyramine Resin; Histamine H1 Antagonists; Humans; Narcotic Antagonists; Phenobarbital; Pruritus; Rifampin; Ursodeoxycholic Acid

To determine the safety and efficacy of rifampin for treatment of pruritus associated with cholestasis due to chronic liver disease.. Medical literature was searched systematically using keywords as rifampicin, rifampin, rifamycin, cholestasis, pruritus, itching, and liver disease. Trials that compared the efficacy of rifampin with placebo/alternative for treatment of pruritus due to chronic cholestasis were selected for analysis. Primary outcomes were resolution of pruritus and development of side effects. Association was measured with the odds ratio (OR). Breslow-Day method was used to treat for homogeneity under null hypothesis that OR was consistent across all the trials. Corrected Mantel-Haenszel chi(2) test was used to test if OR differed systematically from value of 1.. Five prospective randomized-controlled cross-over trials with 61 patients were identified. Treatment with rifampin led to complete or partial resolution of pruritus in 47 (77%) patients as compared with 12(20%) treated with placebo or alternative (OR 15.2, 95% confidence interval 5.2-45.6, P=0.001). Four (7%) patients treated with rifampin suffered side effects, which resolved after its discontinuation. There was no incidence of hepatotoxicity. Test of heterogeneity for primary end points among the trials was not significant (P=0.16).. This meta-analysis suggests that rifampin is safe and effective for treatment of pruritus due to chronic cholestasis. This analysis also suggests that use of rifampin for short duration is associated with a low risk of hepatotoxicity.

Topics: Cholestasis; Chronic Disease; Cross-Over Studies; Humans; Prospective Studies; Pruritus; Rifampin

Pruritus is often the most troublesome symptom in patients with chronic liver disease, particularly when cholestasis is a prominent feature. The exact pathogenesis is unknown, but empirical treatment, such as cholestyramine, based on a liver-based origin of pruritus, has been used for many years. Recently, evidence for a central mechanism for pruritus has been obtained and opioid antagonists have been tried clinically with some benefit, but their use is not widespread. In addition, the pruritus associated with intrahepatic cholestasis of pregnancy can now be alleviated in many cases by ursodeoxycholic acid. As it also improves foetal outcome, this should become first-line therapy. We review the pathogenesis and therapy of pruritus, highlighting practical aspects to help with patients with seemingly intractable pruritus.

Topics: Anion Exchange Resins; Antipruritics; Cholagogues and Choleretics; Humans; Liver Diseases; Narcotic Antagonists; Ondansetron; Pruritus; Rifampin; Ursodeoxycholic Acid

Pruritus is a frequent, distressing and sometimes disabling symptom of liver and biliary tract disorders. Results of treatment are sometimes disappointing and the pathophysiology is still largely unknown. It was recently discovered that endogenous opioids contribute to the perception of itching and that opiate receptor antagonists can reduce the overstimulation of these receptors and thereby attenuate the itching. A stepwise treatment strategy focusing successively on ion exchange resins, rifampicin and opiate receptor antagonists leads to effective alleviation of itching in most patients.

Topics: Cholestasis; Histamine H1 Antagonists; Humans; Ion Exchange Resins; Narcotic Antagonists; Pruritus; Receptors, Opioid; Rifampin; Serotonin Antagonists; Ultraviolet Therapy

Topics: Androgens; Antipruritics; Bile Acids and Salts; Cholestasis; Cholestyramine Resin; Female; Humans; Narcotic Antagonists; Plasmapheresis; Pregnancy; Pregnancy Complications; Propofol; Pruritus; Rifampin; Ultraviolet Therapy; Ursodeoxycholic Acid

Topics: Histamine H1 Antagonists; Humans; Pruritus; PUVA Therapy; Rifampin; Ultraviolet Therapy

Pruritus is one of the most common and disabling symptoms of liver disease such as Primary Sclerosing Cholangitis and Primary Biliary Cholangitis. Cholestyramine, rifampin, opioid antagonists, antihistaminic agents and SSRIs are used for the management of pruritus. Due to rifampin drug interactions as well as its serious side effects such as hepatotoxicity, clinicians are endeavoruing to find a safer and a more effective substitution.. The purpose of this study was to compare the efficacy and safety of sertraline with rifampin in the management of cholestatic pruritus.. In a single-blinded randomized clinical trial a total of 36 patients of PSC and PBC were divided into two equal groups, one group received 100 mg/day sertraline and the other group received rifampin 300 mg/day for 4 weeks. Visual analog scale was used to record pruritus severity at baseline and 4 weeks after drug intervention, also, ALT, AST, ALP and total bilirubin of all patients were measured at three different time points.. Over the follow-up period, pruritus had relieved in both groups, but there was no significant differences between sertraline and rifampin in pruritus management (pvalue=0.740), also there was no significant difference between the two intervention strategies (A versus B) in total bilirubin level (pvalue=0.106). Moreover, the ALT, AST and ALP levels were found to be significantly different between the two groups (Pvalue˂0.01).. There is no difference between sertraline and rifampin in pruritus improvement, but sertraline has less adverse effects on hepatobiliary enzyme levels, so it seems to be safer than rifampin.

Topics: Adult; Anti-Bacterial Agents; Cholestasis; Female; Humans; Male; Middle Aged; Pruritus; Rifampin; Selective Serotonin Reuptake Inhibitors; Sertraline; Single-Blind Method; Treatment Outcome

To determine the safety and efficacy of rifampin for treatment of pruritus associated with cholestasis due to chronic liver disease.. Medical literature was searched systematically using keywords as rifampicin, rifampin, rifamycin, cholestasis, pruritus, itching, and liver disease. Trials that compared the efficacy of rifampin with placebo/alternative for treatment of pruritus due to chronic cholestasis were selected for analysis. Primary outcomes were resolution of pruritus and development of side effects. Association was measured with the odds ratio (OR). Breslow-Day method was used to treat for homogeneity under null hypothesis that OR was consistent across all the trials. Corrected Mantel-Haenszel chi(2) test was used to test if OR differed systematically from value of 1.. Five prospective randomized-controlled cross-over trials with 61 patients were identified. Treatment with rifampin led to complete or partial resolution of pruritus in 47 (77%) patients as compared with 12(20%) treated with placebo or alternative (OR 15.2, 95% confidence interval 5.2-45.6, P=0.001). Four (7%) patients treated with rifampin suffered side effects, which resolved after its discontinuation. There was no incidence of hepatotoxicity. Test of heterogeneity for primary end points among the trials was not significant (P=0.16).. This meta-analysis suggests that rifampin is safe and effective for treatment of pruritus due to chronic cholestasis. This analysis also suggests that use of rifampin for short duration is associated with a low risk of hepatotoxicity.

Topics: Cholestasis; Chronic Disease; Cross-Over Studies; Humans; Prospective Studies; Pruritus; Rifampin

The natural history of pruritus in primary biliary cirrhosis (PBC) remains poorly defined. The aim of this investigation was to evaluate outcomes of pruritus in clinical trials for ursodeoxycholic acid (UDCA). In a UDCA-placebo trial begun in 1988 (n = 180), a 55% prevalence rate for pruritus was observed. Serum alkaline phosphatase level and Mayo risk score were independent risk factors for pruritus (P < 0.0001). Among placebo-treated patients (n = 91), the annual risks for development or improvement/resolution of pruritus were 27% and 23%, respectively. For UDCA-treated patients (n = 89), a trend toward improvement in pruritus was observed after 1 year compared to placebo (30% vs. 23%, P = 0.08) but not at 2 or 3 years. In a 3-dose UDCA trial begun in 1995 (n = 155), the overall prevalence of pruritus was significantly lower at 37% when compared to UDCA-placebo participants (P < 0.001). Baseline serum alkaline phosphatase level and Mayo risk score were again independent risk factors for pruritus (P < 0.0001). Among 13 (3.9%) patients with refractory pruritus, symptom resolution (n = 5) or improvement (n = 8) was associated with the use of oral rifampin (300 or 600 mg daily). Two patients treated with rifampin developed biochemical evidence for hepatotoxicity necessitating drug withdrawal. Although less prevalent among recently diagnosed individuals, more than one third of PBC patients develop pruritus. No significant risk reduction in developing pruritus with UDCA therapy was observed compared to placebo-treated patients. The long-term administration of rifampin for refractory pruritus is associated with occasional hepatotoxicity.

Topics: Adult; Alkaline Phosphatase; Antipruritics; Aspartate Aminotransferases; Bilirubin; Biomarkers; Cholagogues and Choleretics; Cholestyramine Resin; Dose-Response Relationship, Drug; Double-Blind Method; Enzyme Inhibitors; Female; Follow-Up Studies; Humans; Incidence; Liver Cirrhosis, Biliary; Liver Function Tests; Male; Middle Aged; Minnesota; Multivariate Analysis; Predictive Value of Tests; Pruritus; Rifampin; Risk Factors; Serum Albumin; Severity of Illness Index; Treatment Outcome; Ursodeoxycholic Acid

Rifampin has been proposed to reduce pruritus in children and adults with chronic cholestasis; however, there is a paucity of published data regarding the use of rifampin in children.. In an open trial, 24 children were evaluated during a 6-year period. Diagnoses included 13 patients with extrahepatic biliary atresia (54%), six with Alagille's syndrome, three with Byler's disease, and one each with primary sclerosing cholangitis and alpha1-antitrypsin deficiency. All patients had severe pruritus that had not responded adequately to at least 2 months of therapy with ursodeoxycholic acid, diphenhydramine, or phenobarbital and local skin care measures. Treatment was initiated with rifampin, 10 mg/kg per day in two divided doses for 18+/-20 months, and the effect on the severity of pruritus was assessed by a clinical scoring system.. Ten patients showed a complete response, 12 a partial response, and 2 no response. Complete response was more common in extrahepatic cholestasis (64% vs. 10%), whereas partial response was more common in intrahepatic cholestasis (80% vs. 29%). Treatment was associated with reduction of gamma-glutamyl transpeptidase. No clinical or biochemical toxicity of rifampin was observed.. We conclude that for more than 90% of children with chronic cholestasis and severe pruritus unresponsive to other treatments, rifampin appears to be a safe and effective therapy.

Topics: Adolescent; Child; Child, Preschool; Cholestasis; Chronic Disease; Female; Humans; Infant; Male; Pruritus; Rifampin; Treatment Outcome

The effects of rifampicin treatment (10 mg.kg-1.day-1) on pruritus and cholestasis were evaluated in 16 patients with primary biliary cirrhosis and pruritus followed up for 2-24 months. Assessment of pruritus severity, liver tests, aminopyrine breath test, and bile acids was done at 2 weeks and every 3 months after the beginning of the study. Two patients (12.5%) were withdrawn after 2 months of treatment because they had hepatitis caused by rifampicin. Four patients were withdrawn after 4 months because of liver transplantation (3 cases) and the development of leg edema associated with administration of rifampicin. The remaining 10 patients received therapy for 14.4 +/- 0.7 months and did not experience side effects. Pruritus improved in all patients and disappeared in 11 patients (79%) after 3 months of treatment. Moreover, all patients followed up for more than 1 year were free of pruritus. The alkaline phosphatase level decreased significantly, and the aminopyrine breath test results increased significantly after 2 weeks of treatment (P less than 0.001) and did not change thereafter. In the 9 patients treated for 15 months, alkaline phosphatase levels decreased to 63% of the basal levels and aminopyrine breath test results increased to 153% of baseline values. Transaminases, gamma-glutamyltransferase, and total bile salt levels decreased significantly after 2 weeks of treatment but returned to baseline after 3 months. No changes in bilirubin and cholesterol levels were observed. It is concluded that long-term rifampicin treatment is effective for relieving pruritus in primary biliary cirrhosis, but liver enzymes should be monitored to detect drug-induced hepatitis.

Topics: Bile Acids and Salts; Cholestasis; Female; Humans; Liver; Liver Cirrhosis, Biliary; Middle Aged; Pruritus; Rifampin

Pruritus can be a debilitating symptom in patients with chronic cholestasis. Based on previous reports of its efficacy, we evaluated the impact of rifampin on the pruritus associated with primary biliary cirrhosis. Fourteen patients were included in a randomized, crossover study. After a 15-day washout period, subjects were followed for three weeks. During the first and third week, patients received 600 mg of rifampin or placebo; no treatment was administered during the second week. Pruritus was subjectively scored on a scale from 0 to 100. With rifampin, pruritus disappeared in 11 patients and partially improved in three; with placebo, only two had a partial response (P less than 0.001). Six patients with a prior poor or no response to cholestyramine improved with rifampin. No changes in biochemical tests or side effects were observed during this period. We conclude that short-term administration of rifampin relieves pruritus in primary biliary cirrhosis. When administered over a period of eight months in an open study, the relief of pruritus was maintained, while one individual developed an allergic reaction. Rifampin appears to be a safe drug in the management of the pruritus of primary biliary cirrhosis.

Topics: Adult; Aged; Alkaline Phosphatase; Bilirubin; Female; Humans; Liver Cirrhosis, Biliary; Male; Middle Aged; Pruritus; Rifampin

Chronic cholestatic liver disease in children frequently results in severe intractable pruritus. Current forms of therapy, including cholestyramine, are usually ineffective. Therefore, a 6-wk, double-blind, crossover study was designed to test the ability of rifampin to relieve pruritus in children with chronic cholestasis. Rifampin proved effective in alleviating pruritus in all five children tested compared with a placebo-treated group. After the 6-wk study period, rifampin was continued for 6 mo, and its effectiveness was maintained. No complications resulted from rifampin use. This study and a similar study in older patients with primary biliary cirrhosis suggest that a highly effective form of therapy is available for treatment of severe pruritus in patients with chronic cholestasis. These patients must be carefully selected and frequently monitored.

Topics: Adolescent; Child; Cholestasis, Intrahepatic; Chronic Disease; Double-Blind Method; Humans; Pruritus; Randomized Controlled Trials as Topic; Rifampin

We investigated the effect of rifampin on pruritus in 12 patients with chronic liver disease: non-A, non-B hepatitis (n = 3), alcoholic cirrhosis (n = 4), primary biliary cirrhosis (n = 4), and primary sclerosing cholangitis (n = 1). The study was a crossover, randomized, double-blind trial where placebo and drug were given daily in identical capsules (300 mg) for 2 weeks each, with a 1 week washout before and after each cycle. Mean duration of pruritus was 1.6 years (range of 4 months-5 years). Blood tests were done weekly and patients used a visual analogue scale (VAS) from 0 to 100 to mark their level of itchiness daily. Only transaminases were significantly lower while the patients were on rifampin. VAS scores were minimally affected by either rifampin or placebo. At the end of the trial, four patients said they were less itchy on rifampin and three preferred placebo. Of these seven patients, small falls in VAS scores occurred in two patients on rifampin and two on placebo; there was no change in the remaining three. There was little change in serum bile salt levels during the trial. No patient became jaundiced and deepening of jaundice did not occur in the four patients with initially elevated bilirubin. We conclude that a daily 300 mg dose of rifampin was not effective in relieving pruritus in a variety of chronic liver diseases.

Topics: Adult; Aged; Chronic Disease; Double-Blind Method; Female; Humans; Liver Diseases; Male; Middle Aged; Monitoring, Physiologic; Pruritus; Randomized Controlled Trials as Topic; Rifampin

The anti-pruritic effects of rifampicin (10 mg/kg) and phenobarbitone (3 mg/kg) were assessed in 22 patients with primary biliary cirrhosis in a crossover randomised clinical trial. Each agent was given for 14 days, with a 30-day washout period between treatments. 21 patients completed the course of rifampicin and 18 that of phenobarbitone; rifampicin was withdrawn from 1 patient when anaemia and renal failure developed, whereas 3 patients stopped taking phenobarbitone because of a rash and the 4th merely refused the drug. Rifampicin had a greater anti-pruritic effect than phenobarbitone. The symptom improved in 19 patients taking rifampicin and in 8 taking phenobarbitone, the degree of improvement being greater with rifampicin than with phenobarbitone. Pruritus disappeared in 9 patients receiving rifampicin, and three of them were free of itch when switching over to phenobarbitone. Both drugs were equally effective in inducing hepatic microsomal function but rifampicin has the additional effect of reducing cholestasis. Its anti-pruritic effect should be tested in long-term clinical trials.

Topics: Adult; Cholestasis; Clinical Trials as Topic; Drug Administration Schedule; Female; Humans; Liver Cirrhosis, Biliary; Microsomes, Liver; Middle Aged; Phenobarbital; Pruritus; Random Allocation; Rifampin; Severity of Illness Index

The cause of pruritus of cholestasis is unknown. We have hypothesized that pruritus may be caused by an indirect effect of high hepatic concentrations of toxic bile acids. To test this hypothesis, we have conducted a double-blind, controlled, crossover clinical trial of rifampin, an agent that inhibits hepatic bile acid uptake and may detoxify hepatic bile acids by stimulation of mixed-function oxidases. Nine patients with primary biliary cirrhosis received 300-450 mg/day of rifampin and placebo sequentially, in random order. Each treatment was administered for 14 days, with a 14-day washout between treatments. Endpoints included patient preference, changes in a daily visual analogue scale pruritus score, and amount of cholestyramine ingested. Antipyrine elimination rates and serum bile acids were tested at the end of each treatment period. All 9 patients completed the trial and 8 of them preferred rifampin to placebo (p = 0.03). There were no adverse reactions. Visual analogue scale pruritus scores showed no significant placebo response or any effect from the order of treatment, but did show a highly significant reduction in pruritus in response to rifampin (p less than 0.002). This effect was evident within the first week of rifampin treatment. Rifampin produced a 33% reduction in antipyrine plasma half-life, but no change in fasting total serum bile acids. Cholestyramine usage did not change significantly. We conclude that rifampin is useful for short-term relief of pruritus in primary biliary cirrhosis; however, the mechanism of this effect is unknown. Longer trials are needed, as are trials in other cholestatic disorders.

Topics: Antipyrine; Bile Acids and Salts; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Liver Cirrhosis, Biliary; Middle Aged; Placebos; Pruritus; Random Allocation; Rifampin

Maintenance dialysis patients are at an increased risk for active tuberculosis (TB). In 2012, British Columbia, Canada, began systematically screening maintenance dialysis patients for latent TB infection (LTBI) and treating people with evidence of LTBI when appropriate. We examined LTBI treatment outcomes and compared treatment outcomes before and after rollout of the systematic screening program.. Retrospective cohort study.. The study comprised 365 people in British Columbia, Canada, initiating at least 90 days of dialysis from January 1, 2001, to May 31, 2017, and starting LTBI therapy: 290 (79.5%) people in the recent cohort and 75 (20.5%) in the historical cohort. People starting LTBI therapy from January 1, 2012, onward were classified as the recent cohort, whereas people starting LTBI therapy before January 1, 2012, were classified as the historical cohort.. Systematic LTBI screening and therapy.. Proportion of people who experience grade 3 to 5 adverse events (AEs) or any grade rash and end-of-treatment outcomes.. Outcomes were reported using descriptive statistics. 2-sample test of proportions using χ. 298 (81.6%) people successfully completed LTBI therapy. The proportion of people experiencing a grade 3 to 4 AE or any grade rash was 21.1%. Most AEs were related to gastrointestinal events, general malaise, or pruritus that resulted in regimen changes. 2 (0.5%) people were hospitalized for AEs related to LTBI therapy. No significant difference was found between the recent and historical cohorts in all outcomes of interest. No grade 5 AEs (deaths) were attributed to LTBI therapy.. Retrospective data and generalizability outside low-TB-burden settings.. Our findings suggest that a high proportion of people receiving maintenance dialysis can complete LTBI therapy. The rate of grade 3 to 4 AEs was high and associated with frequent medication changes during therapy. LTBI therapy in maintenance dialysis may be safe but requires close monitoring.

Topics: Aged; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Cohort Studies; Exanthema; Female; Gastrointestinal Diseases; Humans; Isoniazid; Kidney Failure, Chronic; Latent Tuberculosis; Male; Mass Screening; Middle Aged; Pruritus; Renal Dialysis; Retrospective Studies; Rifabutin; Rifampin; Treatment Outcome; Vitamin B 6

The use of rifampicin for cholestatic pruritus is accompanied by concerns over safety, but the availability of real-world prescribing data is relatively limited.. We sought to describe the rate and characteristics of rifampicin-induced hepatitis in a mixed aetiology cohort of patients with established liver disease and cholestatic pruritus.. Retrospective review of records for out-patients commenced on rifampicin for pruritus 2012-2016 inclusive. Rifampicin-induced hepatitis was recorded where alanine aminotransferase activity (ALT) increased to both ≥5 × baseline and ≥5 × upper limit of normal (ULN), or to both ≥3 × baseline and ≥3 × ULN with concurrent elevation in serum bilirubin to ≥2 × baseline and ≥2 × ULN, in addition to a Roussel-Uclaf Causality Assessment Method score of "probable" or "highly probable" for rifampicin causality.. After exclusions, we reviewed 105 patients who took rifampicin for a median of 131 days. Most had primary biliary cholangitis or primary sclerosing cholangitis; 40 (38.1%) were men and median age was 44 years (IQR: 32-57). 44 (41.9%) patients had baseline serum bilirubin ≥2 × ULN and 28 (26.7%) ALT ≥3 × ULN. 5 (4.8%) developed rifampicin-induced hepatitis at a median of 70(range 27-130) days after drug initiation. No individual or laboratory baseline characteristics were significantly associated with subsequent development of hepatitis. All cases of hepatitis recovered after drug cessation, although one patient was hospitalised and received corticosteroids.. Given the efficacy of rifampicin for an important sub-group of those with cholestatic pruritus, adult patients, including those with jaundice, can be counselled that 95% of prescriptions are safe, and where hepatitis occurs, including at long latency, drug cessation appears effective.

Topics: Adult; Cholestasis; Cohort Studies; Female; Humans; Liver Diseases; Male; Middle Aged; Pruritus; Rifampin; Risk Factors

Topics: Chemical and Drug Induced Liver Injury; Cholestasis; Cohort Studies; Humans; Pruritus; Rifampin

In vitro studies have suggested that 4-phenylbutyrate (PBA) may rescue missense mutated proteins that underlie some forms of progressive familial intrahepatic cholestasis. Encouraging preliminary responses to 4-PBA have been reported in liver disease secondary to mutations in ABCB11 and ATP8B1. A 4-year-old boy with Byler disease was treated with 4-PBA in the forms of sodium PBA (5 months) and then glycerol PBA (7 months) as part of expanded access single patient protocols. During this therapy serum total bilirubin fell and his general well-being was reported to be improved, although total serum bile acids were not reduced. Discontinuation of rifampin therapy, which had been used to treat pruritus, resulted in reversible severe acute liver injury that was potentially the result of phenylacetate toxicity. Interactions between 4-PBA and cytochrome P450 enzymes should be considered in the use of this agent with special attention to potential phenylacetate toxicity.

Topics: Antineoplastic Agents; Bilirubin; Chemical and Drug Induced Liver Injury; Child, Preschool; Cholestasis, Intrahepatic; Humans; Infant; Liver; Liver Function Tests; Male; Phenylacetates; Phenylbutyrates; Pruritus; Rifampin

Topics: Alkaline Phosphatase; Anticholesteremic Agents; Cholestasis; Cholestyramine Resin; Female; Humans; Liver; Liver Diseases; Liver Function Tests; Male; Practice Guidelines as Topic; Primary Health Care; Pruritus; Rifampin

Alagille syndrome (AGS) is an autosomal dominant disorder of chronic cholestasis characterized by paucity of interlobular bile ducts. The condition has been described only as isolated case reports in India. We describe clinical profile and outcome of nine subjects (six infants and three older children) with AGS. Cholestasis and characteristic facies were present in all, followed by congenital heart disease, vertebral anomalies, and posterior embryotoxon in seven, five, and four cases, respectively. Pruritus was the commonest symptom which was refractory to medical treatment in one third of cases. Two cases developed decompensated liver disease on follow up. High index of suspicion for this multisystemic condition is essential for correct diagnosis and management.

Topics: Alagille Syndrome; Calcium, Dietary; Child; Child, Preschool; Cholagogues and Choleretics; Cholestasis; Cholestyramine Resin; Energy Intake; Female; Humans; India; Infant; Male; Prognosis; Pruritus; Recommended Dietary Allowances; Rifampin; Tertiary Care Centers; Triglycerides; Ursodeoxycholic Acid; Vitamins

Topics: Aged; Antibiotics, Antitubercular; Drug Eruptions; Humans; Lichenoid Eruptions; Male; Pruritus; Rifampin; Tuberculosis, Pulmonary

Topics: Aged; Antibiotics, Antitubercular; Blood Coagulation Disorders; Cholangitis, Sclerosing; Female; Humans; Male; Middle Aged; Pruritus; Rifampin; Risk Factors

Pruritus is a seriously disabling symptom accompanying many cholestatic liver disorders. Recent experimental evidence implicated the lysophospholipase, autotaxin (ATX), and its product, lysophosphatidic acid (LPA), as potential mediators of cholestatic pruritus. In this study, we highlight that increased serum ATX levels are specific for pruritus of cholestasis, but not pruritus of uremia, Hodgkin's disease, or atopic dermatitis. Treatment of patients with cholestasis with the bile salt sequestrant, colesevelam, but not placebo, effectively reduced total serum bile salts and fibroblast growth factor 19 levels, but only marginally altered pruritus intensity and ATX activity. Rifampicin (RMP) significantly reduced itch intensity and ATX activity in patients with pruritus not responding to bile salt sequestrants. In vitro, RMP inhibited ATX expression in human HepG2 hepatoma cells and hepatoma cells overexpressing the pregnane X receptor (PXR), but not in hepatoma cells in which PXR was knocked down. Treatment of severe, refractory pruritus by the molecular adsorbents recirculation system or nasobiliary drainage improved itch intensity, which, again, correlated with the reduction of ATX levels. Upon reoccurrence of pruritus, ATX activity returned to pretreatment values.. Serum ATX activity is specifically increased in patients with cholestatic, but not other forms of, systemic pruritus and closely correlates with the effectiveness of therapeutic interventions. The beneficial antipruritic action of RMP may be explained, at least partly, by the PXR-dependent transcriptional inhibition of ATX expression. Thus, ATX likely represents a novel therapeutic target for pruritus of cholestasis.

Topics: Allylamine; Analysis of Variance; Antipruritics; Biomarkers; Blotting, Western; Carcinoma, Hepatocellular; Case-Control Studies; Cholestasis; Cohort Studies; Colesevelam Hydrochloride; Electrophoresis, Polyacrylamide Gel; Female; Fibroblast Growth Factors; Hep G2 Cells; Humans; Liver Neoplasms; Lysophospholipase; Male; Multivariate Analysis; Phosphoric Diester Hydrolases; Polymerase Chain Reaction; Pruritus; Rifampin; ROC Curve; Treatment Outcome

Pruritus is a common symptom of hepatobiliary disorders and may considerably diminish quality of life. Cholestatic pruritus exerts a circadian rhythm and is typically most severe in the evening hours and early at night. Itching is reported often to be most intense at the palms and the soles, but may also be generalized. The pathophysiological mechanisms of cholestatic pruritus have not been completely clarified. In the past, bile salts, histamine, progesterone metabolites and opioids have been discussed as potential causal substances; a correlation with itch intensity could never be proven. The enzyme autotaxin, which releases lysophosphatidic acid, has recently been identified as potential cholestatic pruritogen. Treatment aims to bind pruritogens in the gut lumen by resins such as cholestyramine, to modulate pruritogen metabolism by rifampicin and to influence central itch signaling by µ-opioid antagonists and selective serotonin re-uptake inhibitors. In cases of refractory pruritus experimental treatment options such as UV-therapy, extracorporeal albumin dialysis and nasobiliary drainage may be considered.

Topics: Cholestasis; Humans; Narcotic Antagonists; Pruritus; Rifampin; Serotonin Antagonists

Topics: Adult; Antitubercular Agents; Drug Combinations; Drug Eruptions; Drug Therapy, Combination; Dysgeusia; Flushing; Histamine H1 Antagonists; Humans; Isoniazid; Loratadine; Male; Pruritus; Pyrazinamide; Recurrence; Rifampin; Tryptases; Tuberculosis, Pulmonary; Vasodilation

Topics: Adult; Antibiotics, Antitubercular; Anticonvulsants; Antitubercular Agents; Erythema; Ethambutol; Exanthema; Female; Humans; Phenobarbital; Phenytoin; Pruritus; Rifampin

The present study aimed at verifying the safety and efficacy of rifampicin in ameliorating pruritus in cholestatic children.. Twenty-three Egyptian children (14 boys and 9 girls), suffering from intractable pruritus of cholestasis, were included. Rifampicin was started at a dose of 10 mg/Kg/day in two divided doses and increased gradually to a maximum of 20 mg/Kg/day if there was no response. Liver function tests were followed up weekly.. Seventeen patients (74%) showed improvement of pruritus with rifampicin. None of the patients showed any deterioration in liver functions.. Rifampicin in a dose of 10-20 mg/Kg/day is safe and effective in ameliorating uncontrollable pruritus in children with persistent cholestasis.

Topics: Adolescent; Child; Child, Preschool; Cholestasis; Female; Humans; Infant; Male; Pruritus; Rifampin

Ursodeoxycholic acid is widely used as the standard therapy for the treatment of primary biliary cirrhosis and other cholestatic liver diseases. Although it has been shown to improve biochemical markers and delay disease progression, its effect upon fatigue and pruritus, is at best uncertain.. To assess the safety and efficacy of methotrexate for treating symptomatic primary biliary cirrhosis patients who were biochemical partial responders or non-responders to ursodeoxycholic acid therapy.. We treated eight consecutive primary biliary cirrhosis patients with methotrexate who were followed in a single hepatology clinical practice, who were symptomatic, and who had had an incomplete biochemical response to ursodeoxycholic acid therapy. Pruritus and fatigue were assessed at each clinic visit and graded from 0 (asymptomatic) to 4 (incapacitating).. The median dose of methotrexate was 13.75 mg/week (range 7.5-15) and the mean duration of methotrexate therapy was 49 months (range 11-126). At the end of follow-up pruritus in six of seven patients had improved, and fatigue in all patients had improved with the addition of methotrexate therapy (pruritus: baseline 2.9 +/- 1.1 vs. end of treatment 0.6 +/- 1.5, P < or = 0.0175, and fatigue: baseline 3.0 +/- 0.8, vs. end of treatment 1.0 +/- 0.8, P < or = 0.0023). Improvement in symptoms was associated with a significant improvement in biochemical markers of cholestasis. No significant adverse effects of methotrexate were documented.. Methotrexate should be considered as a potential additive treatment for symptomatic primary biliary cirrhosis patients who are incomplete biochemical responders to ursodeoxycholic acid therapy.

Topics: Adult; Alanine Transaminase; Alkaline Phosphatase; Cholagogues and Choleretics; Drug Administration Schedule; Enzyme Inhibitors; Fatigue; Female; gamma-Glutamyltransferase; Humans; Immunosuppressive Agents; Liver Cirrhosis, Biliary; Methotrexate; Middle Aged; Pruritus; Rifampin; Treatment Outcome; Ursodeoxycholic Acid

The pathogenesis of initiating the pruritus in patients with cholestasis is still not completely understood. One hypothesis is, that the cause for initiating the pruritus in patients with cholestasis is the activation of nerves in the skin. The activating substances are unknown, probably they are substances who accumulate in patients with cholestasis. Therefore one of the conventional approaches to treat pruritus is to remove pruritogenic substances from the body. Examples of this approach include the administration of anion exchange resins as cholestyramine or the administration of hepatic enzyme-inducing drugs such as rifampicin or phenobarbital. None of these drugs has been conclusively shown to be efficacious. A new hypothesis is the association of pruritus with altered central neurotransmission. Altered opioid concentrations probably play a central role in the pathogenesis of pruritus. This hypothesis is corroborate by the possibility of treating pruritus in patients with cholestasis with opiate antagonists such as naloxone or nalmefene. The treatment with ondansetron may also have effects on the pruritus of patients with cholestasis. A completely new treatment strategy is the application of dronabinol (r-9-tetrahydrocannabinol).

Topics: Brain; Cholestasis; Cholestyramine Resin; Dronabinol; Enzyme Induction; Humans; Liver; Narcotic Antagonists; Ondansetron; Opioid Peptides; Phenobarbital; Pruritus; Rifampin; Skin; Synaptic Transmission; Treatment Outcome

Topics: Alkaline Phosphatase; Antipruritics; Aspartate Aminotransferases; Bilirubin; Biomarkers; Cholagogues and Choleretics; Cholestyramine Resin; Dose-Response Relationship, Drug; Enzyme Inhibitors; History, 21st Century; Humans; Liver Cirrhosis, Biliary; Pruritus; Rifampin; Serum Albumin; Ursodeoxycholic Acid

Topics: Allylamine; Anti-Bacterial Agents; Bile Acids and Salts; Cholagogues and Choleretics; Cholestasis; Colesevelam Hydrochloride; Humans; Pruritus; Rifampin

There is evidence to suggest that rifampicin is an effective second line therapy for controlling pruritus in patients with chronic cholestatic liver disease. It is most widely used as an antipruritic agent in the autoimmune cholestatic liver disease, primary biliary cirrhosis (PBC). Rifampicin has been reported as causing hepatitis in patients being treated for tuberculosis. Most reports of this have been confounded however by the concurrent use of other hepatotoxic antitubercular therapy. Here we report a single centre experience of the use of rifampicin in PBC, and describe three cases of significant hepatitis associated with rifampicin therapy. Two of these patients had significant impairment of liver synthetic function (necessitating liver transplantation in one case). These are the first reports of impaired hepatic synthetic function due to rifampicin monotherapy. Rifampicin caused significant hepatitis in 7.3% (95% confidence interval 2.5-19.4%) of patients treated for cholestatic liver disease in our centre.

Topics: Adult; Antipruritics; Chemical and Drug Induced Liver Injury; Female; Humans; Liver Cirrhosis, Biliary; Middle Aged; Pruritus; Rifampin

Pruritus is prevalent in 5-12% of palliative care patients. Rifampicin has been shown to be useful both as initial treatment and as salvage treatment after failure of other agents to control the pruritus associated with the cholestatic jaundice of malignancy. We report the case of a 65-year-old woman who complained of severe pruritus after morphine treatment. The use of rifampicin 300 mg twice a day by the i.v. route was successful, and after opioid switching it was no longer necessary to maintain rifampicin in the therapeutic regimen. Controlled clinical trials are warranted to confirm this preliminary observation.

Topics: Aged; Analgesics, Opioid; Enzyme Inhibitors; Female; Humans; Morphine; Pain; Pruritus; Rifampin; Treatment Outcome

Topics: Antibiotics, Antitubercular; Cholestasis; Drug Resistance, Microbial; Humans; Immunocompromised Host; Neoplasms; Pruritus; Rifampin

We report 3 cases of rash after the first dose of antituberculosis polytherapy, thus raising questions concerning the procedures to be followed.. Three patients developed a pruritic rash 1 hour after the first dose of isoniazide, rifampicine, pyrazinamide and ethambutol given simultaneously. The eruption did not recur after readministration of isoniazide and rifampicine successively. Pyrazinamide, which was readministered last (at the full dose in one case and at progressive doses in the two others), induced a recurrence in two of them. Pyrazinamide was definitively withdrawn in one patient with recurrence and slower pyrazinamide readministration allowed continuation of treatment in the other two patients.. Since pyrazinamide appeared to be responsible for rash following the first administration of antituberculosis polytherapy, a protocol for readministration of the 4 drugs is suggested. If the responsibility of pyrazinamide is confirmed it should be readministered very slowly.

Topics: Aged; Antitubercular Agents; Child; Drug Combinations; Drug Eruptions; Ethambutol; Exanthema; Female; Humans; Isoniazid; Male; Middle Aged; Pruritus; Pyrazinamide; Recurrence; Rifampin; Tuberculosis, Pulmonary

Topics: Antibiotics, Antitubercular; Child; Cholestasis; Contraindications; Drug Resistance, Microbial; Humans; Pruritus; Rifampin; Tuberculosis

Rifampicin is an effective drug against pruritus in intrahepatic cholestasis. However, there is no specific hepatic disease in which its use could cause undoubtedly biochemical improvement. The aim of this study was to describe patients with complete remission of cholestatic symptoms after rifampicin therapy.. We reported three female patients with intrahepatic cholestasis with no evidence of viral, metabolic, or autoimmune liver diseases. Total bilirubin levels ranged from 13.2 to 27.2 mg/dl (before the first treatment with rifampicin), and in all of them gamma-glutamyl transpeptidase values were within the normal range or slightly increased. Rifampicin therapy was administered orally, without any concomitant drug, with an effective dosage of 5-17 mg/kg/day.. In all patients, pruritus ceased completely and bilirubin returned to normal values. The symptoms recurred after rifampicin withdrawal on, at least, three occasions in each patient, and these symptoms were always eliminated after its reintroduction. The patients had a total of 16 cholestatic episodes during a follow-up of 8 yr, with a complete clinical recovery in all of them. Undergoing therapy with a suitable dosage of rifampicin, none of the patients had a cholestatic crisis even during a period for as long as 12 months. The diagnosis of two patients was consistent with benign recurrent intrahepatic cholestasis, and it was not well defined in the remaining.. Rifampicin may induce clinical remission, and perhaps prevent clinical relapses of intrahepatic cholestasis with normal or slightly increased levels of gamma-glutamyl transpeptidase.

Topics: Adult; Child, Preschool; Cholagogues and Choleretics; Cholestasis, Intrahepatic; Family Health; Female; gamma-Glutamyltransferase; Humans; Pruritus; Recurrence; Remission Induction; Rifampin

The efficacy and safety of using rifampicin to treat the pruritus associated with malignant cholestasis was evaluated. The outcomes of eight patients who received 150 mg rifampicin twice daily were reviewed. All responded, with six having complete resolution of the itch. Two patients were able to discontinue rifampicin following resolution of their cholestatic jaundice by surgery and chemotherapy respectively. No side effects were reported. Rifampicin is a safe effective treatment for the pruritus associated with cholestasis secondary to cancer.

Topics: Adult; Aged; Antipruritics; Cholestasis; Female; Humans; Male; Middle Aged; Palliative Care; Pruritus; Rifampin; Treatment Outcome

Topics: Child, Preschool; Cholestasis, Intrahepatic; Humans; Jaundice; Male; Pruritus; Recurrence; Rifampin; Time Factors

Topics: Antipruritics; Cholestasis; Female; Humans; Infant; Male; Pruritus; Rifampin; Sampling Studies

To report a probable case of moderate pruritus associated with intravenous rifampin.. A 57-year-old woman was started on vancomycin 1 g i.v. q72h following a positive blood culture for methicillin-resistant Staphylococcus epidermidis. The patient's past medical history was significant for uterine carcinoma, radiation-induced enteritis, congestive heart failure, and renal insufficiency. Other therapy consisted of total parenteral nutrition, digoxin 0.125 mg/d i.v., and furosemide 60 mg i.v. prn for edema. Seven days later, the patient's white blood cell count increased and rifampin 600 mg/d i.v. was added to the drug regimen for potential synergy. On day 3 of rifampin therapy, the patient experienced pruritus beginning 30 minutes after the rifampin infusion ended and lasting for 6-8 hours. After 7 days of rifampin therapy, the medication was discontinued and the pruritus resolved.. This case evaluation demonstrated probable pruritus induced by intravenous rifampin. Clinicians should be alerted that intravenous rifampin, as well as orally administered rifampin, has the potential to cause moderate pruritus.

Topics: Female; Humans; Infusions, Intravenous; Middle Aged; Pruritus; Rifampin; Vancomycin

Topics: Aged; Female; Humans; Liver Cirrhosis, Biliary; Prurigo; Pruritus; Rifampin

Pruritus in hepatic cholestasis has been suggested to be secondary to a high concentration of serum bile acids. Rifampicin, which inhibits the uptake of bile acids by hepatocytes, has been used to treat pruritus. To determine the efficacy of rifampicin as a treatment for refractory pruritus, the medical records of 33 children (median age 25 months, range 4-135; 19 boys) with chronic cholestasis liver disease (21 with Alagille's syndrome, eight with progressive intrahepatic cholestasis, one with extrahepatic biliary atresia, one with an inborn error of bile acid metabolism, and one with cryptogenic cirrhosis) were reviewed retrospectively. The median dose of rifampicin was 5(4-10) mg/kg/day. The median duration of intake was 36(4-120) weeks. Complete relief of pruritus was noted in five (15%) patients and a partial response in 12 (36%). Overall, no significant difference was noted in the laboratory parameters before and after treatment with rifampicin. In the 21 patients with Alagille's syndrome, however, a significant decrease in alkaline phosphatase was seen before and after one and six months of starting treatment. No adverse side effects were seen. Rifampicin appears to be effective in the treatment of refractory pruritus. A prospective study is warranted to assess further the effect of rifampicin treatment in children with hepatic cholestasis.

Topics: Child; Child, Preschool; Cholestasis; Female; Humans; Infant; Liver Diseases; Male; Pruritus; Retrospective Studies; Rifampin; Treatment Outcome

Seven patients with primary biliary cirrhosis were treated with rifampicin administered for 2 weeks in a daily dose 450-600 mg. Due to the treatment the itch disappeared completely in 4 and decreased significantly in 3 patients. As shown by the antipyrine test, half-life and clearance of antipyrine returned to normal suggesting cytochrome P-450 induction as a result of hydroxylation activity. There was a tendency to lowering of bilirubin, cholesterol, alkaline phosphatase, asparagine--and alanine aminotransferase against an increase in gammaglobulins. The differences were, however, insignificant. Rifampicin tolerance was satisfactory.

Topics: Adult; Drug Evaluation; Drug Tolerance; Female; Humans; Liver Cirrhosis, Biliary; Middle Aged; Pruritus; Rifampin; Time Factors

Topics: Cholangitis, Sclerosing; Humans; Male; Middle Aged; Pruritus; Rifampin

An acute overdose of rifampicin in an 18 month old white infant is described. The characteristic signs of the syndrome: orange-red discolouration of the skin, urine, and tears, facial pruritus, and periorbital oedema were present and the outcome was uneventful. Paediatricians should be aware of this peculiar yet easily identifiable syndrome.

Topics: Drug Eruptions; Edema; Face; Female; Humans; Infant; Pigmentation Disorders; Pruritus; Rifampin; Syndrome

Topics: Alanine Transaminase; Antitubercular Agents; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Hepatitis A; Humans; Hyperbilirubinemia; Jaundice; Liver Diseases; Pruritus; Rifampin; Tuberculosis