Discontinuation Of Rifampicin Research Articles

The Effect of Rifapentine and Rifampicin on Serum Voriconazole Levels Persist for 5 Days and 7 Days or More After Discontinuation in Tuberculosis Patients with Chronic Pulmonary Aspergillosis.

Voriconazole, a first-line therapeutic agent for chronic pulmonary aspergillosis, is metabolized by the cytochrome 450 enzymes, specifically CYP2C19 and CYP3A4. Rifampicin and rifapentine act as inducers of the cytochrome P450 enzyme. The current study explored the potential drug interactions arising from the co-administration of voriconazole with either rifampicin or rifapentine, as well as the duration of this effect on serum voriconazole levels after discontinuation of rifampicin or rifapentine. A retrospective study was conducted in tuberculosis patients with chronic pulmonary aspergillosis. These patients underwent a combination therapy involving voriconazole and rifampicin or rifapentine, or they were treated with voriconazole after discontinuation of rifampicin or rifapentine. The serum concentrations of voriconazole at steady-state were monitored. Data on demographic characteristics and the serum voriconazole levels were used for statistical analyses. A total of 124 serum voriconazole concentrations from 109 patients were included in the study. The average serum concentration of voriconazole fell below the effective therapeutic range in patients treated with both voriconazole and rifampicin or rifapentine. Notably the co-administration of rifapentine led to a substantial (>70%) decrease in serum voriconazole levels in two patients. Moreover, this interfering effect persisted for at least 7 days following rifampicin discontinuation, while it endured for 5 days or more after discontinuation of rifapentine. Concomitant use of voriconazole and rifampicin or rifapentine should be avoided, and it is not recommended to initiate voriconazole therapy within 5 or 7 days after discontinuation of rifapentine or rifampicin. Therapeutic drug monitoring not only provides a basis for the adjustment of clinical dose, but also serves as a valuable tool for identifying drug interactions.

Evaluation of the impact of rifampicin on the plasma concentration of linezolid in tuberculosis co-infected patients.

Linezolid combined with rifampicin has shown excellent clinical outcomes against infection by multi-resistant Gram-positive bacteria. However, several studies have indicated that rifampicin reduces the plasma concentration of linezolid in patients with severe infection. Linezolid has been recommended for the treatment of patients with multidrug-resistant or extensively drug-resistant tuberculosis. However, studies on the interaction between linezolid and rifampicin in patients suffering from tuberculosis with infection are lacking. We evaluated the interaction between linezolid and rifampicin based on therapeutic drug monitoring (TDM). A retrospective analysis was undertaken for patients with tuberculosis and infection who were treated with linezolid and undergoing TDM. Patients were divided into the linezolid group and linezolid + rifampicin group. Data on demographic characteristics, disease, duration of linezolid therapy, and the plasma concentration of linezolid were used for statistical analyses. Eighty-eight patients with tuberculosis and infection were assessed. Values for the peak (Cmax) and trough (Cmin) concentrations of linezolid in plasma were available for 42 and 46 cases, respectively. Patients in the linezolid group had a significantly higher Cmax [15.76 (8.07-26.06) vs. 13.18 (7.48-23.64) mg/L, p = 0.048] and Cmin [8.38 (3.06-16.53) vs. 4.27 (0.45-10.47), p = 0.005] than those in the linezolid + rifampicin group. The plasma concentration of linezolid increased obviously in two patients after rifampicin discontinuation. However, the total efficiency and prevalence of hematologic adverse reactions were not significantly different in the linezolid group and linezolid + rifampin group. The plasma concentration of linezolid decreased upon combination with rifampicin, suggesting that TDM may aid avoidance of subtherapeutic levels of linezolid upon co-treatment with rifampicin.

Pharmacotherapy in a Multidisciplinary Paediatric Hospital: Polypharmacy and Drug–Drug Interaction Risk Illustrated with a Clinical Case

Nowadays, the problems caused by polypharmacy are recognised and widely discussed in the medical community. Multimorbidity, which is not uncommon in paediatric practice, comes with an increase in the number of prescriptions and necessitates an active search for tools to reduce the potential risk and frequency of adverse drug–drug interactions in paediatric patients.The aim of the study was to use a clinical case to illustrate the need for monitoring, including laboratory monitoring of pharmacokinetic parameters, during concomitant therapy in paediatric practice.Materials and methods: the study consisted in a retrospective analysis of the archived medical records of an 11-year-old child with nephrotic syndrome associated with a concomitant tuberculous process who had been receiving inpatient treatment with immunosuppressants at the Russian Children’s Clinical Hospital from May to July 2018.Results: the prescription of cyclosporine for nephrotic syndrome entailed monitoring of plasma drug levels for potential pharmacokinetic interactions with the medicinal products used to treat the concomitant disease. The monitoring revealed an interaction between cyclosporine and rifampicin at the level of biotransformation. An adjustment of the concomitant therapy (discontinuation of rifampicin) allowed for achieving the target blood cyclosporine concentration, decreasing proteinuria and hypercholesterolemia, and increasing the blood total protein level in the child, which indicated the effectiveness of the ongoing treatment for the chief complaint.Conclusions: the data obtained suggest that laboratory monitoring of pharmacokinetic parameters in paediatric polypharmacy can increase the effectiveness of therapy and prevent adverse reactions and irrational combination of medicinal products.

Gastrointestinal tuberculosis following renal transplantation accompanied with septic shock and acute respiratory distress syndrome: a survival case presentation

BackgroundPost-transplant tuberculosis (PTTB) is a serious opportunistic infection in renal graft recipients with a 30-70 fold higher incidence compared to the general population. PTTB occurs most frequently within the first years after transplantation, manifesting as pulmonary or disseminated TB. Gastrointestinal TB (GITB) is a rare and potentially lethal manifestation of PTTB and may show delayed onset in renal transplant recipients due to the use of lower doses of immunosuppressants. Further, non-specificity of symptoms and the common occurrence of GI disorders in transplant recipients may delay diagnosis of GITB.Case presentationHere we report a rare survival case of isolated GITB in a renal transplant recipient, occurring seven years after transplantation. The patient’s condition was complicated by severe sepsis with positive blood culture Staphylococcus haemolyticus, septic shock, multiple organ failure including acute respiratory distress syndrome (ARDS) and acute renal failure, requiring mechanical ventilation, vasopressor circulatory support and intermittent hemodialysis. Furthermore, nosocomial infections such as invasive aspergillosis and Pseudomonas aeruginosa occurred during hospitalization. Antituberculosis therapy (rifampicin, isoniazid, ethambutol and pyrazinamide) was initiated upon Mycobacterium confirmation. Moreover, treatment with voriconazole due to the Aspergillus flavus and meropenem due to the Pseudomonas aeruginosa was initiated, the former necessitating discontinuation of rifampicin. After 34 days, the patient was weaned from mechanical ventilation and was discharged to the pulmonary ward, followed by complete recovery.ConclusionThis case offers a guideline for the clinical management towards survival of GITB in transplant patients, complicated by septic shock and multiple organ failure, including acute renal injury and ARDS.

Decreased Linezolid Serum Concentrations in Three Critically Ill Patients: Clinical Case Studies of a Potential Drug Interaction between Linezolid and Rifampicin

Linezolid is a valuable treatment option for treating infections caused by multi-resistant gram-positive pathogens. Lack of effective linezolid levels due to the co-administration of rifampicin has been described in healthy subjects. However, the clinical significance of this potential drug interaction (DI) for critically ill patients is still unclear. This was a retrospective analysis of 3 critically ill patients with the combination therapy of linezolid and rifampicin or rifampicin pre-treatment. Despite increasing the dose of linezolid, the majority of observed linezolid trough concentrations in all 3 patients were below 2 mg/l. Furthermore, linezolid trough concentrations remained below 2 mg/l after discontinuation of rifampicin. This potential DI between linezolid and rifampicin could lead to treatment failure. Therefore, we strongly recommend that linezolid serum concentrations be monitored in patients with rifampicin co-administration or rifampicin pretreatment.

Chronological Effects of Rifampicin Discontinuation on Cytochrome P450 Activity in Healthy Japanese Volunteers, Using the Cocktail Method

Cytochrome P450 (CYP) 1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A are major factors involved in the metabolism of clinically prescribed drugs. Because the time course after drug treatment discontinuation has received little attention, we aimed to clarify the chronological changes of rifampicin-induced CYP enzyme activities after rifampicin discontinuation. Thirteen volunteers took 450 mg of rifampicin once daily, and the cocktail method, which uses caffeine, losartan, omeprazole, dextromethorphan, and midazolam as CYP-specific probes, was repeatedly used for the evaluation of CYP levels. Concentrations of probes and metabolites were determined by liquid chromatography-tandem mass spectrometry. Seven-day rifampicin administration increased CYP2C19 and CYP3A enzyme activities. The induced CYP2C19 and CYP3A activities remained elevated at 4 days after rifampicin discontinuation and returned to baseline levels 8 days after rifampicin discontinuation. CYP1A2 and CYP2D6 enzyme activities showed no significant changes, and CYP2C9 enzyme activity was increased with rifampicin administration, with a tendency toward statistical significance. Drug interactions can occur even after rifampicin discontinuation.

Rifampicin-warfarin interaction leading to macroscopic hematuria: a case report and review of the literature

BackgroundRifampicin remains one of the first-line drugs used in tuberculosis therapy. This drug´s potential to induce the hepatic cytochrome P450 oxidative enzyme system increases the risk of drug-drug interactions. Thus, although the presence of comorbidities typically necessitates the use of multiple drugs, the co-administration of rifampicin and warfarin may lead to adverse drug events. We report a bleeding episode after termination of the co-administration of rifampicin and warfarin and detail the challenges related to international normalized ratio (INR) monitoring.Case presentationA 59-year-old Brazilian woman chronically treated with warfarin for atrial fibrillation (therapeutic INR range: 2.0-3.0) was referred to a multidisciplinary anticoagulation clinic at a university hospital. She showed anticoagulation resistance at the beginning of rifampicin therapy, as demonstrated by repeated subtherapeutic INR values. Three months of sequential increases in the warfarin dosage were necessary to reach a therapeutic INR, and frequent visits to the anticoagulation clinic were needed to educate the patient about her pharmacotherapy and to perform the warfarin dosage adjustments. The warfarin dosage also had to be doubled at the beginning of rifampicin therapy. However, four weeks after rifampicin discontinuation, an excessively high INR was observed (7.22), with three-day macroscopic hematuria and the need for an immediate reduction in the warfarin dosage. A therapeutic and stable INR was eventually attained at 50% of the warfarin dosage used by the patient during tuberculosis therapy.ConclusionsThe present case exemplifies the influence of rifampicin therapy on warfarin dosage requirements and the increased risk of bleeding after rifampicin discontinuation. Additionally, this case highlights the need for warfarin weekly monitoring after stopping rifampicin until the maintenance dose of warfarin has decreased to the amount administered before rifampicin use. In particular, patients with cardiovascular diseases and active tuberculosis represent a group with a substantial risk of drug-drug interactions. Learning how to predict and monitor drug-drug interactions may help reduce the incidence of clinically significant adverse drug events.

Acute rifampicin-associated interstitial tubulopathy in a patient with pulmonary tuberculosis: a case report

IntroductionRifampicin is one of the most effective antibiotics for treating tuberculosis, but it has been associated with adverse reactions, such as nephrotoxicity, sometimes resulting in acute renal failure with oligoanuria, and hepatotoxicity. Although deterioration of renal function, determined by acute tubulointerstitial nephritis and/or acute tubular necrosis, typically appears in patients receiving intermittent rifampicin therapy, some authors have also reported cases occurring during continuous rifampicin therapy.Case presentationWe describe the case of acute renal failure with polyuria occurring in a previously healthy 50-year-old Caucasian man undergoing continuous therapy with rifampicin for culture-confirmed pulmonary tuberculosis. The patient was admitted to the L. Spallanzani National Institute for Infectious Diseases, Rome, Italy, with a 1-month history of coughing, fever and weight loss. After 6 weeks of standard antituberculous treatment, progressive deterioration of his renal function was observed: creatinine levels rose from 38.9μmol/L to 318.2μmol/L and urine volume also progressively increased to reach a state of true polyuria (8 to 10L of urine per day). He was diagnosed with suspected acute rifampicin-induced renal failure. A renal biopsy showed focal segmental glomerulosclerosis associated with acute tubulointerstitial nephritis. Rifampicin was discontinued with excellent results: after 15 days his renal function began to improve and his serum creatinine values returned to normal.ConclusionA high index of suspicion for rifampicin-associated acute renal failure should be maintained in patients with pulmonary tuberculosis who develop progressive deterioration of renal function during treatment with rifampicin. Early diagnosis and discontinuation of rifampicin are of fundamental importance for recovering renal function.

Pharmacokinetics of Nevirapine in HIV and Tuberculosis–coinfected Children Receiving Antiretroviral Fixed-dose Combination Tablets While Receiving Rifampicin-containing Tuberculosis Treatment and After Rifampicin Discontinuation

We assessed the pharmacokinetics of nevirapine in HIV and tuberculosis-coinfected children while they were receiving nevirapine-containing fixed-dose combination tablets with rifampicin-based tuberculosis treatment and after discontinuation. The median age (range) was 9.7 (4.4-11.7) years. The nevirapine area under the concentration versus time curve from 0 to 12 hours and trough concentration with rifampicin were 85.3 (40.5-170.7) mg.h/mL and 6.4 (3.00-13.27) mg/mL, respectively, providing adequate exposure.

A CASE OF MILIARY TUBERCULOSIS WITH INTERSTITIAL NEPHRITIS DUE TO RE-ADMINISTRATION OF RIFAMPICIN TREATED SUCCESSFULLY WITH S T E ROID

A 26-year-old man was admitted to a hospital complaing of continuous high fever and abdominal swelling. As his sputum and ascites culture was positive for acid-fast bacilli and PCR-TB, he was diagnosed as miliary tuberculosis, tuberculous with pleuritis and peritonitis, and transferrd to our hospital. After initiation of treatment with isoniazid, rifampicin (RFP), ethambutol, and pyrazinamide, RFP was suspended because of direct-reacting hyperbilirubinemia. As the liver function recovered after discontinuation of RFP, low dose of RFP was re-administrated and renal dysfunction was observed. The renal dysfunction continued after discontinuation of suspicious drugs including RFP. As renal biopsy revealed interstitial nephritis, prednisolon 20 mg/day was started and renal function recovered quickly. From the clinical course and examination, we considered interstitial nephritis was due to re-administration of RFP and steroid therapy was effective.

Effects of CYP2B6 G516T polymorphisms on plasma efavirenz and nevirapine levels when co-administered with rifampicin in HIV/TB co-infected Thai adults

BackgroundCytochrome P450 2B6 (CYP2B6) metabolizes efavirenz and nevirapine, the major core antiretroviral drugs for HIV in Thailand. Rifampicin, a critical component of tuberculosis (TB) therapy is a potent inducer of CYP enzyme activity. Polymorphisms of CYP2B6 and CYP3A4 are associated with altered activity of hepatic enzyme in the liver and pharmacokinetics resulting in treatment efficacy. This study aimed to investigate whether CYP2B6 or CYP3A4 polymorphisms had effects on plasma efavirenz and nevirapine concentrations when co-administered with rifampicin in HIV/TB co-infected Thai adults.ResultsWe studied 124 rifampicin recipients with concurrent HIV-1/TB coinfection, receiving efavirenz (600 mg/day) (n = 65) or nevirapine (400 mg/day) (n = 59) based antiretroviral therapy (ART). The frequencies of GG, GT and TT genotypes of CYP2B6-G516T were 38.46%, 47.69% and 13.85% in efavirenz group and 44.07%, 52.54% and 3.39% in nevirapine group, respectively. The mean 12-hour post-dose plasma efavirenz concentration in patients with TT genotype at weeks 6 and 12 of ART and 1 month after rifampicin discontinuation (10.97 ± 2.32, 13.62 ± 4.21 and 8.48 ± 1.30 mg/L, respectively) were significantly higher than those with GT (3.43 ± 0.29, 3.35 ± 0.27 and 3.21 ± 0.22 mg/L, respectively) (p < 0.0001) or GG genotypes (2.88 ± 0.33, 2.45 ± 0.26 and 2.08 ± 0.16 mg/L, respectively) (p < 0.0001). Likewise, the mean 12-hour post-dose plasma nevirapine concentration in patients carrying TT genotype at weeks 6 and 12 of ART and 1 month after rifampicin discontinuation (14.09 ± 9.49, 7.94 ± 2.76 and 9.44 ± 0.17 mg/L, respectively) tended to be higher than those carrying GT (5.65 ± 0.54, 5.58 ± 0.48 and 7.03 ± 0.64 mg/L, respectively) or GG genotypes (5.42 ± 0.48, 5.34 ± 0.50 and 6.43 ± 0.64 mg/L, respectively) (p = 0.003, p = 0.409 and p = 0.448, respectively). Compared with the effects of CYP2B6-516TT genotype, we could observe only small effects of rifampicin on plasma efavirenz and nevirapine levels. After 12 weeks of both drug regimens, there was a trend towards higher percentage of patients with CYP2B6-TT genotype who achieved HIV-1 RNA levels <50 copies/mL compared to those with GT or GG genotypes. This is the first report to demonstrate the effects of CYP2B6 G516T polymorphisms on plasma efavirenz and nevirapine concentrations when co-administered with rifampicin in HIV/TB co-infected Thai adults.ConclusionsCYP2B6-TT genotype had impact on plasma efavirenz and nevirapine concentrations, while rifampicin co-administration had only small effects.

Mycophenolic acid area under the curve recovery time following rifampicin withdrawal

Renal transplant patients prescribed mycophenolate mofetil (MMF) may require treatment for tuberculosis with a regimen including the tuberculocidal drug rifampicin. MMF is an ester prodrug which is rapidly hydrolysed to the active compound, mycophenolic acid (MPA). Therapeutic drug monitoring of mycophenolate involves the measurement of MPA area under the curve (MPA-AUC0-12). Rifampicin is known to increase the metabolism and decrease enterohepatic recirculation of mycophenolic acid, (MPA). When MPA is monitored after the discontinuation of rifampicin, an important factor is the time required for the MPA area under the curve to return to the pre-rifampicin value. At present this is not known. This report describes one such renal allograft patient, on long term MMF and prescribed rifampicin by a local physician. As expected there was a clinically significant decrease in MPA-AUC0-12 Three weeks after rifampicin was discontinued the MPA-AUC0-12 was still only 65% of the pre-rifampicin value and only 55% of the steady state MPA-AUC0-12 measured six months later.

Clinical Aspects of Rifampicin-associated Pseudomembranous Colitis

Pseudomembranous colitis (PMC) is known to develop after antibiotic administration, but antituberculosis agents are rarely associated with this disorder. We report 6 cases of PMC after rifampicin administration; the clinical manifestations, laboratory findings, imaging findings, and clinical course are described. The median age of patients was 68 years (range, 54 to 82 y). All patients were diagnosed with active pulmonary tuberculosis by sputum smear and culture, and 2 suffered from type 2 diabetes mellitus. The average interval between initiation of antituberculosis therapy and the onset of diarrhea was 19.8 days. The anatomic distribution of PMC included the rectum and sigmoid colon in 5 cases and up to the hepatic flexure in 1 case. All patients were cured with medical treatment, which include discontinuation of rifampicin and oral metronidazole and vancomycin. PMC recurred in 1 patient after retreatment with rifampicin. Our findings suggest that patients who are treated with antituberculosis agents, who develop acute diarrhea during or after therapy, should be evaluated for PMC.

Crescentic glomerulonephritis associated with rifampicin in a patient co-infected with tuberculosis and human immunodeficiency virus

A 73-year-old man presented with acute renal failure after 3-month standard antituberculosis therapy with rifampicin for pulmonary tuberculosis. Previously undiagnosed human immunodeficiency virus (HIV) infection was found at the same time. A kidney biopsy showed crescentic glomerulonephritis and tubulointerstitial nephritis. Furthermore, endothelial tubuloreticular inclusions were seen on electron microscopy. Rifampicin was stopped because it was considered as the most possible cause responsible for the rapidly progressive glomerulonephritis (RPGN). Immunosuppressive therapy was not carried out because of the risk of aggravation of underlying infectious diseases including tuberculosis and HIV. Fortunately, renal function recovered 1 month after discontinuation of rifampicin. This case presented a clinical challenge in the differential diagnosis of the cause for RPGN in such a complex condition and the therapeutic dilemma regarding the use of immunosuppressive drugs.

Acute Tubulo-Interstitial Nephritis Requiring Dialysis Associated with Intermittent Rifampicin Use: Case Report

Rifampicin is one of the most effective antibiotics used for the treatment of tuberculosis and severe staphylococcal infections. Intermittent administration of high doses of rifampicin has been associated with frequent adverse reactions, including hepatotoxicity and nephrotoxicity, sometimes resulting in acute renal failure. We describe a case of rifampicin-associated acute renal failure, with biopsy findings of tubulointerstitial nephritis; inflammatory cells were characterized by immunohistochemistry, which showed immunoreactivity for CD3 and CD5 (T lymphocytes) and for CD68 (macrophages). The patient presented with a very rapid systemic reaction to the offending drug and rapid deterioration of renal function, which required dialysis treatment. The response to rifampicin discontinuation was excellent: no further therapy was required, as renal function began to improve within several days and returned to normal values (serum creatinine 1.17 mg/dl) seven months after the onset of symptoms. When prescribing rifampicin the physician should investigate previous use of the drug, because re-exposure is a critical factor in predicting the possibility of drug-induced acute renal failure.