rifampin and Hepatitis-C--Chronic

The fixed-dose combination of the direct acting antivirals glecaprevir (GLE) and pibrentasvir (PIB) is an oral, once-daily treatment for all six major genotypes of chronic hepatitis C virus infection. A single and multiple-dose rifampin study (N = 12) and a carbamazepine study (N = 12) were conducted in healthy subjects to evaluate the effects of CYP3A/P-gp induction and OATP inhibition on the pharmacokinetics of GLE and PIB. In study 1, GLE 300 mg + PIB 120 mg was administered as a single dose either alone, after single and multiple daily doses of rifampin 600 mg, or 24 h after the last rifampin dose. In study 2, GLE 300 mg + PIB 120 mg was administered as a single dose either alone or after multiple doses of carbamazepine 200 mg. Relative to GLE + PIB alone, exposure of GLE was significantly increased by the first co-administered rifampin dose due to OATP inhibition, significantly decreased 24 h after the last rifampin dose due to CYP3A/P-gp induction, and slightly increased when co-administered with steady-state rifampin due to a combination of inhibition and induction forces. Exposure of PIB was not affected when co-administered with the first rifampin dose but was significantly decreased with steady-state rifampin co-administration, or 24 h after the last rifampin dose due to P-gp induction. Carbamazepine significantly decreased GLE and PIB exposure, mainly attributed to P-gp induction. The regimens tested were generally well-tolerated by the subjects and no new safety issues were identified.

Topics: Antiviral Agents; Cytochrome P-450 CYP3A; Drug Interactions; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Organic Anion Transporters; Rifampin

The safety of rifabutin replacing rifampicin among adults having rifampicin-related adverse reactions (ARs) during the treatment of tuberculosis remains unknown.. From June 2006 to June 2010, a total of 2868 newly treated tuberculosis patients without HIV infection in a referral hospital were screened in this retrospective cohort study.. Among the screened patients, a total of 221 (8%) patients who received rifabutin replacing rifampicin were included. Of these patients, 158 (72%) tolerated rifabutin during treatment, but 47 (21%) and 16 (7%) experienced mild and severe rifabutin-related ARs (including neutropenia, severe hepatitis and uveitis), respectively, and needed to discontinue rifabutin. Those having previous rifampicin-related arthralgia, dermatological events and cholestasis had a higher AR recurrence rate (60%, 23% and 9%, respectively) than others (5% for hepatitis and gastrointestinal intolerance and 0% for flu-like syndrome, neutropenia and others; P < 0.01). Multivariate logistic regression analysis showed that females (OR 3.35; 95% CI 1.06-10.56; P = 0.04) and patients with hepatitis virus B (HBV) or hepatitis C virus (HCV) coinfection (OR 3.72; 95% CI 1.19-11.67; P = 0.02) were at a higher risk of rifabutin-related severe ARs. No development of new drug resistance and no relapse of tuberculosis were found during 2 years of follow-up.. Rifabutin replacing rifampicin was well tolerated in most adults who had rifampicin-related ARs. Females and those with HCV or HBV coinfection were more prone to rifabutin-related severe ARs and required more cautious monitoring.

Topics: Adult; Aged; Aged, 80 and over; Antitubercular Agents; Cohort Studies; Drug-Related Side Effects and Adverse Reactions; Female; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Male; Middle Aged; Retrospective Studies; Rifabutin; Rifampin; Tuberculosis

We herein report a clinical pitfall regarding the treatment of a case of pulmonary tuberculoma in a patient with chronic hepatitis C. The patient presented with both chronic hepatitis C and pulmonary tuberculoma, and we initiated treatment of the chronic hepatitis C first due to the potential for liver injury; however, the patient's condition worsened in terms of the pulmonary tuberculosis. This case highlights the need to select the initial treatment for pulmonary tuberculoma, not chronic hepatitis C. In addition, we report that, although the administration of anti-tuberculosis chemotherapy regimens containing pyrazinamide (PZA) substantially increases the incidence of drug-induced hepatitis in patients with chronic hepatitis, we were fortunately able to use PZA without observing drug-induced hepatitis in this case because we closely monitored the patient's liver function.

Topics: Antitubercular Agents; Antiviral Agents; DNA, Viral; Drug Therapy, Combination; Female; Follow-Up Studies; Hepacivirus; Hepatitis C, Chronic; Humans; Image-Guided Biopsy; Isoniazid; Lung; Middle Aged; Mycobacterium tuberculosis; Practice Guidelines as Topic; Pyrazinamide; Rifampin; Tomography, X-Ray Computed; Tuberculoma; Tuberculosis, Pulmonary

Acquired ichthyosis is an uncommon disease usually associated with different systemic diseases. Its characteristic clinical sign is symmetrical scaling of the skin. We report a case of acquired ichthyosis revealing hepatic and lymph node tuberculosis.. A 41-year-old man was admitted to our hospital with weight loss and generalized acquired ichthyosis. Ultrasonography and computer tomography showed enlargement of abdominal lymph nodes. Lymph node and liver biopsy samples were taken during exploratory laparotomy and revealed multiple lymphoepitheliomas with Langhans-type giant cells and central caseous necrosis. The skin lesions resolved progressively after 5 months of antituberculous therapy.. Ichthyosis occurring in adulthood is often a sign of internal disease, especially malignant conditions. It has also been associated with autoimmune and infectious diseases, sarcoidosis and drugs. It is only rarely reported among patients with tuberculosis but it is possible that the ichthyosis in this case was due to weight loss and deterioration of the patient's general condition.

Topics: Adult; Antibiotics, Antitubercular; Antitubercular Agents; Biopsy; Drug Therapy, Combination; Follow-Up Studies; Hepatitis C, Chronic; Humans; Ichthyosis; Isoniazid; Laparotomy; Liver; Lymph Nodes; Male; Pyrazinamide; Rifampin; Time Factors; Treatment Outcome; Tuberculosis, Hepatic; Tuberculosis, Lymph Node

We report the case of a 36-year-old patient who experienced an isolated acute pulmonary homograft endocarditis two years after a Ross procedure for aortic valve infective endocarditis.

Topics: Adult; Ampicillin; Aortic Valve; Bioprosthesis; Combined Modality Therapy; Drug Therapy, Combination; Endocarditis, Bacterial; Enterococcus faecalis; Gentamicins; Gram-Positive Bacterial Infections; Heart Valve Prosthesis; Hepatitis C, Chronic; HIV Infections; Humans; Male; Methadone; Prosthesis-Related Infections; Pulmonary Valve; Rifampin; Substance Abuse, Intravenous; Transplantation, Autologous