Hepatitis rifampicin

Liver damage is the most common adverse effect of pyrazinamide (6). It varies from asymptomatic alteration of hver function detectable only by laboratory tests, through a mild syndrome characterized by fever, anorexia, malaise, hver tenderness, hepatomegaly, and splenomegaly, to more serious reactions with clinical jaundice, and finally the rare form with progressive acute yellow atrophy and death. As most patients take a combined regimen of pjrazinamide with isoniazid and rifampicin, it is difficult to determine which of the three drugs causes the hepatotoxicity it could be due to a combined effect (7). As with isoniazid and rifampicin, hepatic function should initially be monitored every few weeks. 

Pessayre D. Present views on isoniazid and isoniazid-rifampicin hepatitis. Agressologie 1982 23(A) 13-5. 

Scheuer PJ, Lai L, Summerfield JA, Sherlock S (1974) Rifampicin hepatitis. A clinical and histological study. Lancet 1 421... 

Antimicrobial resistance to rifamycins develops rapidly both in vitro and in vivo [65,85,86], As a consequence, all the three members of the family (i.e. rifampicin, rifabutin and rifapentine) are used clinically as components of combination therapies [65,87], Being structurally related, rifaximin could share this potential. And indeed resistance rates, recorded in fecal strains of Enterobacteriaceae, Enterococcus, Bacteroides, Clostridium and anaerobic cocci, ranged between 30 and 90% after short-term (5 days) antibiotic (800 mg daily) treatment [82], A similar pattern was observed in 10 patients with hepatic encephalopathy after treatment with rifaximin 1,200 mg/day for 5 days [80]. 

By using in vitro preparations of human enzymes it is possible to predict those antibiotics that will adversely affect the metabolism of other drugs [110]. Such studies have shown that rifaximin, at concentrations ranging from 2 to 200 ng/ml, did not inhibit human hepatic cytochrome P450 isoenzymes 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1 and 3A4 [34], In an in vitro hepatocyte induction model, rifaximin was shown to induce cytochrome P450 3A4 (CYP3A4) [34], an isoenzyme which rifampicin is known to induce [109],... 

Interesting information stems from studies of the hepatotoxic effect of the concomitant administration of rifampicin, another antituberculostatic drug (and a potent inducer of cytochrome P450) often used in combination with isoniazid. Rifampicin alone is not hepatotoxic but increases significantly the incidence of hepatitis in patients simultaneously dosed with isoniazid. In human volunteers (6 slow and 8 rapid acetylators), daily administration of rifampicin increased the release of hydrazine from isoniazid [180], In slow acetylators, the proportion of the dose metabolized to hydrazine increased... 

Rifabutin is a rifamycin used for prophylaxis against Mycobacterium avium complex infections in patients with low CD4 count. As with rifampicin it induces hepatic enzymes, although to a lesser extent than rifampicin, and the effectiveness of some drugs including oral contraceptives may be reduced. 

Patients should be warned that rifampicin colors urine, tears and other body fluids reddish-orange. Adverse effects further include rashes and pruritus and gastrointestinal complaints like nausea, anorexia and diarrhoea. With intermittent therapy a probably allergic hypersensitivity reaction can occur which mostly manifests itself as a flu-like syndrome with fever but can also result in nephritis and acute tubular necrosis. Elevation of serum transaminase levels occur frequently but clinical hepatitis is rare. Fatal outcome has been reported however. 

Rifampicin (child 10 mg/kg up to) 600 mg (<50kg 450 mg) orally, for 6 months 15 mg/kg up to 900 mg orally, for 6 months 15 mg/kg up to 600 mg orally, for 6 months GI upset Hepatitis Bleeding problem Flu-like symptoms Rash Significant interactions with many drugs. Colors body fluids orange. May discolor soft contact lenses... 

Cyclosporin is metabolised by the hepatic cytochrome P-450 enzyme system, and enzyme induction by phenobarbital, phenytoin, carbamazepine, or rifampicin will drastically increase the clearance of cyclosporin. Concurrent administration of these drugs has caused rejection of transplanted organs. Conversely, the use of enzyme inhibitors, such as erythromycin or the azole antifungal agents, e.g. ketoconazole, will increase the blood concentrations of cyclosporin leading to an increased risk of toxic side effects. 

The systemic availability of fluvastatin is reduced by the hepatic enzyme inducer rifampicin (1). 

Hypothyroidism developed within 2 weeks of rifampicin therapy in these patients and resolved when it was withdrawn. Rifampicin increases thyroxine clearance, possibly by enhancing hepatic thyroxine metabolism and the biliary excretion of iodothyronine conjugates. In healthy volunteers rifampicin reduces circulating thyroid hormone concentrations without affecting thyrotropin, suggesting that rifampicin directly reduces thyroid hormone concentrations. 

The antibiotics rifamycin SV and rifampicin reduce Sulfobromophthalein (BSP) elimination in humans. Using injected oocytes, Vavricka et al. (2002) demonstrated that rifampcin is transported by OATP-C and OATP8 and that both rifampicin and rifamycin SV inhibit OATP-C, 8, -B and -A mediated BSP uptake. These results show that rifamycin SV and rifampicin interact with OATP-mediated substrate transport to different extents. Inhibition of human liver OATPs can explain the previously observed effects of rifamycin S V and rifampicin on hepatic organic anion elimination. 

Rifampicin is an enzyme inducer and can increase the incidence and severity of isoniazid-induced hepatitis. Carbamazepine is an enzyme induction agent and interacts with isoniazid, increasing its hepatotoxicity. Isoniazid toxicity is associated with fast acetylator genotype. Although his phenotype was unknown, the interaction with carbamazepine increases risk of this toxicity. 

Acceleration of hepatic coumarin metabolism enzyme induction, e.g., by carbamazepine, rifampicin ... 

DISOPYRAMIDE ANTIBIOTICS-RIFAMPICIN Disopyramide levels are 1 by rifampicin Rifampicin induces hepatic metabolism of disopyramide Watch for poor response to disopyramide check serum levels if necessaiy... 

BETA-BLOCKERS RIFAMPICIN L plasma concentrations and efficacy of bisoprolol, carvedilol, celiprolol, metoprolol and propanolol Rifampicin induces hepatic enzymes (e.g. CYP2C19), which t metabolism of the beta-blockers in addition, it may also t P-gp expression Monitor PR and BP watch for poor response to beta-blockers... 

DIGITOXIN ANTIBIOTICS - RIFAMPICIN Plasma concentrations of digitoxin may be halved by rifampicin Due to T hepatic metabolism Watch for poor response to digitoxin... 

PACLITAXEL 1. ANTIBIOTICS-rifampicin 2. ANTIDEPRESSANTS-St John s wort 3. ANTIEPILEPTICS -carbamazepine, phenobarbital, phenytoin 1 plasma concentration of paclitaxel and 1 efficacy of paclitaxel Due to induction of hepatic metabolism of paclitaxel by the CYP isoenzymes Monitor for clinical efficacy and need to T dose if inadequate response is due to interaction... 

CORTICOSTEROIDS RIFAMPICIN 1 plasma concentrations of corticosteroids and risk of poor or inadequate therapeutic response, which would be undesirable if used for e.g. cerebral oedema Due to induction of hepatic metabolism by the CYP3A4 isoenzymes Closely monitor therapeutic response - clinically, by ophthalmoscopy and radiologically - and T dose of corticosteroids for desired therapeutic effect... 

OPIOIDS RIFAMPICIN 1 effect of alfentanil, codeine, methadone and morphine Rifampicin t hepatic metabolism of these opioids (alfentanil by CYP3A4, codeine by CYP2D6, morphine unknown). Rifampicin is also known to induce intestinal P-gp, which may 1 bioavailability of oral morphine Be aware that alfentanil, codeine, methadone and morphine doses may need to be t... 

RIFAMPICIN QUINUPRISTIN/ DALFOPRISTIN Risk of hepatic toxicity Additive effect Monitor LFTs closely... 

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