Rifampicin interaction

Ambiguity also exists in the interpretation of the underlying mechanisms for the fexofenadine-rifampicin interaction. Pretreatment of rifampicin significantly decreased the systemic exposure of fexofenadine (a good P-gp substrate) in healthy volunteers (60). The Cmax and AUC of fexofenadine were decreased by two- and threefold, respectively, in volunteers after rifampicin treatment (600 mg/day for 6 days). On the basis of the assumption that fexofenadine... 

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 was first shown by Hartmann et al. 54 to have a specific inhibitory effect on RNA polymerase from E. coli. Later, other active ansamycins were found and RNA polymerases from a large variety of bacteria other than E. coli proved to be sensitive to the drug. More recently, an RNA polymerase from E. coli containing only one subunit and probably involved in the initiation of DNA replication (dna G gene product) has been shown to be resistant to rifampicin5 s This holds true also for the various mammalian RNA polymerases. In contrast to non-specific inhibitors of transcription such as actinomycin and mitomycin, rifampicin interacts specifically with the bacterial enzyme itself. With the aid of 14C-labelled rifampicin it could be shown that the drug forms a very stable complex with the enzyme in a molar ratio of 1 1S6> 57 The dissociation constant of this complex is 10-9 M at 37 °C and... 

A study in 10 healthy volunteers has suggested that rifampicin interacts with losartan (31). The AUCs of both losartan and its active metabolite were markedly reduced (about 30 and 40% respectively) when rifampicin 300 mg bd was given for 1 week. 

Robson, R. A. et al., Theophylline-rifampicin interaction non-selective induction of theophylline metabolic pathways, Br. J. Clin. Pharmacol, 18(3) 445-448, 1984. Boyce, E. G. et al.. The effect of rifampin on theophylline kinetics, J. Clin. Pharmacol, 26(8) 696-699, 1986. 

Tada Y, Tsuda Y, Otsuka T, Nagasawa K, Kimura H, Kusaba T, Sakata T. Case report nifed-ipine-rifampicin interaction attenuates the effect on blood pressure in a patient with essential hypertensicn AmJMcdSci (1992) 303,25-7... 

It seems possible that the general adverse hepatotoxic effects of halothane can slow the normal rate of phenytoin metabolism. One suggested explanation for the increased adverse effects on the liver is that, just as in animals, pre-treatment with phenobarbital and phenytoin increases the rate of drug metabolism and therefore the hepatotoxicity of halogenated hydrocarbons, including carbon tetrachloride and halothane. As well as increased metabolism, the halothane-rifampicin interaction might also involve additive hepatotoxicity. 

This seems to be the first and only report of this interaction, but what happened is consistent with the way rifampicin interacts with many other drugs. If rifampicin is added to hydroxychloroquine, the outcome should be well monitored. Be alert for the need to increase the hydroxychloroquine dosage. 

So far only four cases of an interaction between rifampicin and chloramphenicol appear to have been reported. However, the evidence is of good quality and in line with the way rifampicin interacts with other drugs, so this interaction should be taken seriously. There is a risk that serum chloramphenicol levels will become subtherapeutic. The authors of the second report point out that raising the chloramphenicol dosage may possibly expose the patient to a greater risk of bone marrow aplasia. They suggest delaying rifampicin prophylaxis in patients with invasive Haemophilus influenzae infections until the end of chloramphenicol treatment. 

Purohit SD, Johri SC, Gupta PR, Mehta YR, Bhatnagar M Ranitidine-rifampicin interaction... 

The documentation of these interactions is limited but what has been reported is consistent with the way rifampicin interacts with many other drugs. The clinical importance of some of these interactions between the benzodiazepines and related drugs and rifampicin has not yet been assessed but what is known suggests that the dosage of diazepam and nitrazepam may need to be increased if rifampicin is given. Be alert for a reduction in the effects of other similarly metabolised benzodiazepines (e.g. chlordiazepoxide, flurazepam). 

This appears to be an isolated case but it is consistent with the way rifampicin interacts with other drugs. Clozapine serum levels should be well monitored if rifampicin is added, being alert for the need to increase its dosage. An alternative (as in this case) is to use another antibacterial. However, note that there are reports of an interaction between clozapine and ciprofloxacin , (p.749). 

These reports are consistent with the way rifampicin interacts with many other drugs and therefore this interaction would seem to be of general clinical importance. It would be prudent to be alert for the need to raise the dosage of tacrolimus if rifampicin is added in any patient. 

Robson RA, Miners JO, Wing LMH, Birkett DJ. Theophylline-rifampicin interaction non-selective induction oftheophylline metabolic pathways. BrJC/znP/icnwaco/(1984) 18,445-8. 

As far as sinusoidal uptake is concerned, drug-drug interactions have also been reported between antituberculosis agents (rifamycin SV and rifampicin) and bromosulfophthalein in humans both drugs reduce the clearance of bromosul-fophthalein and also induce hyperbilirubinemia [108]. These results may be ac-... 

K., Interactions of rifamycin SV and rifampicin with organic anion uptake systems of human liver, Hepatology... 

NA /D, abd pain, bleeding, fevCT, T QT Interactions t Effects W7 atazanavir, clarithromycin, CT5rthromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfi-navir, ritonavir, saquinavir, telithromycin X effects W7 antacids, carbamazqjine, dexamethasone, phenobarbital, phenytoin, rifampicin, St. John s wort EMS Drug contains lactose, may cause D/abd discomfort in pts w/ lactose intolerance OD Sxs unknown symptomatic and supportive... 

There are some clinically important pharmacodynamic drug-drug interactions to be mentioned. Antipsychotics will potentiate the central depressant effects of sedatives and of alcohol. They will also increase the risk of respiratory-depressant effects of opiates. Inducers of drug metabolic enzymes like for example rifampicin and several antiepileptics, may increase the elimination rate of antipsychotic agents and thus decrease their efficacy. 

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... 

Beta-blockers interact with a large number of other medications. The combination of beta-blockers with calcium antagonists should be avoided, given the risk for hypotension and cardiac arrhythmias. Cimetidine, hydralazine, and alcohol all increase blood levels of beta-blockers, whereas rifampicin decreases their concentrations. Beta-blockers may increase blood levels of phenothiazines and other neuroleptics, clonidine, phen-ytoin, anesthetics, lidocaine, epinephrine, monoamine oxidase inhibitors and other antidepressants, benzodiazepines, and thyroxine. Beta-blockers decrease the effects of insulin and oral hypoglycemic agents. Smoking, oral contraceptives, carbamazepine, and nonsteroidal anti-inflammatory analgesics decrease the effects of beta-blockers (Coffey, 1990). 

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