Rifampicin adverse effects

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. 

The adverse effects of amprenavir in patients treated with combination therapy included nausea, vomiting, diarrhea, epigastric pain, flatulence, paresthesia, headache, rash, and fatigue (4). The contribution of a single drug to the observed adverse effects is difficult to establish. Amprenavir inhibits CYP3A4 to a greater extent than saquinavir, and to a much lesser extent than ritonavir (5). Co-administration with rifampicin and rifabutin should be avoided. Those who take... 

Hepatotoxicity is the most important adverse effect of antituberculosis drug therapy. Isoniazid, rifampicin, and pyrazinamide are the main culprits. There is wide variability in the risk of hepatotoxic reactions reported from different parts of the world or in different populations (for example African-American women in the postpartum period) (SEDA-24, 353). 

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. 

A 300 mg dose of rifabutin is usually well tolerated. Adverse effects include neutropenia, thrombocytopenia, rash, and gastrointestinal disturbances (nausea, flatulence). Myositis (12) and uveitis (13) are rarely observed. The drug-induced lupus-like syndrome has been linked in a few cases with rifampicin and rifabutin. 

Chronic alcohohsm is an important risk factor for adverse effects of the rifamycins. In 79 consecutive patients taking rifampicin in combination with isoniazid and another drng, there was a high incidence of acnte chnical liver... 

Thrombocytopenia is a rare adverse effect of vancomycin and may be associated with the presence of vancomycin-dependent antiplatelet IgG antibodies. Reports of drug-induced thrombocytopenia have been systematically reviewed (51). Among the 98 different drugs described in 561 articles the following antibiotics were found with level I (definite) evidence co-trimoxazole, rifampicin, vancomycin, sulfisoxazole, cefalothin, piperacillin, methicillin, novobiocin. Drugs with level II (probable) evidence were oxytetracycline and ampicillin. 

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. 

In one study 15 patients with tuberculosis, who had taken rifampicin 450 mg daily for at least 15 days, were given co-trimoxazole (trimethoprim 320 mg and sulfamethoxazole 800 mg 12-hourly) for 5 to 10 days. Rifampicin levels were measured at 5 time points over 6 hours before and during co-trimoxazole treatment. At 4 and 6 hours, rifampicin levels were significantly higher (27% and 56%, respectively) during co-trimoxazole treatment, but peak levels were only increased by about 18%. Concurrent use did not result in any increase in adverse effects over the study period. ... 

Rifabutin and rifampicin (rifampin) cause a very marked fall in delavirdine plasma levels rifabutin levels are raised when the delavirdine dose is increased to compensate for this. Rifabutin does not affect efavirenz levels, whereas efavirenz decreases rifabutin levels. There is usually no important interaction between rifabutin and nevirapine, although some patients may have a higher risk of rifabutin adverse effects. 

Rifampicin (Rifampin). The manufacturer states that the AUC of nevirapine was reduced by 58% by rifampicin in 14 subjecls, when compared with historical data. There was no change in steady-state rifampicin pharmacokinetics. Based on these pharmacokinetic data, the manufacturer suggests that the concurrent use of rifampicin with nevirapine is not recommended, and that rifabutin may be considered instead, with close monitoring of adverse effects. ... 

Rifampicin (rifampin) bioavaiiabiiity is increased by indinavir, but amprenavir has no effect. Rifampicin markedly reduces the bioavailability of amprenavir, atazanavir/ritonavir, indinavir, indinavir with ritonavir, iopinavir/ritonavir, nelfinavir and saquinavir, but oniy modestiy reduces that of ritonavir. The effects of rifampicin on iopinavir/ritonavir and saquinavir/ritona-vir can be overcome by increasing the protease inhibitor dose, but this appears to increase adverse effects (hepatotoxicity). 

Powell-Jacksonl Gray BJ, Heaton RW,(2ostelloJF, Williams R,Ei lishJ Adverse effect of rifampicin administration on steroid-dependent asthma. Am Rev Respir Dis (1983) 128,... 

Rifampicin reduces the levels of mycophenolic acid (the active metabolite of mycophenolate) and increases the leveis of the metabolite associated with mycophenolate adverse effects. 

A subsequent study by the same authors in 8 kidney transplant patients taking mycophenolate 750 mg to 1 g twice daily found that rifampicin 600 mg daily for 8 days decreased the AUC0.12 and peak levels of mycophenolic acid by 17.5% and 18.5%, respectively. Glucuronide levels were increased and the AUC0.12 and peak levels of the acyl glucuronide metabolite, which has been associated with an increase in mycophenolate adverse effects, was significantly increased by 193% and 121%, respectively. ... 

There seem to be no reports of adverse effects in other patients given both drugs and the evidence for this interaction is by no means conclusive. Although rifampicin can affect thyroid hormones, it appears that healthy individuals can compensate for this. Since hypothyroid patients may not be able to compensate in the same way, bear this interaction in mind if rifampicin is given to a patient taking levothyroxine. 

Comparative studies In a prospective comparison of a combination of rifampicin and linezolid with a combination of rifampicin and co-trimoxazole in the treatment of bone and joint infections in 56 adults, 36 had infected orthopedic devices and 20 had chronic osteomyelitis [80. Patients who discontinued antibiotic therapy within 4 weeks of starting treatment were considered to be cases of treatment failure and were excluded. The rates of adverse effects were similar in the two groups 43% versus 46% respectively, and led to... 

The adverse effect profile of roflmnilast has been described previously. However, new data became available recently. A systematic review smnmarised the available data on adverse effects and drug reactions of roflmnilast. This systematic review was based on six clinical trials with a total population of 9102 COPD patients, with the study duration ranging between 24 and 52 weeks [89 ]. Roflmnilast is metabolised by CYP 3A4, CYP 2C19 and CYP 1A2. Inhibitors of these enzymes such as erythromycin or ketoconazole were shown to increase the activity and half-life of roflumilast. In contrast, drugs that induced these enzymes, like rifampicin, had the opposite effect, reducing the activity and half-life of roflumilast. Roflumilast did not significantly interact with montelukast, budesonide, or antacids. 

A number of reports have appeared on the adverse effects of rifampicin on the kidney. Courtois and de Coninck reported a case of acute renal failure requiring several transfusions and multiple periods of haemodialysis. Nephrotoxicity in this case developed when rifampicin was re-introduced into the treatment schedule after a gap of several weeks (25 ). A similar case was reported by Hanzl et at. from Germany (26 ) and a further case in which the nephrotoxicity became manifest during a course of twice weekly therapy was described by Nessi et al. (27 ). These authors also reviewed the cases reported to date in the literature, showing that interruptions of treatment or treatment on an intermittent basis are a common feature to most of the reported cases. Eventual renal failure may or may not be preceded by a flu-like illness. Renal biopsy has been carried out in approximately a third of the reported cases and a picture of tubular interstitial necrosis has been seen. The results of immunological tests have not been consistent, and antibodies to rifampicin have not been demonstrated in every case. It is perhaps worthy of note that renal failure has only, so far, been reported in patients who have had a fairly long course of treatment. 

A brief, but interesting communication from the United States described the incidence of adverse effects in 61 healthy subjects who elected to take rifampicin prophyl-actically after being in close contact with a patient who died of meningococcal meningitis. Only 18 of the 61 people reported no adverse reactions. The dosage used was 600 mg every 12 hours for 4 doses. Six of the subjects were unable to take all 4 doses because of side effects. The commonest reactions were nausea, headache, dizziness and vomiting (24 ). 

Rifampicin toxicity is becoming of greater importance in the treatment of leprosy. Several studies have recently been reported in which rifampicin was used in combination with Isoprodian, a combination of dapsone, isoniazid and prothionamide. The commonest adverse effects observed on this combination are gastrointestinal disturbances and mild hepatitis, manifested either as abnormalities in biochemical parameters or clinically by jaundice. One case of exfoliative dermatitis was reported from a trial carried out in South India (35 ). 

An interesting and unusual adverse effect attributed to pyrazinamide was described in a paper from the United States (54 ). A patient was described who suffered several attacks of acute intermittent porphyria whilst under treatment for tuberculosis. The first attack occurred after 18 months therapy with isoniazid and ethambutol. The second episode occurred after 14 days treatment with rifampicin, 7 days treatment with pyrazinamide and 3 days treatment with streptomycin. The patient was subsequently treated successfully with a combination of rifampicin, ethambutol and capreomycin. The compounds were investigated for their capacity to induce hepatic delta-aminolaev-ulinic acid synthesis in an in vitro preparation of rat Uver. The results showed that pyrazinamide had a greater potential for inducing the enzyme activity than any of the other compounds. It is worthy of note, however, that in this in vitro system para-aminosalicylic acid, rifampicin, cycloserine and ethionamide all induced increased delta-aminolaevulinic acid synthesis. 

There has been some overlap in recent publications relating to adverse effects of drugs used in leprosy and tuberculosis because of the increasing use in leprosy of rifampicin and isoprodian which contains isoniazid, prothionamide and dapsone. Publications relating to adverse effects produced by a combination of rifampicin and isoprodian have already been referred to in the section dealing with drugs used in tuberculosis. 

ALMOTRIPTAN, ELETRIPTAN CARBAMAZEPINE Possible 1 plasma concentrations of almotriptan and risk of inadequate therapeutic efficacy. Risk of serotonin syndrome One of the major metabolizing enzymes of almotriptan - CYP3A4 isoenzymes - is induced by rifampicin. As there are alternative metabolic pathways, the effect may not be significant and can vary from individual to individual. Triptans and carbamazepine are both stimulants of 5-HT receptors, and carbamazepine in addition prevents the reuptake of 5-HT Be aware of possibility of l response to triptan, and consider T dose if considered to be due to interaction. Be aware of the possibility of the occurrence of serotonin syndrome >- For signs and symptoms of serotonin toxicity, see Clinical Features of Some Adverse Drug Interactions, Serotonin toxicity and serotonin syndrome... 

Careful monitoring and the addition of pyridoxine to isoniazid have reduced the number of adverse drug effects in tuberculosis. Awareness of potentially severe hepato-toxic reactions is vital, because hepatic failure may be a devastating and often fatal condition. Fulminant hepatic failure caused by rifampicin, isoniazid, or both has been described (2). 

The interaction between doxycycline and rifampicin is established and of clinical importance. Monitor the effects of concurrent use and increase the doxycycline dosage as necessary. No clinically important adverse interaction appears to occur between doxycycline and streptomycin. 

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