Rifampicin Clarithromycin

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... 

CLARITHROMYCIN, TELITHROMYCIN RIFAMPICIN 1 levels of these macrolides Rifampicins induce metabolism of these macrolides Avoid co-administration for up to 2 weeks after stopping rifampicin... 

RIFAMYCINS MACROLIDES 1.1 levels of clarithromycin and telithromycin with rifampicin 2. t rifabutin levels with macrolides 1. Rifampicins induce metabolism of these macrolides 2. Inhibition of CYP3A4-mediated metabolism of rifabutin 1. Watch for poor response to clarithromycin and telithromycin, which may last up to 2 weeks after stopping rifampicin 2. Watch for early features of toxicity of rifabutin in particular, warn patients to report painful eyes... 

Resistant organisms. Initial resistance occurs in about 4% of isolates in the UK, usually to isoniazid. Multiple-drug-resistant tuberculosis, i.e. resistant to rifampicin and isoniazid at least, should be treated with three or four drugs to which the organisms are sensitive and should extend for 12-24 months after cultures become negative. Treatment of such cases requires expert management. Atypical mycobacteria are often resistant to standard drugs their virulence is low but they can produce serious infection in immunocompromised patients which may respond, e.g. to clarithromycin or a quinolone, often in combination. 

The interaction of clarithromycin with the rifamycins is complex. Clarithromycin inhibits CYP3A4, while both rifampicin and rifabutin induce P450 cytochromes,... 

After the addition of rifampicin, peak serum concentrations of clarithromycin fell markedly, from a mean of 5.8-2.5 pg/ml (67). At the same time the ratio of the serum concentrations of clarithromycin and its 14-OH metabohte was reversed from 3.3 1 to 1 2.7. There were similar, although less marked, changes after the addition of rifabutin 600 mg/day to a regimen that included clarithromycin 1000 mg/day. 

In patients with MAC infections taking rifabutin or rifampicin the addition of clarithromycin resulted in rifamycin-related adverse events in 77% of patients... 

Clinically important, potentially hazardous interactions with amantadine, anticholinergics, antidepressants, antimuscarinics, atazanavir, carbamazepine, clarithromycin, CYP2D6 inhibitors, CYP3A4 inducers, CYP3AF inhibitors, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, phenobarbital, phenytoin, rifampicin, ritonavir, saquinivir, St John s wort, telithromycin... 

Clinically important, potentially hazardous interactions with aminophylline, aspirin, carbamazepine, clarithromycin, cyclosporine, daclizumab, erythromycin, itraconazole, ketoconazole, live vaccines, oral contraceptives, phenobarbital, rifampicin, rifampin, troleandomycin, warfarin... 

CYP3A4 alprazolam, calcium channel blockers, cisapride, clarithromycin, cyclosporin A, erythromycin, HIV protease inhibitors, lidocaine, midazolam, simvastatin, terfenadine carbamazepine, dexamethsone, phenobarbital, phenytoin, rifampicin, St John s wort cimetidine, erythromycin, grapefruit juice, HIV protease inhibitors, itraconazole, ketoconazole... 

Rimonabant is partly metabolised by the cytochrome P450 isoenzyme C YP3A4. Ketoconazole, a potent CYKIA4 inhibitor, doubles the AUC of rimonabant. The manufacturers therefore expect that other potent CYP3A4 inhibitors (they name clarithromycin, itraconazole, nefazo-done, ritonavir, and teUthromycin) will also raise rimonabant levels, and they therefore advise caution on concurrent use. They similarly suggest that potent CYP3A4 inducers (such as carbamazepine, phenobarbital, phenytoin, rifampicin (rifampin) and St John s wort) may lower rimonabant levels. If concurrent use is necessary monitor to ensure that rimonabant remains effective. See Table 1.4 , (p.6), for a list of clinically relevant CYE 3A4 inducers and inhibitors. 

Rifabutin and azithromycin seem not to affect the serum levels of each other, but a very high incidence of neutropenia was seen in one study of the combination. Both rifabutin and rifampicin markedly reduce the serum levels of clarithromycin. Clarithromycin increases the serum levels of rifabutin and the combination is associated with an increased risk of uveitis and neutropenia. Rifampicin (rifampin) greatly reduces telithromycin levels and concurrent use is not recommended. 

Patients with lung disease due to MAC were treated with clarithromycin 500 mg twice daily. When rifampicin 600 mg daily was added, the mean serum levels of clarithromycin fell by almost 90% (from 5.4 to 0.7 micrograms/mL). Similar results are reported in another study. ... 

Numerous case reports also describe this interaction ciclosporin levels or AUC have been increased by two- to threefold, " with changes being seen within 3 to 6 days of clarithromycin 250 or 500 mg twice daily being started. " Another patient had a seven- to twelvefold rise in serum ciclosporin levels and acute renal failure within 3 weeks of starting to take clarithromycin 1 g daily. Another case report in a heart transplant patient taking ciclosporin found that the addition of rifampicin to clarithromycin negated the increase in ciclosporin levels seen with clarithromycin alone, and the ciclosporin dose requirement with concurrent clarithromycin plus rifampicin was similar to that before clarithromycin or rifampicin were started. ... 

Three patients needed increases in the dosage of ciclosporin when given rifampicin and erythromycin, although the latter normally reduces ciclosporin requirements.Another patient whose ciclosporin levels had been raised by clarithromycin , (p.l016), had a fall in their levels when rifampicin was added... 

Jenkins PA, Campbell lA, Banks J, Gelder CM, Prescott RJ, Smith AP. Clarithromycin vs ciprofloxacin as adjuncts to rifampicin and ethambutol in treating opportunist mycobacterial lung diseases and an assessment of Mycobacterium vaccae immunotherapy. Thorax 2008 63(7) 627-34. 

A 75-year-old woman developed progressively worse peripheral vision in both eyes after taking ethambutol 1200 mg/day for almost 1 year, plus clarithromycin and rifampicin for infection with Mycobacterium avium complex and Mycobacterium kansasii. Best corrected visual acuity was 20/80— in the right eye and 20/60-1-in the left eye. Eye movements were full. Slit lamp exam showed -1-1 nuclear sclerosis in both eyes. On fundoscopy the optic discs were not swollen or pale. A 30-2 Humphrey visual field showed bitemporal hemianopia. An MRI scan of the brain was normal, as was optical coherence tomography. 

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