Delavirdine Clarithromycin

Clinically important, potentially hazardous interactions with amprenavir, atazanavir, clarithromycin, delavirdine, grapefruit juice, indinavir, itraconazole, ketoconazole, nefazodone, ritonavir, saquinavir, telithromycin, voriconazole... 

Clinically important, potentially hazardous interactions with almotriptan, amprenavir, clarithromycin, delavirdine, efavirenz, erythromycin, indinavir, naratriptan, nelfinavir, ritonavir, rizatriptan, saquinavir, sibutramine, sumatriptan, troleandomycin, zolmitriptan... 

The NNRTIs are substrates of the cytochrome P450 isoenzyme CYP3A4, which is inhibited by clarithromycin. Delavirdine is also reported to inhibit CYP3A4, whereas efavirenz and nevirapine induce CYP3A4. Therefore alterations in the metabolism of these drugs by CYP3A4 results in the altered levels seen. 

Drugs that may affect indinavir include didanosine, aldesleukin, anticonvulsants, atazanavir, nelfinavir, nevirapine, omeprazole, rifapentine, ritonavir, clarithromycin, azole antifungals, rifamycins, delavirdine, efavirenz, St. John s wort. 

Drugs that may affect delavirdine include the following Anticonvulsants, antacids, clarithromycin, didanosine, fluoxetine, histamine H2 antagonists, ketoconazole,... 

Drugs that may be affected by delavirdine include the following Clarithromycin, indinavir, amprenavir, benzodiazepines, cisapride, dihydropyridine calcium channel blockers, ergot derivatives, quinidine, sildenafil, warfarin, saquinavir, and didanosine. 

Others Acetaminophen, amiodarone, carbamazepine, delavirdine, efavirenz, nevirapine, quinidine, repaglinide, sildenafil, tadalafil, trazodone, vardenafil Amiodarone, amprenavir, atazanavir, ciprofloxacin, cisapride, clarithromycin, diltiozem, erythromycin, fluconazole, fluvoxamine, grapefruit juice (in high ingestion), indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, norfloxacin, ritonavir, telithromycin, troleandomycin, verapamil, voriconazole Carbamazepine, efavirenz, glucocorticoids, macrolide antibiotics, nevirapine, phenytoin, phenobarbital, rifabutin, rifapentine, rifampin, St. John s wort... 

Drugs that may inhibit cytochrome P450 metabolism of other drugs include amiodarone, androgens, atazanavir, chloramphenicol, cimetidine, ciprofloxacin, clarithromycin, cyclosporine, delavirdine, diltiazem, diphenhydramine, disulfiram, enoxacin, erythromycin, fluconazole, fluoxetine, fluvoxamine, furanocoumarins (substances in grapefruit juice), indinavir, isoniazid, itraconazole, ketoconazole, metronidazole, mexile-tine, miconazole, nefazodone, omeprazole, paroxetine, propoxyphene, quinidine, ritonavir, sulfamethizole, verapamil, voriconazole, zafirlukast, and zileuton. 

Delavirdine is extensively metabolized to inactive metabolites by the CYP3A and CYP2D6 enzymes. However, it also inhibits CYP3 A and thus inhibits its own metabolism. In addition to its interactions with other antiretroviral agents (see Table 49 1), delavirdine will result in increased levels of numerous agents (Table 49-3). Dose reduction of indinavir and saquinavir should be considered if they are administered concurrently with delavirdine. Delavirdine plasma concentrations are reduced in the presence of antacids, phenytoin, phenobarbital, carbamazepine, rifabutin, and rifampin concentrations are increased during coadministration with clarithromycin, fluoxetine, dexamethasone, and ketoconazole. 

Clinically important, potentially hazardous interactions with acetylcysteine, adenosine, aprepitant, aripiprazole, buprenorphine, caffeine, charcoal, clarithromycin, clobazam, dorazepate, clozapine, darunavir, dasatinib, delavirdine, dexamethasone, diltiazem, doxacurium, erythromycin, felodipine, fesoterodine, fosamprenavir, imatinib, influenza vaccines, lacosamide, lapatinib, levetiracetam, lopinavir, methylprednisolone, midazolam, nelfinavir, nilotinib, piracetam, prednisolone, propoxyphene, ritonavir, rivaroxaban, rufinamide, solifenacin, St John s wort, telithromycin, temsirolimus, terbinafine, tolvaptan, troleandomycin, verapamil, voriconazole... 

Clinically important, potentially hazardous interactions with atazanavir, azithromycin, bosentan, cholestyramine, clarithromycin, cyclosporine, darunavir, delavirdine, erythromycin, exenatide, fenofibrate, fosamprenavir, gemfibrozil, grapefruit juice, imatinib, itraconazole, red rice yeast, tacrolimus, telithromycin, tipranavir, tolvaptan, verapamil... 

Clinically important, potentially hazardous interactions with amprenavir, aprepitant, atazanavir, carbamazepine, chlorpheniramine, cimetidine, clarithromycin, clorazepate, CNS depressants, darunavir, delavirdine, dexamethasone, efavirenz, erythromycin, esomeprazole, fluconazole, fluoxetine, fosamprenavir, grapefruit juice, griseofulvin, imatinib, indinavir, itraconazole, ivermectin, ketoconazole, lopinavir, nelfinavir, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, ritonavir, roxithromycin, saquinavir, St John s wort, telithromycin, tipranavir... 

Acetaminophen, aldrin, alfentanil, amiodarone, aminopyrine, amitriptyline, amprenavir, androstenedione,antipyrine, astemizole, benzphetamine, budesonide, carbamazepine, celecoxib, chlorpromazine, chlorzoxazone, cisapride, clarithromycin, clozapine, cocaine, codeine, cortisol, cyclophosphamide,cyclosporin, dapsone, delavirdine, dextromethorphan, digitoxin, diltiazem, diazepam, erythromycin, 17j3-estradiol, ethinylestradiol, etoposide, felbamate, fentanyl, flutamide, hydroxyarginine, ifosphamide, imipramine, indinavir, ketoconazole, lansoprazole, loratidine, losartan, lovastatin, (iS)"mephen3d in, methadone, mianserin, miconazole, mifepristone, nelfinavir, nevirapine, nicardipine, nifedipine, odansetron, omeprazole, orphenadrine, proguanil, propafenone, quinidine, quinine, rapamycin, retinoic acid, ritonavir, saquinavir, selegiline, serindole, sufentanil, sulfinpyrazone, tacrolimus, tamoxifen, tamsulosin, taxol, teniposide, terfenadine, tetrahydrocannabinol, theophylline, toremifene, triazolam, trimethadone, trimethoprim, troleandomycin, verapamil, warfarin, zatosetron, Zolpidem, zonisamide... 

A4 Amiodarone, azole antifungals, cimetidine, clarithromycin, cyclosporine, erythromycin, fluoroquinolones, grapefruit juice, HIV protease inhibitors, metronidazole, quinine. SSRIs, tacrolimus Antiarrhythmics, antidepressants, azole antifungals, benzodiazepines, calcium channel blockers, cyclosporine, delavirdine, doxorubicin, efavirenz, erythromycin, estrogens, HIV protease inhibitors, nefazodone. paclitaxel, proton pump inhibitors, HMG-CoA reductase inhibitors, rifabutin, rifampin, sildenafil, SSRIs, tamoxifen, trazodone, vinca anticancer agents... 

Delaviradine is rapidly absorbed by oral administration and peak plasma concentration was obtained in 1 hour. Administration of delaviridine at 400 mg three times daily resulted in peak plasma concentration of 45 mM. The single dose bioavailability of delaviridine tablets relative to oral solution was approximate 85%. The 50% inhibitory concentration for delavirdine against RT activity was 6.0 nM. Delaviridine is extensively bound to plasma protein (-98%). It is metabolized to its N-desisopropyl metabolite in liver, and the pharmacokinetics is nonlinear. Clarithromycin, rifabutin, or ergot alkaloid derivatives are predicted to increase plasma concentration of delaviridine. Skin rashes are the major side effect of delavirdine therapy. Cross-resistance between delavidine and Pis, such as indinavir, nelfinavir, ritonavir, and saquinavir, is unlikely because of action on different enzyme targets. 

Delavirdine may increase the levels of clarithromycin, whereas efavirenz and nevirapine may reduce clarithromycin levels, and increase those of its hydroxy metabolite. Clarithromycin does not appear to affect the pharmacokinetics of delavirdine, efavirenz or nevirapine to a clinically relevant extent. There is no pharmacokinetic interaction between azithromycin and efavirenz. A case of a neuropsychiatric reaction has been attributed to the use of clarithromycin in a man taking nevirapine. 

In 7 HIV-positive patients clarithromycin 500 mg twice daily for 15 days did not cause a clinically significant change in the pharmacokinetics of delavirdine 300 mg three times daily, when compared with 4 other HIV-pos-itive patients taking only delavirdine. The combination was well tolerated and no serious adverse events occurred. However, although delavirdine levels are unaffected, the manufacturer notes that the AUC of clarithromycin was doubled by delavirdine. ... 

It appears that clarithromycin has minimal effects on the pharmacokinetics of the NNRTIs. However, delavirdine may increase levels of clarithromycin. The manufacturer of delavirdine recommends that when the drugs are used concurrently the dose of clarithromycin should be reduced in pa-... 

Cox SR, Borin MT, Driver MR, Levy B, Freimuth WW. Effect of clarithromycin on the steady-state pharmacokinetics of delavirdine in HIV-1 patients. American Society for Microbiology, 2 National Conference on Human Retroviruses, 1995. Abstract 487. 

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