Didanosine Azoles

Drugs that may affect ritonavir include clarithromycin, didanosine, azole antifungals, nevirapine, SSRIs, St. John s wort, and rifamycins. 

Drugs that may affect nelfinavir include anticonvulsants, azithromycin, azole antifungals, efavirenz, delavirdine, HMG-CoA reductase inhibitors, indinavir, interleukins, nevirapine, rifabutin, rifampin, ritonavir, saquinavir, St. John s wort. Drugs that may be affected by nelfinavir include amiodarone, antiarrhythmics (amiodarone, quinidine), azithromycin, benzodiazepines, efavirenz, ergot alkaloids, delavirdine, didanosine, fentanyl, indinavir, lamivudine methadone, nonsedating antihistamines, oral contraceptives, phenytoin, pimozide, quinidine, rifabutin, saquinavir, sildenafil, sirolimus, tacrolimus, zidovudine. 

Drugs that might affect amprenavir include abacavir, aldesleukin, antacids, anticonvulsants, azole antifungals, clarithromycin, cyclosporine, dexamethasone, buffered didanosine, disulfiram, ethanol, indinavir, methadone, metronidazole, nelfinavir, nonnucleoside reverse transcriptase inhibitors, oral contraceptives, rifamycins, ritonavir, saquinavir, St. John s wort, tacrolimus, and zidovudine. 

Lopinavir/Ritonavir (Kaletra) [Anrirelroviral/Protease Inhibitor] Uses HIV Infxn Action Protease inhibitor Dose Adults. Tx naive 2 tab PO daily or 1 tab PO bid Tx experiencedpt 1 tab PO bid (T dose if w/ amprenavir, efavirenz, fosamprenavir, nelfinavir, nevirapine) Peds. 7-15 kg 12/3 mg/kg PO bid 15-40 kg 10/2.5 mg/kg PO bid >40 kg Adult dose w/ food Caution [C, /-] Numerous interactions Contra w/drugs dependent on CYP3A/CYP2D6 (Table VI-8) Disp Tab, soln SE Avoid disulfiram (soln has EtOH), metronidazole GI upset, asthenia, T cholesterol/triglycerides, pancreatitis protease metabolic synd Interactions T Effects Wl clarithromycin, erythromycin T effects OF amiodarone, amprenavir, azole andfungals, bepridil, cisapride, cyclosporine, CCBs, ergot alkaloids, flecainide, flurazepam, HMG-CoA reductase inhibitors, indinavir, lidocaine, meperidine, midazolam, pimozide, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, tacrolimus, terfenadine, triazolam, zolpidem 1 effects Wl barbiturates, carbamazepine, dexamethasone, didanosine, efavirenz, nevirapine, phenytoin, rifabutin, rifampin, St. John s wort 1 effects OF OCPs, warfarin EMS Use andarrhythmics and benzodiazepines... 

DIDANOSINE AZOLES-ITRACONAZOLE, KETOCONAZOLE Possibly i efficacy of ketoconazole and itraconazole with buffered didanosine Absorption of ketoconazole and itraconazole may be l by the buffered didanosine formulation, which raises gastric pH Give the ketoconazole and itraconazole 2 hours before or 6 hours after didanosine. Alternatively, consider using the enteric-coated formulation of didanosine, which does not have to be given separately... 

For some drugS/ absorption is limited by a compound s solubility/ with dissolution being highly dependent on gastric pH. The antiretroviral agent didanosine/ for example/ is an acid-labile compound/ originally formulated as a buffered preparation to improve its bio availability. Other medications/ such as atazanavir and certain azole antifungals (particularly... 

A sampling of commonly used drugs with cytochrome P450-mediated metabolism inhibited by ketoconazole or other azoles includes chlordiazepoxide, cisapride, cyclosporine, didanosine, fluoxetine, loratadine, lovastatin, methadone, nifedipine, phenytoin, quinidine. theophylline, verapamil, warfarin, and zolpidem. 

Some of the didanosine preparations (e.g. chewable tablets) are formulated with antacid buffers that are intended to facilitate didanosine absorption by minimising acid-induced hydrolysis in the stomach. These preparations can therefore alter the absorption of other drugs that are affected by antacids (e.g. azole antifungals, quinolone antibacterials, tetracyclines). This interaction may be minimised by separating administration by at least 2 hours. Alternatively, the enteric-coated preparation of didanosine (gastro-resistant capsules) may be used. 

Itraconazole capsules and ketoconazole depend on stomach acidity for absorption. A raised gastric pH, caused by the antacids in the buffered didanosine formulation appears to reduce itraconazole absorption (consider, Azoles + Antacids , p.215). The didanosine itself appears to have no part to play in this interaction. The enteric-coated preparation of didanosine does not contain any antacids and therefore does not interact. 

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