Itraconazole Didanosine

Drugs that may affect itraconazole include antacids, carbamazepine, didanosine, H2 antagonists, hydantoins, macrolide antibiotics, nevirapine, phenobarbital, phenytoin, protease inhibitors, proton pump inhibitors, and rifamycins. 

Drugs that may affect atazanavir include the following antacids and buffered medications, clarithromycin, didanosine (buffered formulation only), efavirenz, H2-receptor antagonists, indinavir, itraconazole, ketoconazole, nevirapine, proton pump inhibitors, rifampin, ritonavir, St. John s wort, tenofovir, voriconazole. 

Itraconazole has significant interactions with a number of commonly prescribed drugs, such as rifampin, phenytoin, and carbamazepine. Itraconazole raises serum digoxin and cyclosporine levels and may affect the metabolism of oral hypoglycemic agents and coumadin. Absorption of itraconazole is impaired by antacids, Hj blockers, proton pump inhibitors, and drugs that contain buffers, such as the antiretroviral agent didanosine. 

The buffer in didanosine tablets and powder interferes with absorption of indinavir, delavirdine, atazanavir, dapsone, itraconazole, and fluoroquinolone agents therefore, administration should be separated in time. Serum levels of didanosine are increased when -administered with tenofovir or ganciclovir, and are decreased by atazanavir, delavirdine, ritonavir, tipranavir, and methadone (Table 49-4). 

The original formulation, a buffered powder, has been replaced by chewable and dispersible buffered tablets with greater bioavailability (30-40%) a new enteric-coated formulation further improves patient convenience and tolerability. Since the chewable tablets contain both phenylalanine (36.5 mg) and sodium (1380 mg), caution should be exercised in patients with phenylketonuria and those taking sodium-restricted diets. Didanosine should be taken on an empty stomach and, because of the buffered formulation, should be administered at least 2 hours after administration of drugs requiring acidity for optimal absorption (eg, ketoconazole, itraconazole, dapsone). 

ITRACONAZOLE, KETOCONAZOLE DIDANOSINE Possibly 1 efficacy of ketoconazole and itraconazole with buffered didanosine Absorption of the 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... 

Didanosine (ddl) Videx.Videx- Videx 100 mg 150 mg 200 mg 25 mg 50 mg tablets. Cefpodoxime, cefuroxime, ketoconazole, itraconazole. 

Abacavir Adinazolam 5-Aminosalicylic acid Atorvastatin Avitriptan Bromazepam Bumetanide Celecoxib CGP 43371 Clodronate Cyclosporin Danazol Didanosine Erythromycin Fexofenadine Furosemide Ganciclovir Halofantrine Inidnavir Itraconazole Levofloxacin Methotrexate Nifedipine Pravastatin Rifabutin Stavudine Tacrine... 

May DB, Drew RH, Yedinak KC, Bartlett JA. Effect of simultaneous didanosine administration on itraconazole absorption in healthy volunteers. Pharmacotherapy 1994 14(5) 509-13. 

Itraconazole appears not to affect the pharmacokinetics of zidovudine. Serum levels of itraconazole are markedly reduced when buffered didanosine is given at the same time, but itraconazole and ketoconazole are not affected if buffered didanosine is given 2 hours later. Enteric-coated didanosine has no clinically relevant effect on the pharmacokinetics of flnconazole, itraconazole or ketoconazole. The frequency of haematological toxicity with zidovudine was not increased by ketoconazole. 

Enteric-coated preparation. Enterie-eoated didanosine 400 mg had no significant effect on the pharmacokinetics of fluconazole 200 mg in 14 healthy subjects, and no clinically relevant effect on the pharmacokinetics of itraconazole 200 mg in 25 healthy subjects. Similarly, enteric-coated didanosine 400 mg had no clinically relevant effect on the pharmacokinetics of ketoconazole 200 mg in 24 healthy subjects. Three of the subjects had increased concentrations of ketoconazole with didanosine, but their... 

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. 

The most significant interaction occurs between the buffered preparation of didanosine and itraconazole. Patients should avoid taking both drugs at the same time, but giving the itraconazole at least 2 hours before the didanosine appears to solve any problem. Any possible interaction with ketoconazole can similarly be avoided by giving ketoconazole at least 2 hours before didanosine. Alternatively, the interaction may be avoided by using the enteric-coated preparation of didanosine. 

Moreno F, Hardin TC, Rinaldi MG, Graybill JR. Itraconazole-didanosine excipient interaction. J.4A (1993) 269,1508. 

Hardin TC, Sharkey-Mathis PK, Rinaldi MG, Graybill JR. Evaluation of the pharmacokinetic interaction between itraconazole and didanosine in HIV-infected subjects. Intersci ConfAn-timicrob Agents Chemo er (1995) 35,6. 

Damle B, Hess H, Kaul S, Knupp C. Absence of clinically relevant drug interactions following simultaneous administration of didanosine-encapsulated, enteric-coated bead formulation with either itraconazole or fluconazole. Biopharm Drug Dispos (2002) 23, 59-66. 

Simultaneous didanosine, folic acid, ganciclovir, lamivudine, nevirapine, pyrazinamide, ranitidine, rifampin, stavudine, sulfamethoxazole, trimethoprim, zidovudine Noninterfering adefovir, amprenavir, delavirdine, efavirenz, fluconazole, indinavir, itraconazole, methadone, nelfinavir, oxazepam, pyrimethamine, rifampin, ritonavir, saquinavir, zalcitabine... 

Noninterfering acetaminophen, amineptine, amphotericin B, aspirin, bromazepam, buspirone, citalopram, clobazam, diazepam, didanosine, fluconazole, flunitrazepam, flu-voxamine, hydroxyitraconazole, isoniazid, itraconazole, lamivudine, loprazolam, lora-zepam, metronidazole, minalcipram, nordiazepam, omeprazole, paroxetine, pyrimethamine, rifampin, sertraline, stavudine, sulfadiazine, trimethoprim, venlafaxine, zal-citabine, zidovudine, zolpidem, zopiclone... 

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