Ketoconazole Didanosine

Azithromycin, fluoroquinolones, ketoconazole, isoniazid, penicillin, rifampin, and tetracycline ° Didanosine, indinavir, stavudine, and zidovudine ° Aledronate, risedronate, and levodopa... 

Drugs that may affect ketoconazole include antacids, didanosine, histamine H2 antagonists, isoniazid, sucralfate, proton pump inhibitors, and rifampin. Drugs that may be affected by ketoconazole include oral anticoagulants, corticosteroids, cyclosporine, protease inhibitors, tricyclic antidepressants, carbamazepine. 

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. 

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

Buffering agents that are compounded with didanosine to counteract its degradation by gastric acid may interfere with the absorption of other drugs that require acidity (e.g., indinavir, delavirdine, ketoconazole, fluoroquinolones, tetracyclines, dapsone). An enteric-coated formulation Videx EC) that dissolves in the basic pH of the small intestine is not susceptible to these interactions. Ganciclovir and valganciclovir can increase blood levels of didanosine. The use of zalcitabine with didanosine is not recommended because that combination carries an additive risk of peripheral neuropathy. The combination of didanosine with stavudine increases the risk of pancreatitis, hepatotoxicity, and peripheral neuropa-... 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

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). 

Adverse effects Pancreatitis, which may be fatal, is a major toxicity of ddl treatment, and requires monitoring of serum amylase. The dose-limiting toxicity of didanosine is peripheral neuropathy. [Note The buffering of stomach contents may interfere in the absorption of other drugs that require an acidic milieu for absorption, such as ketoconazole.]... 

Damle BD, Mummaneni V, Kaul S, Knupp C. Lack of effect of simultaneously administered didanosine encapsulated enteric bead formulation (Videx EC) on oral absorption of indinavir, ketoconazole, or ciprofloxacin. Antimicrob Agents Chemother 2002 46(2) 385-91. 

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. 

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. 

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. 

Twelve HIV-positive patients were given buffered didanosine 375 mg twice daily either alone or 2 hours after ketoconazole 200 mg daily, for 4 days. Didanosine maximum plasma levels were slightly redueed by 12% and no significant changes in the pharmaeokineties of the ketoconazole were seen when dosing was separated in this way. ... 

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. 

Knupp CA, Brater DC, Relue J, Barbhaiya RH. Pharmacokinetics of didanosine and ketoconazole after coadministration to patients seropositive for the human immunodeficiency virus. J Clin Pharmacol (1995) 33, 912-17. 

---