Ddl Didanosine

ddI was one of the first NRTIs, which today, because of its side effects (pancreatitis 10 %) and mitochondrial toxicity, is only used in certain resistence situations. The dose has to be adjusted according to body weight.

Combination with tenofovir and d4T should be avoided.

Trade name: Videx™

Enteric coated capsules: 125 mg, 200 mg, 250 mg, 400 mg. Powder: 4 g per bottle. Drug class: NRTI

Manufacturer: Bristol-Myers Squibb Indications: HIV infection

Oral dose: 400 mg qd (body weight > 60 kg) or 250 mg qd (body weight < 60 kg). ddI must be taken on an empty stomach, at least 2 hours after or at the latest 1 hour before meals.

Side effects: diarrhea, nausea, headache. ddI specific: pancreatitis, even after longer periods on treatment! Peripheral polyneuropathy. Rarely: episodes of lactic acido-sis, especially in combination with d4T and ribavirin.

Comments/Warnings: acute and chronic pancreatitis are contraindications, as is treatment with ribavirin! Caution with d4T, ethambutol, cisplatin, disulfiram, INH, vincristine, etc. (PNP).

Concurrent dosing with tenofovir increases the Cmax and AUC of ddI by 28 % and 44 %, respectively. The ddI dose should therefore be reduced to 250 mg. Tenofovir is taken two hours before or one hour after ddI; the two should not be combined at all if possible (see HAART chapter).

With indinavir, dapsone, ketoconazole, itraconazole, or tetracyclines there should be a two-hour interval.

Initially, monthly monitoring of amylase, blood count, transaminases and bilirubin.

Patients should be informed about the risk and signs of pancreatitis. ddI should be discontinued if there is clinical suspicion; avoid rechallenge.

Internet sources:

USA: http://hiv.net/link.php?id=86

References:

1. Leon A, Mallolas J, Martinez E, et al. High rate of virological failure in maintenance antiretroviral therapy with didanosine and tenofovir. AIDS 2005; 19: 1695-7. Abstract: http://amedeo.com/lit.php?id=16184042

2. Martinez E, Milinkovic A, de Lazzari E, et al. Pancreatic toxic effects associated with co-administration of didanosine and tenofovir in HIV-infected adults. Lancet 2004; 364: 65-7. http://amedeo.com/lit.php?id=15234858

3. Moreno A, Quereda C, Moreno L, et al. High rate of didanosine-related mitochondrial toxicity in HIV/HCV-coinfected patients receiving ribavirin. Antivir Ther 2004; 9: 133-8. http://amedeo.com/lit.php?id=15040545

4. Murphy MD, O'Hearn M, Chou S. Fatal lactic acidosis and acute renal failure after addition of tenofovir to an antiretroviral regimen containing Didanosine. Clin Infect Dis 2003; 36: 1082-5. http://amedeo.com/lit.php?id=12684925

Diflucan™ see Fluconazole

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