Didanosine

Didanosine tablets are round and off-white to pale yellow-orange, with "Videx" on one side and the tablet strength on the other side. Didanosine is also available in a powder form for oral solution. Dosing may vary.

"The study showed that patients who switched treatments from AZT to 500 mg of ddI had significant delays in the rate of AIDS-defining illness or death.... However, we found among patients who entered the study with AIDS, there were no differences according to treatment group. The three treatment groups had the same survival rates."

National Institute of Allergy and Infectious Diseases (NIAID) August 26, 1992

"Because there was no survival advantage from switching from AZT to DDI to treat HIV infection, it cannot be considered effective."

AIDS Daily Summary (review of The Lancet 341:8844, p. 570, 1993)

Also known as: ddI

Background and description. Didanosine was approved by the US Food and Drug Administration (FDA) in October 1991. The drug is a nucleoside reverse transcriptase inhibitor (NRTI), manufactured and distributed by Bristol-Myers Squibb. In 1999 the FDA revised didanosine's package insert to reflect its inclusion as a first-line component of combination antiretroviral HIV therapy.

Guidelines classification. The Panel on Clinical Practices for the Treatment of HIV Infection classifies didanosine as "strongly recommended" when used with stavudine (Zerit) or zidovudine (Retrovir).

Dose. Didanosine was initially approved for twice a day dosing, but since October 1999 once a day dosing is available. Tablets are chewable or dispersible in water and dosing is weight-dependent. For patients weighing greater than or equal to 132 lb, a dose of 400 mg once a day or 200 mg twice a day of didanosine is recommended (200 mg tablets are only to be used in once-daily dosing; two tablets equaling a full-dose should be ingested each time to ensure adequate buffer intake). For patients in this weight group, a dose of 250 mg twice a day of didanosine powder can be used as well. For patients weighing less than 132 lb, a dose of 250 mg once a day or 125 mg twice a day is recommended (at least 2 tablets at each dose); 167 mg twice a day of didanosine powder can also be used. Special dosing adjustments are necessary in patients with renal impairment. Patients with peripheral neuropathy may require lower doses.

Food restrictions. Didanosine should be administered on an empty stomach (either 30 minutes before or 1-2 hours after a meal). Bristol-Myers Squibb has filed an application with the FDA for an enteric-coated tablet, which would remove food restrictions; it is scheduled for release in the third quarter of 2000.

Storage. Tablets should be kept in tightly closed containers. Both tablets and powders may be stored at 59 [degrees] to 86 [degrees] F. If tablets are dispersed in water, the mixture may be kept for 1 hour at room temperature. When dissolving the powder for oral solution, the mixture can be kept at room temperature for up to 4 hours.

Side effects and toxicity. Didanosine is associated with the following side effects: pancreatitis, peripheral neuropathy, vision changes (retinal depigmentation or optic neuritis), nausea and diarrhea. Lactic acidosis and severe hepatomegaly (enlarged liver) with steatosis (fatty liver) are rare, but potentially fatal, and have been associated with NRTI use. As a class, NRTIs have been implicated in damage to mitochondrial DNA and may therefore play a role in the development of metabolic and morphologic abnormalities.

Drug interactions. Drugs known to cause or contribute to pancreatitis, including alcohol, should be used with caution when administering didanosine. Antacids containing magnesium or aluminum may cause adverse side effects if given concomitantly with didanosine tablets. Drugs affected by levels of stomach acidity like ketoconazole (Nizoral) or itraconazole (Sporanox) should be taken at least 2 hours prior to didanosine. Didanosine should be taken 2 hours after or 6 hours before ciprofloxacin (Cipro); caution should be taken with other quinolone antibiotics as well. Methadone (Dolophine) can decrease didanosine levels up to 41% (methadone levels remain unchanged): increased dosing of didanosine should be considered. Delavirdine (Rescriptor) and indinavir (Crixivan) should be given 1 hour before didanosine. Nelfinavir (Viracept) can be administered with a light meal 1 hour after didanosine. Didanosine is not recommended for use with zalcitabine (Hivid).

Resistance and cross-resistance. Didanosine resistance is associated with mutations at positions 65 and 74. The mutation at 74 is more common. A mutation at position 151 is associated with resistance to the entire NRTI class. An insertion at position 69 can also lead to broad NRTI resistance.

Clinical data. Although clinical studies showing marginal efficacy of didanosine monotherapy were used to get approval for the drug's registration, monotherapy is no longer considered optimal use of this or any antiretroviral drug. Studies A1454-148 and START 2, using combination therapy with dual NRTIs and a protease inhibitor, have shown that didanosine performs well in combination with other antiretroviral drugs in lowering viral load below 400 copies/mL and increasing CD4 T cell counts.

Patient assistance. For those who qualify, Bristol-Myers Squibb offers a patient assistance program. For more information, call 800.272.4878.

COPYRIGHT 2000 The Center for AIDS: Hope & Remembrance Project
COPYRIGHT 2000 Gale Group