What is Videx and Videx EC

• Videx and Videx EC are anti-HIV medications. They are in a category of HIV medications called nucleoside reverse transcriptase inhibitors (NRTIs). NRTIs prevent HIV from altering the genetic material of healthy T-cells. This prevents the cells from producing new virus and decreases the amount of virus in the body.

• Videx, manufactured by Bristol-Myers Squibb, was the second drug approved for the treatment of HIV, and was approved by the U.S. Food and Drug Administration in 1989.

• Generic versions of delayed-release didanosine (similar to Videx EC), manufactured by Barr Laboratories, are now available. It was approved by the FDA in December 2004.

• This lesson reviews both Videx buffered tablets, which can be taken once or twice a day, and Videx EC, a capsule that only needs to be taken once a day. They are the same drug, but come in different forms and are taken differently. Because Videx EC is considered to be easier to take and does not contain an antacid buffer (which can cause stomach upsets and prevents many other medications from being taken at the same time as Videx tablets and powder), most HIV-positive adults are now taking Videx EC.

• Videx or Videx EC must be used in combination with at least two other anti-HIV drugs.

What Are the Drug Interactions with Videx EC?

• HIV-positive people must be very careful about using Videx in combination with Viread (tenofovir). There are two important warnings to know about:

• Drug regimens consisting of Sustiva (efavirenz) or Viramune (nevirapine) plus Viread and Videx have been associated with premature drug failure. If you are receiving Viread and Videx EC with either Sustiva or Viramune, you may want to discuss alternative options with your doctor.

• Viread increases the amount of Videx/Videx EC in the body. This can increase the risk of experiencing side effects that can be caused by Videx, such as pancreatitis, peripheral neuropathy, and lactic acidosis. In turn, if Viread and Videx are used together, Videx EC should be taken at a dose of 250mg once a day (reduced from the usual daily dose of 400mg a day).

• Because there are now a number of concerns regarding the use of Viread in combination with Videx/Videx EC, many experts recommend avoiding this combination altogether.

• Ribavirin (Rebetol; Copegus), one of the two drugs that are often prescribed to treat hepatitis C, can increase Videx levels inside cells. Researchers have not yet determined the correct dose of Videx for HIV-positive people who are also taking ribavirin to treat their hepatitis C infection. In turn, it is probably best to avoid combining these drugs.

• Because Videx can cause pancreatitis, it should be used carefully in combination with other drugs that can also cause pancreatitis. These include intravenous pentamidine and TMP/SMX (Bactrim; Septra). It is also possible that combining Videx with hydroxyurea, a cancer drug that has been studied as a treatment for HIV, increases the risk of pancreatitis.

• The oral form of Cytovene (ganciclovir), a treatment used to prevent CMV from recurring in people who have had this disease, can decrease Videx and Videx EC levels in the bloodstream. Videx and Videx EC can increase Cytovene levels in the bloodstream. No dosing recommendations have been made.

• Methadone, a drug frequently used to help people recovering from heroin addiction, can decrease the amount of Videx in the bloodstream. This can result in an anti-HIV drug regimen being less effective against HIV, which can cause drug resistance.

• Combining Videx with Zerit (d4T), another nucleoside reverse transcriptase inhibitor (NRTI), may increase the risk of developing lactic acidosis. This is especially true in HIV-positive pregnant women who take both of these drugs together. In turn, the U.S. Food and Drug Administration (FDA) has recommended that HIV-positive women not take these two drugs together while they are pregnant.

What Are the Drug Interactions with Videx Buffered Tablets?

• Because Videx buffered tablets contain an antacid buffer to neutralize acid in the stomach (this is necessary for Videx to be absorbed properly into the bloodstream), it should not be taken at the same time as medications that require acid in the stomach. Examples of medications that require acid in the stomach include Atrisone (dapsone), Sporanox (itraconazole), Nizoral (ketoconazole), Cipro (ciprofloxacin), and quinolones. These medications should be taken at least two hours before or two hours after taking Videx.

• Videx buffered tablets should not be taken at the same time as any of the available protease inhibitors, especially Reyataz (atazanavir). The protease inhibitors should be taken at last two hours before or two hours after taking Videx.

• Videx buffered tablets can be taken at the same time as Viramune (nevirapine) and Sustiva, two non-nucleoside reverse transcriptase inhibitors (NNRTIs). Rescriptor (delavirdine), another NNRTI, should be taken two hour before or two hours after taking Videx.

• Methadone, a drug used to treat heroin addiction, can decrease the amount of Videx (from the buffered tablets only) in the bloodstream. As a result, it's probably best to switch from Videx buffered tablets to Videx EC capsules if methadone is also being used.

Adverse Events / Toxicity / Side Effects

• Pancreatitis
Pancreatitis, which has been fatal in some cases, is one of the most serious adverse effects reported in patients receiving didanosine. The frequency of pancreatitis is dose-related, with an incidence in adult patients between 1% and 7% and in pediatric patients between 3% and 13%. Pancreatitis has occurred during didanosine therapy in both treatment-experienced and treatment-naive patients, regardless of the degree of immunosuppression. Didanosine treatment should be suspended in patients with suspected pancreatitis and discontinued in patients with confirmed pancreatitis.

• Lactic Acidosis and Hepatomegaly
The use of didanosine and other nucleoside analogues, either alone or in combination with other antiretrovirals, has been associated with lactic acidosis and severe hepatomegaly with steatosis, including some fatal cases. Risk factors include female gender, obesity, and prolonged exposure to antiretroviral nucleoside analogues.

Fatal lactic acidosis has been reported in pregnant women who received an antiretroviral regimen that included didanosine and stavudine. Cases have occurred in patients with and without known risk factors for liver disease.

Didanosine use should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity, which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations.

• Peripheral Neuropathy
Peripheral neuropathy, manifested by numbness, tingling, or pain in the hands or feet, has been reported in patients taking didanosine. In recent studies, peripheral neuropathy was reported in 21% to 26% of patients taking didanosine in conjunction with stavudine (d4T, Zerit) and either nelfinavir (Viracept, and HIV protease inhibitor) or indinavir (Crixivan, and HIV protease inhibitor.

• Common, less serious adverse effects include central nervous system effects (anxiety, headache, insomnia, irritability, and restlessness); dry mouth; gastrointestinal disturbances (diarrhea, dyspepsia, flatulence, nausea, vomiting); and skin rash.

• Other, less frequently reported, effects involve the following organ systems: body as a whole (alopecia, anaphylactoid reaction, asthenia, chills/fever, pain, redistribution/accumulation of body fat); cardiovascular (cardiomyopathy); exocrine (sialoadenitis, parotid gland enlargement, dry mouth); hematologic (anemia, leukopenia, thrombocytopenia); metabolic (hyperglycemia, hypoglycemia, diabetes mellitus); musculoskeletal (myalgia, rhabdomyolysis with acute renal failure, arthralgia, myopathy); and ocular (retinal changes, optic neuritis, diplopia, dry eyes, optic atrophy, and blindness).