March/April 2009
Common Name: didanosine or ddI
Brand Name: Videx & Videx EC
Class: nucleoside analog (also called nucleoside reverse transcriptase inhibitor, NRTI or nuke)
Standard dose: One 400 mg enteric-coated (Videx EC) delayed-release capsule once a day, with adjustments for weight and when combined with Viread, Truvada, or Atripla. (Also available in 125 mg, 200 mg and 250 mg capsules.) Videx is also available as a buffered powder for oral solution. Take Videx and Videx EC strictly on an empty stomach (unless taking with Viread), one hour before or two hours after food or drink, except water. A reduced dose may be needed for people with kidney problems. Approved for children weighing at least 44 pounds. Take missed dose as soon as possible, but do not double up on your next dose. Generic Videx EC is available.
AWP: $426.10 for Videx EC (generic enteric-coated $368.72) / month
Manufacturer contact: Bristol-Myers Squibb,
www.bmsvirology.com, 1 (800) 272-4878
AIDSInfo:
1 (800) HIV-0440 (448-0440), www.aidsinfo.nih.gov
Potential side effects and toxicity: Peripheral neuropathy (tingling, burning, numbness or pain in the hands or feet) may go away once ddI is stopped, but can be painful and permanently debilitating if not treated in time and occurs more frequently when used with Zerit. Upset stomach, diarrhea, headache, and more rarely pancreatitis (inflammation of the pancreas) have also been reported. Other possible toxicities include eye changes and optic neuritis. Have periodic eye exams by someone who is aware you are HIV-positive. Increased uric acid levels (indicating a number of disorders, including kidney damage and metabolic diseases), and insomnia are other potential side effects. Rare but potentially fatal toxicity with all NRTIs: hepatomegaly with steatosis (enlarged fatty liver) and lactic acidosis (accumulation of lactate in the blood and abnormal acid-base balance). Lactic acidosis has been seen in patients taking NRTIs, but is more common and more severe in women, people who are obese, and people who have been taking NRTIs for a long time; it is more common in people with liver disease, but can occur in people without a history of liver damage. People with lactic acidosis may experience persistent fatigue, abdominal pain or distension, nausea/vomiting, difficulty breathing or shortness of breath, and enlarged, fatty liver. People with a history of peripheral neuropathy, pancreatitis, or heavy alcohol use should avoid ddI. Pancreatitis can be life-threatening and may cause pain in the stomach and back, along with nausea, vomiting, and bleeding. Risks for pancreatitis include higher than recommended doses of NRTIs, advanced HIV, and alcohol use. Stop all HIV medications and see a health care provider right away. Body fat redistribution/accumulation has also been reported with ddI.
Potential drug interactions: The levels of ddI are increased by 44-60% when taken at the same time as Viread, therefore a dose reduction to 250 mg for Videx is recommended if you weigh more than 60 kg (132 pounds). The combined use of ddI and Retrovir (zidovudine, AZT) or hydroxyurea may increase risk of peripheral neuropathy. Combining ddI with Zerit or with hydroxyurea, alcohol, ganciclovir, valganciclovir, or intravenous (not inhaled) pentamidine may increase risk of pancreatitis. Also, ganciclovir and ribavirin substantially increase ddI levels, and are generally recommended not to be taken together. Didanosine oral solution should be taken on an empty stomach two hours apart from protease inhibitors, Tagamet (cimetidine), ketoconazole, itraconazole, and dapsone, and one hour apart from Rescriptor, while Videx EC can be taken with them, but still on an empty stomach. With Viread, it may be taken with a light snack (low-fat, 373 calories). The dose of ddI may need to be increased when taken with methadone.
Tips: Study indicates Videx EC (compared to Videx) may have lower risk of peripheral neuropathy. Either drug taken with Zerit increases the risk of facial wasting, or lactic acidosis. Swallow the capsules whole. The capsules eliminate the bad taste and texture of the tablets and the enteric coating reduces diarrhea. If you have reduced kidney function, you may require a lower dose. Notify your doctor right away if peripheral neuropathy is suspected. Please see package insert for more complete potential side effects and interactions.
Doctor
Videx (didanosine, known to most as ddI) was approved for use in HIV infection in 1991. This was the second antiretroviral drug produced and those who failed AZT were started on Videx. This trend of sequential monotherapy continued for several years before we understood that combination therapy (HAART) was more potent and durable. The unfortunate fallout from this was the emergence of multi-resistant virus in those who survived, and death for many who had untreatable resistant virus. Videx is poorly absorbed in the gut and was first formulated in a chewable tablet containing antacid to increase absorption. I can vividly remember the chewable tablets -- most patients hated chewing up to 4 tablets two times daily. I made all health care workers who rotated through our clinic chew a placebo Videx tablet (including me, ugh!). This forever imprinted in their memory what patients had to do twice daily and on an empty stomach. In 2000, BMS formulated and patented a Videx EC capsule. This dosing formulation replaced the chewable tablets. Dosing is now one capsule daily (dose dependent on weight and kidney function), but the dietary restriction remains. A generic form of Videx capsules was also approved for sale in the U.S. in 2004. Videx is a very difficult drug to use. In addition to the dietary restrictions, neuropathy, hepatitis, pancreatitis, and lipodystrophy changes accompany the use of this drug. Combining it with stavudine [Zerit] enhances the occurrence of all of the above. Early on, when tenofovir [Viread] first came out, we learned the hard way (severe patient morbidity) that the dose of Videx had to be reduced when used with tenofovir. An increased risk of myocardial infarction (heart attack) was found with current use of Videx (as seen with abacavir) in the D.A.D. observational study. Videx use in our clinic is currently minimal. Some stalwart patients continue it to this day. They fear failure with other antiretrovirals. Occasionally, we will use Videx (if we can show it has activity) in those needing a second, third, or fourth drug in salvage therapy. In developing countries, ddI continues to be an important component of HAART therapy (especially in Africa). All the adverse effects of the drug are observed and often the chewable tablets are the only dosage form available. -- Frank M. Graziano, M.D., Ph.D.
Activist
Videx was once a major player with the anti-HIV drugs, but now it's pretty much just a benchwarmer, only being called into play when nothing else seems to be working. The early version was just plain nasty -- both in terms of taste and side effects. The new, improved "enteric-coated" version only eliminated the antacid buffer, improving the taste aspect and making it easier to take, but the major side effects of peripheral neuropathy and pancreatitis remain. The neuropathy can be painfully debilitating and the pancreatitis, acute and deadly. And like its early counterpart AZT, Videx is associated with mitochondrial toxicity and can cause lactic acidosis, a buildup of lactic acid in the blood resulting from abnormal production of energy within a cell. Videx also has significant drug-drug interactions, particularly with Viread, and should be taken in a smaller dose than the usual 400 mg enteric-coated capsule when used with Viread. -- Morris Jackson