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Drugs! Drugs! Drugs!
An Overview of the Approved Anti-HIV Medications

Videx, Videx EC (ddI, Didanosine, Dideoxyinosine)

Fall 2003/Winter 2004

Videx was the second anti-HIV drug approved by the FDA. Its approval in October 1991 was unique in that it was the first time that a drug was approved based on surrogate markers such as lab results (in this case, increased CD4 cells) rather than on clinical endpoints such as disease progression or survival. Much has been learned about Videx since then, including data from trials that looked at clinical endpoints. The drug has been researched in various combinations and populations and gone through many formulations and dosing schedules. There's much to say both for and against it, but it remains useful for many people and in a variety of triple-drug combinations.


People have put up with Videx for years -- chewing the huge, horrible tasting tablets, crushing them and mixing them in water, or dissolving a powdered version into water twice a day. Videx has to be taken on an empty stomach because the drug can't be absorbed properly in an acidic setting, including stomach acid. The original versions of Videx (the tablets and powder) contain a buffer to reduce stomach acid, which means that they can't be taken with many other anti-HIV medications that require acid in the stomach to be absorbed properly. The approval of Videx EC (enteric coated) time-release capsules in October 2000, was a big improvement -- once-a-day dosing (although still on an empty stomach) and no buffer, which cut down on the diarrhea that the buffer caused and allowed Videx to be taken at the same time as other medications. Most people who use the drug now take Videx EC.


Researchers at the National Cancer Institute (NCI) first identified Videx's potential as a treatment for HIV in 1985. The NCI began the first clinical trial of Videx in 1988, and then licensed the drug to Bristol-Myers Squibb on an exclusive basis. Early studies showed that taking Videx alone was slightly better than taking Retrovir (AZT) alone, particularly for people who had already taken Retrovir.

The first study to show that Videx had a positive effect on slowing disease progression was ACTG 116-B/117. The study assigned 913 people who had taken Retrovir alone for at least four weeks (an average of 13 _ months) to continue Retrovir or to switch to one of two doses of Videx (500 or 750 mg a day). After 55 weeks, those who switched to the lower dose of Videx had significantly lower rates of opportunistic infections or death (32%) compared to those who switched to the higher dose of Videx (37%) or those who stayed on Retrovir (41%). People in the trial who took Videx lost fewer CD4 cells than those who stayed on Retrovir. These results, reported in the New England Journal of Medicine in August 1992, led the FDA to recommend that Videx be prescribed at lower doses than had originally been approved.

Throughout the early '90s, many studies showed the effectiveness of Videx as monotherapy and as part of two-drug combinations (see discussions of ACTG 175 and the Delta study in the Hivid section). Lots of people began to use Videx instead of Retrovir as monotherapy, switched back and forth between the two, or started two-drug combination therapy with both. As trials were designed to study protease inhibitors and non-nucleosides in three-drug combinations, it became more difficult to assess the comparative effectiveness of the individual NRTIs.

In the mid to late '90s, there was a lot of excitement about the possibility of combining Videx (and sometimes Zerit [d4T] or both) with hydroxyurea to boost the activity of Videx. Hydroxyurea has been around for over thirty years and is used to treat certain cancers and sickle cell anemia at higher doses than were used in the HIV research. Hydroxyurea itself doesn't slow down HIV replication, but changes a cellular enzyme in such a way that HIV's reverse transcriptase enzyme can't transcribe its RNA into DNA. In test tube (in vitro) and small human studies, hydroxyurea seemed to enhance the antiviral activity of Videx, even against HIV that was resistant to Videx. Unfortunately, larger studies, particularly ACTG 5025, which involved 200 participants, showed that adding hydroxyurea to a combination increased toxic side effects (more peripheral neuropathy and, particularly, pancreatitis) without increasing CD4 cells. The study was shut down prematurely in September 1999 because of two deaths from pancreatitis in the arm of the study that added hydroxyurea. Research into hydroxyurea as a way to boost the effectiveness of Videx essentially stopped, and hydroxyurea is rarely used in clinical practice today.

Confusion about the dosage of Videx was complicated further in October 1999 when the FDA approved a version of buffered Videx to be taken as two tablets once a day. The new version made Videx the first nucleoside analog approved for once-daily use. Unfortunately, in August 2000 Bristol-Myers Squibb (BMS) had to send a letter to healthcare providers saying that Videx should be taken twice a day after all. The once-a-day dose was called into question when a study of over 750 people who had never taken anti-HIV therapy before indicated that, after a year, the people on the combination that included once-a-day Videx had significantly higher viral loads than those on the other regimen. The approval in 1999 had been based on six-month results of the same trial. Videx EC, the capsule formulation, was approved for once-a-day use only a few months after BMS' letter went out, so Videx still became the first nucleoside analog approved for once-daily use.

Videx EC capsules are at least as effective and have fewer side effects and interactions with other drugs than the old Videx buffered tablets taken either once or twice a day.

Side Effects

Less serious side effects of Videx include diarrhea (especially with the tablet and powder forms), chills or fever, rash, abdominal pain, weakness, headache, nausea, vomiting, decreased appetite, dry mouth, and dry eyes. Unfortunately, Videx can also cause far more serious side effects -- peripheral neuropathy (tingling, pain, and numbness in the feet and hands), pancreatitis (inflammation of the pancreas), and vision changes.

Peripheral neuropathy occurs in as many as 20% of people who take Videx. If the drug isn't stopped, the neuropathy can be irreversible, resulting in permanent nerve damage. Videx-related pancreatitis occurs in 1-7% of patients and usually takes a few months to develop. Symptoms of pancreatitis can include nausea, vomiting, diarrhea, blood in the urine, and sharp pain in the back or upper abdomen. If you experience these symptoms while on Videx, contact your healthcare provider immediately. Pancreatitis can be fatal. If you have to stop taking Videx because of pancreatitis, don't take the drug again. Very rarely, Videx can affect the nerves in the eyes, especially in children. If you're on Videx, getting an exam by an HIV-experienced ophthalmologist (eye doctor) every four to six months is an important part of your care.

The risk of peripheral neuropathy or pancreatitis can be increased by other factors, including advanced HIV disease and a history of either condition. If you're on another drug that also has peripheral neuropathy as a possible side effect, such as Zerit, amphotericin B, Foscavir (foscarnet), dapsone, or vincristine, be sure that you're monitored closely for symptoms.

Heavy alcohol use can increase the risk of pancreatitis, so if you're a heavy drinker, avoid either alcohol or Videx. Other drugs that may increase the risk of pancreatitis include Cytovene (oral ganciclovir), rifampin, and Mycobutin (rifabutin).

Drug Interactions

In addition to drugs that can increase the likelihood of side effects, many other drug interactions are possible with Videx. The older tablet and powder versions have more drug interactions because of the buffer.

  • Tablets or Powder: Nizoral (ketoconazole), Sporanox (itraconazole), dapsone, and other drugs that are affected by stomach acid should be taken at least two hours before Videx. Videx shouldn't be taken within two hours of the antibiotics tetracycline, doxycycline, or minocycline because Videx lowers the amount of antibiotic that gets into your system. Videx should be taken at least two hours after or six hours before Cipro (ciprofloxacin). Be careful with other quinolone antibiotics as well. Videx and the protease inhibitor Crixivan (indinavir) need to be taken at least one hour apart and both on an empty stomach. The NNRTI Rescriptor (delavirdine) should be taken one hour before taking Videx. Antacids that contain magnesium or aluminum (Rolaids, Maalox, Milk of Magnesia, and others) may cause more serious side effects if taken with Videx.

  • Capsules: Many of the interactions that are caused by the buffer in the tablet and powder formulations aren't a problem with the Videx EC capsules. These include the interactions with Nizoral, Sporanox, Crixivan, dapsone, Cipro, and other antibiotics. Videx EC can be taken at the same time as these medications.

  • All Formulations: Methadone decreases Videx levels by as much as 40%, so the amount of Videx getting into your system may not be enough to do its job. Increasing your Videx dose may be necessary. Videx doesn't decrease methadone levels.

    Viread (tenofovir) significantly increases levels of Videx in the blood, which could cause more severe side effects. If Viread is combined with Videx, some research suggests that the Videx dose should be reduced to one 250-mg Videx EC capsule once a day. This dose is still experimental and hasn't been recommended for use in combination with Viread by the FDA.

    Ribavirin, used for the treatment of hepatitis C, should not be used with Videx. People taking both drugs have a much greater likelihood of developing Videx-related side effects, particularly pancreatitis.

When to Consider It

The challenge of taking Videx on an empty stomach and the possibility of serious side effects make it less-than-ideal when faced with choosing the best nucleoside analogs for a first combination. Videx is included in only two of the 21 preferred or alternative regimens that the recently revised Department of Health and Human Services treatment guidelines recommend for people who have never taken antiretrovirals before. Recent research has shown promising results using Videx as part of a first-line regimen, particularly in combination with Epivir (3TC), so that recommendation may change in the future. Videx's once-daily dosing gives the drug an advantage over many other nucleoside analogs if you're trying to come up with an entire once-a-day regimen. Videx resistance takes a long time to develop and is unlikely to cause cross-resistance to Retrovir or Zerit, another plus for early use.

But Videx may be more useful later, after earlier regimens have failed. Resistance testing, particularly phenotypic testing, may be helpful in such situations since the resistance profile of Videx is complicated and not entirely clear. Videx is active against HIV that's resistant to Epivir, another argument for saving Videx for later use.

Good to Know

  • Because of the empty stomach requirement, many people find that taking Videx just before going to bed works best.

  • Avoid the combination of Videx and Hivid (ddC). Both can cause neuropathy and pancreatitis, they have similar resistance profiles, and they don't work well together anyway.

  • Your Videx dose may need to be reduced if you have kidney problems.


Videx is classified as an FDA pregnancy category B drug, meaning that animal reproduction studies don't show a risk to the fetus and adequate, well-controlled studies of pregnant women haven't been conducted. High doses of Videx given to pregnant rats, mice, and rabbits haven't resulted in problems to the development of the fetus. A small study (PACTG 249) of fourteen HIV-positive pregnant women who took Videx during their third trimester and for six weeks after giving birth showed no negative effects on the women or their fetuses. But the FDA and Bristol-Myers Squibb issued a warning that pregnant women may be at increased risk of fatal lactic acidosis when prescribed a combination that includes Videx and Zerit. These drugs should only be prescribed together for pregnant women if the potential benefit clearly outweighs the potential risk.


Because of its many formulations, Videx dosing is arguably the most complicated of any antiretroviral. The adult dose of both the original buffered version and the newer capsules is based on weight. All formulations of Videx need to be taken on an empty stomach. For best absorption, take your dose at least ½ hour before or 2 hours after eating. Absorption of Videx can be decreased by as much as 50% if the drug is taken with food, which would leave you with too little drug in your system to do its job.

  • Videx EC capsules are taken once a day. Capsules are available in 125, 200, 250, and 400-mg versions. People who weigh 60 kg (132 pounds) or more take one 400-mg capsule once a day; those who weigh less than 132 pounds take one 250-mg capsule once a day. After studying the research, the United Kingdom's HIV Pharmacy Association expanded the food restriction, recommending that you not eat anything (or drink anything but water) 2 hours before and 2 hours after taking Videx EC.

  • Videx tablets are available in 25, 50, 100, 150, and 200-mg versions. They are chewed or crushed and mixed in an ounce or more of water (adding apple juice or using apple juice instead of water can help relieve the awful taste). People who weigh 132 pounds or more take 200 mg twice a day; those who weigh less than 132 pounds take 125 mg twice a day. To achieve the required buffering, take at least two but no more than four tablets to make up your necessary dose -- for example, if your dose is 200 mg twice a day, use two 100 mg or four 50 mg tablets each time. The 200-mg tablets are only for once-a-day dosing, which is not generally recommended. If an unusual situation warrants once-daily use of this formulation, the dose is 400 mg for people who weigh 132 pounds or more and 250 mg for those who weigh less than 132 pounds.

  • Videx buffered powder comes in single-dose packets of 100, 167 and 250 mg. The powder is mixed in four ounces of water -- water only, don't add apple (or any other) juice! People who weigh 132 pounds or more take 250 mg twice a day; those who weigh less than 132 pounds take 167 mg twice a day. The powder can't be used for once-daily dosing.

  • The pediatric dose of Videx for children ages 2 weeks to 8 months is 100 mg per meter squared (m2) of body surface area twice a day; the dose for children older than 8 months is 120 mg/m2 twice a day. A pharmacist, mixing Videx powder with purified water and antacid, prepares the pediatric formulation. Videx EC is not approved for pediatric use.

FDA Approval: Videx 1991; Videx EC 2000

Manufacturer: Bristol-Myers Squibb

Patient Assistance Program: 877-758-7877

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This article was provided by AIDS Community Research Initiative of America. It is a part of the publication ACRIA Update. Visit ACRIA's website to find out more about their activities, publications and services.