Taking it

ddI (didanosine, Videx / VidexEC) is available in tablet and in capsule form. The tablets and capsules have slightly different dosing instructions. It is important that patients take the drug as prescribed in order to maintain adequate levels of ddI in the blood.

The original formulation of ddI is as large white, mandarin-flavoured tablets. The tablets, which are marketed as Videx, should be chewed, crushed or dispersed in water or clear apple juice before they are taken. They should not be swallowed whole, or dissolved in acidic drinks like cola or orange juice.

A pill crusher may help patients dissolve the tablets. They can also be dissolved in the evening and left in the refrigerator overnight if the dose is taken first thing in the morning.

The tablets must be taken at least two hours after and 30 minutes before food. However, patients should wait four hours before taking ddI if they have eaten a large meal, such as a three-course dinner. Patients should also avoid acidic juices, carbonated drinks and milk during the fasting period.

The tablets contain an antacid buffer, which protects the drug from inactivation by acid in the stomach. In 2000, Bristol-Myers Squibb introduced ddI tablets containing less buffer.

Tablets are available in strengths of 25, 50, 100, 150 and 200mg. To ensure adequate buffering of stomach acids, at least two tablets should be taken to make up each dose. However, no more than four tablets should be taken at once, to avoid gastro-intestinal side-effects.

Smoking induces stomach acid, which may reduce the effectiveness of ddI. Reducing or avoiding smoking after taking a ddI dose is advised.

The original dose of ddI tablets was 200mg twice a day in people over 60kg, or 125mg twice a day in people weighing less than 60kg. However, once-daily dosing of ddI tablets was approved in the European Union in May 1999 and by the United States authorities in October 1999, following evidence that the two doses were of similar efficacy.^{1 2} The recommended once-daily dose is 400mg for people over 60kg and 250mg for people under 60kg.

However, following this approval, the United States Food and Drug Administration issued a warning in August 2000 stating that the preferred dosage of ddI is twice daily, after a triple-drug combination including once-daily ddI was found to be less effective than one including AZT (zidovudine, Retrovir) and 3TC (lamivudine, Epivir).³ European regulators have not issued a similar warning about once-daily ddI. Bristol-Myers Squibb has argued that the inferiority of the ddI-containing regimen in this trial may be unrelated to ddI.

Buffered ddI powder is also available for liquid solution. The recommended dose is 250mg twice daily for patients over 60kg, and 167mg twice daily for those under 60kg.

The dose of ddI should be reduced in patients with liver or kidney damage.

Bristol-Myers Squibb stopped making ddI tablets in 2006 in the United States.

In 2000, the new enteric-coated (EC) capsule of ddI was approved for use in the European Union and the United States. The capsules are marketed as VidexEC.

The standard dose of the capsule formulation is the same as for ddI tablets. Patients over 60kg should take 400mg once a day or 200mg twice a day, while those weighing under 60kg should take 250mg once a day or 125mg twice a day.

In the two hours before and the two hours after taking the ddI capsules, patients should not eat or drink anything except water. Taking ddI capsules with food leads to lower levels of ddI in the blood, which may lead to the development of resistance.⁴ However, one study has found that the capsules may be taken with food in patients who have excellent adherence levels, without causing raised levels of treatment failure or discontinuation of treatment.⁵

The capsules’ coating protects the drug from being broken down by acid in the stomach, eliminating the need for an antacid buffer. The buffer is what makes ddI tablets bulky, and it can also cause diarrhoea and other gastrointestinal problems. The capsules also have fewer interactions with other drugs and do not need to be dissolved in water.