Taking enteric coated (EC) ddI (Videx EC) and tenofovir (Viread)with food leads to a 60% increase in blood levels of ddI, according to data released last week.
Bristol-Myers Squibb (BMS) has written to doctors in the US alerting them to a study conducted by Gilead Sciences to investigate the pharmacokinetics of ddI when it was given at the same time as tenofovir. The study looked at two dosing approaches. Either EC ddI was given without food two hours before dosing with tenofovir with food; or both drugs were given together with food. Tenofovir absorption is improved when the drug is taken with food, but ddI should be taken on an empty stomach.
The results of the study showed that when EC ddI was given two hours before tenofovir with a light meal, the amount of ddI in the blood increased by 46% compared to when ddI was administered on its own without food. When ddI was taken in tablet form one hour before tenofovir (both on an empty stomach) ddI levels were increased by an average of 28% (range 11% to 48%), suggesting that even where lower tenofovir.
When EC ddI and tenofovir were given together with a light meal, there was a 60% increase in the amount of ddI compared to ddI dosing on its own in a fasted state. BMS ran into trouble in September 2000 before the launch of EC ddI, when it became clear that taking the drug with food caused a 27% reduction in blood levels when compared with dosing on an empty stomach.
BMS said that “it is evaluating the issue further” and in its letter to doctors recommended the close monitoring of people taking both EC ddI and tenofovir for ddI-related side effects, particularly pancreatitis, peripheral neuropathy and liver toxicities, all of which occur more frequently when ddI is given in combination with d4T (stavudine, Zerit).
Dr Andrew Clark, UK medical adviser for BMS Virology, told aidsmap that “although the Cmax of Videx EC is blunted considerably compared with Videx tablets, thus reducing the risk of pancreatitis, combining it with tenofovir could take it up above the levels seen with the buffered formulation, and so increase the risk of pancreatitis”.
In the absence of data on dose reduction of Videx and Videx EC, BMS is unable to offer further guidance at this time for regulatory reasons, so NAM asked UK doctors and pharmacists if they would advise patients that it was safe to take EC ddI and tenofovir at the same time, with a meal. Differing practice was evident at a number of large treatment centres in London.
Dr Mike Youle of the Royal Free Hospital, London, said that he already advised patients that it was possible to dose ddI and tenofovir with food, and would monitor closely for toxicities
Dr Graeme Moyle of the Kobler Centre at the Chelsea and Westminster Hospital in London said that he would give patients the option of reducing the dose of EC ddI to 250mg a day, or maintaining the existing 400mg dose and monitoring for side effects. An alternative strategy would be to take the ddI in a fasted state before breakfast and the tenofovir with an evening meal.
However, Rosy Weston, HIV Pharmacist at St Mary’s Hospital in London, said “we have been concerned about this interaction for some time and have
been advising patients to keep their ddI and tenofovir doses separate. The majority of our patients take their ddI at night and tenofovir in the morning with food.”
Dr Ian Williams of the Mortimer Market Centre at University College Hospital, London, said “those patients who are unable to take ddI on an empty stomach and tenofovir at least one hour later with food because of valid reasons can be reassured that on these data, taking the two together with food would not affect efficacy. I would be more concerned to emphasise the need to monitor more closely for ddI toxicity, particularly those at higher risk, and ensure those with low weights are on the correct dose of ddI.”
He added that data on ddI dose reduction when coadministered with tenofovir are needed. These are likely to be available by the time of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) which takes place at the end of September, say BMS.