[e-drug] EMEA warns against tenofovir-didanosine co-administration

["E-Drug" <e-drug@healthnet.org>]

E-DRUG: EMEA warns against tenofovir-didanosine co-administration
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[Another warning, this time from EMEA, with repercussions for ARV treatment in developing countries. Thanks to Richard for spotting. The full text and all annexes are available from EMEA at http://www.emea.eu.int/pdfs/human/press/pus/6233105en.pdf
WB]

EMEA PUBLIC STATEMENT

Efficacy and Safety concerns regarding the co-administration of
tenofovir disoproxil fumarate (TDF, Viread1) and didanosine (ddI, Videx2)

The European Medicines Agency (EMEA) and its Scientific Committee for human medicines (CHMP) have been made aware of new reports of virological failure and emergence of resistance following co-administration of tenofovir disoproxil fumarate and didanosine. These have been observed in several clinical studies3-5 in which tenofovir disoproxil fumarate and didanosine were coadministered with a non-nucleoside reverse transcriptase inhibitor in HIV-infected treatment-naive adult patients with high baseline viral load and low CD4 cell counts.

Similar reports have been previously observed with this dual combination in the context of triple combination therapy with a nucleoside/nucleotide reverse transcriptase inhibitor and were the subject of recommendations by the EMEA on 22 October 2003 (http://www.emea.eu.int/pdfs/human/press/pus/509403en.pdf). The precise nature of any interaction leading to non-response is still not known. The CHMP cannot exclude that the same findings can be observed in other contexts, as in antiretroviral experienced patients and/or in combination with protease inhibitors.

This co-administration was already considered as a safety concern due to the systemic over-exposure (40-60%) of didanosine resulting from a pharmacokinetic interaction with tenofovir. Such an overexposure
may increase the risk for didanosine-related adverse events (e.g. pancreatitis, lactic acidosis).

Based on the new clinical data the EMEA wishes to point out the following information:

 The co-administration of tenofovir disoproxil fumarate and didanosine is not recommended within any antiretroviral combination therapy, and particularly in patients with high viral load and low CD4 cell count.

 Rare, sometimes fatal, cases of pancreatitis and lactic acidosis have been reported with the coadminstration of tenofovir and didanosine.

 If this combination is considered to be strictly necessary, patients should be closely monitored for efficacy and didanosine-related adverse events.

The Product Information for Viread has now been modified to reflect the above-mentioned information and is appended (Annex 2) to this Public Statement.
See Annex 1 for Reference List

Media enquiries only please contact:
Martin Harvey Allchurch
Tel. (44-20) 74 18 84 27
E-mail: press@emea.eu.int

[Annexes are in the original PDF; see www.emea.eu.int/pdfs/human/press/pus/6233105en.pdf]