Tenofovir (Viread) and ddI (Videx) should not be used together, European medicine regulatory authorities have warned in a public statement. The caution follows a "Dear Doctor" letter issued by Gilead Sciences and Bristol Myers Squibb (BMS), the manufacturers of the drugs last month.
In a separate move, BMS has issued a "Dear Doctor" letter in the US informing healthcare providers that the warning regarding the use of efavirenz (Sustiva) during pregnancy has been strengthened from "risk of foetal harm cannot be ruled out" to "positive evidence of foetal risk."
Co-administration of tenofovir/ddI
The European Medicines Agency (EMEA) and its Scientific Committee for Human Medicines (CHMP) issued a caution regarding the co-administration of tenofovir/ddI after several studies found virological failure and resistance in individuals taking the two drugs as part of a HAART regimen. These studies involved treatment-naïve individuals taking a non-nucleoside analogue who had high viral loads and low CD4 cell counts.
As the earlier "Dear Doctor" letter from the pharmaceutical companies highlighted, the EMEA and CHMP are warning that failure of a regimen including tenofovir/ddI cannot be excluded in other contexts, such as treatment experienced individuals, and/or the use of the two drugs with a protease inhibitor.
The EMEA and CHMP highlight the following information:
- The use of tenofovir/ddI is not recommended in any antiretroviral combination, and particularly in individuals with high viral loads and low CD4 cell counts.
- Rare, but sometimes fatal, cases of pancreatitis and lactic acidosis have been reported in individuals taking tenofovir/ddI.
- If a combination of tenofovir/ddI is considered strictly necessary, patients should be monitored very closely to ensure that the regimen is working and they are not developing side-effects.
Efavirenz
BMS has issued a "Dear Doctor" letter in the US strengthening the warning about the risk of foetal abnormalities if efavirenz is used during pregnancy. The caution regarding the use of efavirenz during pregnancy has been strengthened after four retrospective reports of neural tube defects in infants born to women who took efavirenz during the first trimester of pregnancy. Three cases of meningomyeicele and one case of Dandy Walker Syndrome were reported.
BMS advise that women capable of becoming pregnant should have a pregnancy test before starting treatment with efavirenz. If efavirenz is used during the first three months of pregnancy, or if a women becomes pregnant whilst taking efavirenz, they should be counselled about the possible risks of foetal abnormality. Women taking efavirenz should use barrier contraception in combination with other contraceptive methods.
Foetal abnormalities were found during efavirenz laboratory studies involving monkeys. There are, however, limited data on birth defects in women taking efavirenz during pregnancy. The outcomes of pregnancy have been prospectively reviewed for 206 women taking efavirenz. Birth defects occurred in five of the 188 infants exposed to efavirenz during the first trimester. None of these prospectively reported defects were neural tube defects. None of the 13 live births with second or third trimester exposure to efavirenz involved infants with defects.
However, in light of the four retrospective reports, all involving neural tube defects, and all involving use of efavirenz during the first trimester, BMS enhanced the warning about use of the drug during pregnancy. This warning will be included in the efavirenz product information contained in each dispensed pack of the drug.