Drug interactions

Tenofovir (Viread) has an important interaction with the nucleoside reverse transcriptase inhibitor ddI (didanosine, Videx / VidexEC), in three ways:

  • Combining the drugs results in increased exposure to ddI.1 This can lead to a greater risk of ddI-related side-effects such as lactic acidosis, pancreatitis and peripheral neuropathy, which have been fatal in some cases.2 3 4 5 Research suggests that reducing the once-daily dose of ddI from 400 to 250mg should result in acceptable exposure to ddI when taken with the standard dose of tenofovir daily, although there have been reports of lactic acidosis even with this reduced dose of ddI.5 6
  • The combination of ddI and tenofovir has also been linked to falls in CD4 cell counts in treatment-experienced patients who switch to the drugs as well as patients who are taking tenofovir as part of their first treatment regimen.7 8 However, this may be prevented by using a lower dose of 250mg ddI in patients taking tenofovir.9
  • The combination of ddI and tenofovir with nevirapine (Viramune) or efavirenz (Sustiva) may also be problematic due to a higher risk of virologic failure.10 11 12

Gilead and ddI’s manufacturer Bristol-Myers Squibb issued ‘Dear Doctor’ letters in November 2004 and March 2005 warning healthcare providers not to prescribe tenofovir and ddI together unless absolutely necessary, because of the risks of side-effects and treatment failure.

When a patient is taking tenofovir as well as other medicines that are known to cause kidney toxicity, there may be an increased risk of kidney side-effects. If co-administration with drugs such as ganciclovir (Cymevene), foscarnet (Foscavir), pentamidine (Pentacarinat), amphotericin (Fungilin / Fungizone), vancomycin (Vancocin), interleukin-2, cidofovir (Vistide) or the aminoglycosides cannot be avoided, weekly monitoring of kidney function is recommended. ddI can also increase the risk of kidney toxicity, possibly through damaging the mitochondria in the kidney.13

Tenofovir levels are also slightly increased when dosed with ritonavir-boosted lopinavir (Kaletra) or atazanavir (Reyataz). Although some studies have reported no negative effects of tenofovir on lopinavir concentrations in treatment-experienced patients, significant reductions in lopinavir and ritonavir minimum concentrations have been seen.14 15 Tenofovir also decreases atazanavir levels.16 When the two drugs are taken together, it is recommended that atazanavir be boosted with ritonavir (Norvir).

References

  1. Kearney B et al. A multiple-dose, randomized, crossover, drug interaction study between tenofovir DF and lamivudine or didanosine. First International AIDS Society Conference on HIV Pathogenesis and Treatment, Buenos Aires, abstract 337, 2001
  2. Guo Y et al. Fatal lactic acidosis associated with coadministration of didanosine and tenofovir disoproxil fumarate. Pharmacotherapy 24: 1089-1094, 2004
  3. Martinez E et al. Pancreatic toxic effects associated with coadministration of didanosine and tenofovir in HIV-infected adults. Lancet 364: 65-67, 2004
  4. Moyle G et al. Unexpected drug interactions and adverse events with antiretroviral drugs. Lancet 364: 8-10, 2004
  5. Kirian MA et al. Acute onset of pancreatitis with concomitant use of tenofovir and didanosine. Ann Pharmacother 38: 1660-1663, 2004
  6. Masia M et al. Didanosine-associated toxicity. A predictable complication of therapy with tenofovir and didanosine? J Acquir Immune Defic Syndr 35: 427-428, 2005
  7. Negredo E et al. Unexpected CD4 cell count decline in patients receiving didanosine and tenofovir-based regimens despite undetectable viral load. AIDS 18: 459-463, 2004
  8. Barrios A et al. Paradoxical CD4+ T-cell decline in HIV-infected patients with complete virus suppression taking tenofovir and didanosine. AIDS 19: 569-576, 2005
  9. Karrer U et al. Dose-dependent influence of didanosine on immune recovery in HIV-infected patients treated with tenofovir. AIDS 19: 1987-1994, 2005
  10. Maitland D et al. Early virologic failure in HIV-1 infected subjects on didanosine / tenofovir / efavirenz: 12-week results from a randomized trial. AIDS 19: 1183-1188, 2005
  11. Podzamczer D et al. Early virologic failure with a combination of tenofovir, didanosine and efavirenz. Antivir Ther 10: 171-177, 2005
  12. Leon A et al. Early virological failure in treatment-naïve HIV-infected adults receiving didanosine and tenofovir plus efavirenz or nevirapine. AIDS 19: 213-215, 2005
  13. Cote HC et al. Exploring mitochondrial nephrotoxicity as a potential mechanism of kidney dysfunction among HIV-infected patients on highly active antiretroviral therapy. Antivir Ther 11: 79-86, 2006
  14. Amantea MA et al. Pharmacokinetic drug-drug interaction between capravirine, lopinavir/ritonavir and tenofovir in healthy volunteers. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, abstract A-1609, 2003
  15. Breilh D et al. Pharmacokinetic drug interaction of lopinavir / ritonavir in combination with tenofovir in experienced HIV+ patients. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, abstract A-445, 2004
  16. Taburet AM et al. Interactions between atazanavir-ritonavir and tenofovir in heavily pretreated human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 48: 2091-2096, 2004
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap
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This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.