Drug interactions

Many other medications can reduce the amount of ddI (didanosine, Videx / VidexEC) that the body absorbs . ddI tablets contain an antacid to prevent the drug being destroyed by stomach acid. Drugs that require an acidic stomach for proper absorption should be taken at least two hours before ddI tablets. These include:

  • Ciprofloxacin (Ciproxin).
  • Dapsone.
  • Itraconazole (Sporanox).
  • Ketoconazole (Nizoral)
  • Levofloxacin (Tavanic).
  • Moxifloxacin (Avelox).
  • Naldixic acid (Uriben).
  • Norfloxacin (Utinor).
  • Orfloxacin (Tarivid).

ddI capsules may be taken at the same time as these drugs.

ddI tablets should not be taken at the same time of the day as any protease inhibitors as they may prevent the protease inhibitors from being properly absorbed. Patients taking ddI and a protease inhibitor should take the protease inhibitor at least two hours before the ddI tablets. Indinavir (Crixivan) may be particularly difficult to schedule, since both drugs have to be taken on an empty stomach. Even if indinavir is being taken with ritonavir (Norvir), thus avoiding food restrictions, it must not be taken within two hours of ddI tablets.

There is no need for the two-hour gap between indinavir (Crixivan) and ddI capsules, although protease inhibitors which must be taken with food should not be dosed at the same time as ddI capsules.

If ddI is taken with tenofovir (Viread), levels of ddI can increase by up to 64%.1 2 This can put patients at a high risk of side-effects such as pancreatitis and neuropathy. However, this combination of drugs can also cause dramatic falls in CD4 cell counts in up to 80% of patients, even when they have undetectable viral loads.3 4 This is thought to be due to the very high levels of ddI leading to death of the white blood cells.5 These paradoxical falls in CD4 cell count are more likely in patients who have been taking ddI for longer, with higher doses of ddI relative to weight and in patients with kidney damage.6 Furthermore, this combination of NRTIs has been linked to virological failure and the development of resistance in numerous studies.7 8

A dose reduction from 400 to 250mg ddI once a day may be considered for patients who need to take these two drugs together to construct a viable anti-HIV regimen, and close monitoring for side-effects and CD4 cell count declines is advised.9 10 This was reflected in ‘Dear Doctor’ letters from Bristol-Myers Squibb and Gilead, tenofovir’s manufacturer, in November 2004 and March 2005, and a warning from the European Medicines Agency (EMEA) in April 2005.

Certain drugs can increase the risk of ddI-related pancreatitis and should be avoided by patients taking ddI. These include the following:

  • d4T (stavudine, Zerit).
  • Demeclocycline hydrochloride (Ledermycin).
  • Doxycycline (Vibramycin / Vibramycin-D).
  • Hydroxycarbamide (Hydrea).
  • Lymecycline (Tetralysal 300).
  • Minocycline (Minocin MR / Sebomin MR).
  • Oxytetracycline.
  • Pentamidine isetionate (Pentacarinat).
  • Tetracycline.

Alcohol should also be avoided by people taking ddI because it can increase the risk of pancreatitis. Similarly, rifampicin (Rifadin / Rimactane), rifabutin (Mycobutin), ganciclovir (Cymevene), interferon alfa (IntronA / Roferon-A / Viraferon), ribavirin (Copegus / Rebetol / Virazole), co-trimoxazole (Septrin) and some stomach ulcer drugs including H2-receptor blockers and omeprazole (Losec) may increase the risk of pancreatitis.11 12 13

Methadone hydrochloride (Methadose) may seriously reduce absorption of ddI, particularly the tablet form. Studies are underway to investigate whether the capsule form of ddI is better absorbed in people taking methadone.

References

  1. Flaherty J et al. Coadministration of tenofovir DF (TDF) and didanosine (ddI): a pharmacokinetic (PK) and safety evaluation. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, abstract I-1729, 2001
  2. Kearney BP et al. Tenofovir DF and didanosine EC (ddI EC): investigation of pharmacokinetic (PK) drug-drug and drug-food interactions. 14th International AIDS Conference, Barcelona, abstract PeB9026, 2002
  3. 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
  4. 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
  5. Kakuda TN et al. CD4 cell decline with didanosine and tenofovir and failure of triple nucleoside / nucleotide regimens may be related. AIDS 18: 2442-2444, 2004
  6. Lacombe K et al. Risk factors for CD4 lymphopenia in patients treated with a tenofovir/didanosine high dose-containing highly active antiretroviral therapy regimen. AIDS 19: 1107-1109, 2005
  7. Podzamczer D et al. Early virologic failure with a combination of tenofovir, didanosine and efavirenz. Antivir Ther 10: 171-177, 2005
  8. 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
  9. Kearney BP et al. Didanosine and tenofovir DF drug-drug interaction: assessment of didanosine dose reduction. Tenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 533, 2003
  10. Karrer U et al. Dose-dependent influence of didanosine on immune recovery in HIV-infected patients treated with tenofovir. AIDS 19: 1987-1994, 2005
  11. Fleischer R et al. Evidence suggesting mitochondrial toxicity in HIV / HCV co-infected patients receiving ribavirin and didanosine. Tenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract P763, 2003
  12. Jost R et al. Fatal drug-induced pancreatitis in HIV. Lancet 341: 1412, 1993
  13. Hor T et al. Concomitant ddI / d4T and IFN (standard or pegylated) / ribavirin treatments may induce a high risk of mitochondrial toxicity in HIV / HCV infected patients (ANRS HCO-2 RIBAVIC study). 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, abstract H-1735, 2002
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.