Drug interactions

Zidovudine (AZT, Retrovir) should not be taken with stavudine (d4T, Zerit), as these two drugs reduce each other’s anti-HIV effects. A similar interaction occurs between zidovudine and ribavirin (Copegus / Rebetol / Virazole), which is used to treat hepatitis C.

Zidovudine is removed from the body by the kidneys after chemical modification or ‘glucuronidation’ in the liver. Other medicines that are removed in the same way may interact with zidovudine and may require dose adjustments. For example, co-administration of zidovudine with the tuberculosis drug rifampicin (Rifadin / Rimactane) can lead to elevations in rifampicin levels, although it is not known whether this is clinically significant. Similarly, the drug probenecid (Benuryl / Probecid), which is used to prevent kidney toxicity due to cidofovir (Vistide) treatment for cytomegalovirus infection, reduces the metabolism of zidovudine. This leads to elevated levels of zidovudine and increased risk or severity of side-effects.

Patients taking the anti-convulsant drug phenytoin (Epanutin) with zidovudine should be closely monitored, as co-administration of the drugs can cause increases or decreases in phenytoin levels. Studies have shown that atovaquone (Wellvone) and valproic acid (Depakote) also increase exposure to zidovudine.

The risk of low white blood cell counts (neutropenia) is increased in patients taking ganciclovir (Cymevene), doxorubicin (Caelyx / Myocet), trimetrexate or cotrimoxazole (Septrin) at the same time as zidovudine. The risk of anaemia is increased in patients taking pyrimethamine plus sulphadiazine (Fansidar), used for treating toxoplasmosis.

Methadone (Methadose) increases levels of zidovudine by about twofold, so people taking both drugs need only take half the standard dose of zidovudine to get the same anti-HIV effect.

Other drugs that should be co-administered with zidovudine with caution include:

• Aspirin.
• Cimetidine (Dyspamet / Tagamet).
• Clofibrate.
• Codeine.
• Dapsone.
• Indometacin (Rimacid).
• Isoprinosine.
• Ketoprofen (Orudis / Orovail).
• Lorazepam.
• Morphine.
• Naproxen (Naprosyn / Synflex).
• Oxazepam.

Similarly, the risk of zidovudine-related side-effects may be increased with the following drugs:

• Amphotericin (Fungilin / Fungizone).
• Flucytosine.
• Interferon alfa (Intron-A / Roferon-A / Viraferon).
• Ribavirin (Copegus / Rebetol / Virazole).
• Systemic pentamidine (Pentacarinat).
• Vinblastine (Velbe).
• Vincristine (Oncovin).

Patients taking these drugs alongside zidovudine should be closely monitored for kidney and blood problems.