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Drug Interactions between abacavir / lamivudine / zidovudine and ganciclovir

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

zidovudine ganciclovir

Applies to: abacavir / lamivudine / zidovudine and ganciclovir

GENERALLY AVOID: Limited data concerning the coadministration of ganciclovir and zidovudine do not suggest the potential for a clinically significant pharmacokinetic interaction. However, the possibility of increased risk and severity of hematologic toxicity, especially neutropenia and anemia, due to additive myelosuppressive effects should be considered during concomitant therapy. The majority of patients may be unable to tolerate full dosages of these drugs in combination.

MANAGEMENT: It is best to avoid the use of zidovudine with ganciclovir or its prodrug, valganciclovir, whenever possible. If simultaneous therapy is deemed necessary, reduced dosages of one (usually zidovudine) or both drugs may be required. Close clinical and laboratory monitoring for the development of severe hematologic adverse effects is recommended. Alternatively, a less myelotoxic agent such as foscarnet may be considered in lieu of ganciclovir to treat cytomegalovirus infections in immunocompromised patients receiving zidovudine.

References (8)
  1. Hochster H, Dieterich D, Bozzette S, et al. (1990) "Toxicity of combined ganciclovir and zidovudine for cytomegalovirus disease associated with AIDS." Ann Intern Med, 113, p. 111-7
  2. Burger DM, Meenhorst PL, Koks CH, Beijnen JH (1993) "Drug interactions with zidovudine." AIDS, 7, p. 445-60
  3. Taburet AM, Singlas E (1996) "Drug interactions with antiviral drugs." Clin Pharmacokinet, 30, p. 385-401
  4. (2001) "Product Information. Valcyte (valganciclovir)." Roche Laboratories
  5. Cimoch PJ, Lavelle J, Pollard R, et al. (1998) "Pharmacokinetics of oral ganciclovir alone and in combination with zidovudine, didanosine, and probenecid in HIV-infected subjects." J Acquire Immune Defic Hum Retrovirol, 17, p. 227-34
  6. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  7. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  8. Cerner Multum, Inc. "Australian Product Information."

Drug and food interactions

Moderate

ganciclovir food

Applies to: ganciclovir

ADJUST DOSING INTERVAL: Food delays but enhances the oral absorption and bioavailability of ganciclovir capsules, possibly due to prolongation of gastrointestinal transit time. In 20 HIV- and CMV-seropositive subjects, ganciclovir dosing (1000 mg every 8 hours) following a standardized high-fat breakfast increased the mean steady-state peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of ganciclovir by an average of 15% and 22%, respectively, compared to dosing after an overnight fast. The time to reach peak plasma concentration (Tmax) was prolonged from 1.8 to 3 hours. In another study of 15 such patients, administration of ganciclovir (2000 mg) within 30 minutes following a high-fat breakfast increased the Cmax and AUC an average of 111% and 114%, respectively, compared to administration in the fasting state (i.e. at least 1 hour before or 2 hours after a meal or snack). Over the total day of dosing (2000 mg orally three times a day), there was a mean increase of 48% and 97% in Cmax and AUC, respectively, and a 36% decrease in half-life during administration with meals.

MANAGEMENT: To ensure maximal oral absorption, oral ganciclovir should be administered with or immediately after a meal.

References (3)
  1. (2002) "Product Information. Cytovene (ganciclovir)." Genentech
  2. Lavelle J, Follansbee S, Trapnell CB, Buhles WC, Griffy KG, Jung D, Dorr A, Conner J (1996) "Effect of food on the relative bioavailability of oral ganciclovir." J Clin Pharmacol, 36, p. 238-41
  3. Jung D, Griffy K, Dorr A (1999) "Effect of food on high-dose oral ganciclovir disposition in HIV-positive subjects." J Clin Pharmacol, 39, p. 161-5
Minor

zidovudine food

Applies to: abacavir / lamivudine / zidovudine

Food may have variable effects on the oral bioavailability of zidovudine. Fatty foods have been reported to decrease the rate and extent of zidovudine absorption following oral administration. In a study of 13 AIDS patients, mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of zidovudine were 2.8 and 1.4 times higher, respectively, in fasting patients than in those administered the medication with breakfast. In addition, variations in plasma zidovudine concentrations were increased when administered in the fed state. In another study of eight patients, the time to reach peak concentration (Tmax) was increased from 0.68 to 1.95 hours, and Cmax was reduced by 50% when zidovudine was administered with a liquid high-fat meal relative to fasting. Protein meals can also delay the absorption and reduce the Cmax of zidovudine, although the extent of absorption is not significantly affected. The clinical significance of these alterations, if any, is unknown. The product labeling states that zidovudine may be taken with or without food.

References (4)
  1. Lotterer E, Ruhnke M, Trautman M, et al. (1991) "Decreased and variable systemic availability of zidovudine in patients with AIDS if administered with a meal." Eur J Clin Pharmacol, 40, p. 305-8
  2. Unadkat JD, Collier AC, Crosby SS, et al. (1990) "Pharmacokinetics of oral zidovudine (azidothymidine) in patients with AIDS when administered with and without a high-fat meal." AIDS, 4, p. 229-32
  3. (2001) "Product Information. Retrovir (zidovudine)." Glaxo Wellcome
  4. Sahai J, Gallicano K, Garber G, et al. (1992) "The effect of a protein meal on zidovudine pharmacokinetics in HIV-infected patients." Br J Clin Pharmacol, 33, p. 657-60

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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