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Drug Interactions between Co-trimoxazole and ganciclovir

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

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Interactions between your drugs

Minor

ganciclovir trimethoprim

Applies to: ganciclovir and Co-trimoxazole (sulfamethoxazole / trimethoprim)

The coadministration of ganciclovir or its prodrug, valganciclovir, with trimethoprim may result in elevated plasma concentrations of ganciclovir. In 12 subjects with HIV and CMV coinfection, trimethoprim (200 mg orally once a day) increased the half-life of ganciclovir (1000 mg orally every 8 hours) by an average of 15% and decreased its renal clearance by 16%. The mechanism is unknown but may involve the competitive inhibition of ganciclovir renal tubular secretion by trimethoprim. Ganciclovir had minimal effect on the pharmacokinetics of trimethoprim. This interaction is unlikely to be of clinical significance. . However, the use of ganciclovir with other potentially myelotoxic drugs such as trimethoprim may increase the risk and severity of these adverse events due to additive pharmacodynamic effects. The potential for this effect should be kept in consideration and the patient monitored for hematologic adverse effects.

References (4)
  1. (2002) "Product Information. Cytovene (ganciclovir)." Genentech
  2. (2001) "Product Information. Valcyte (valganciclovir)." Roche Laboratories
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. 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
Moderate

sulfamethoxazole food

Applies to: Co-trimoxazole (sulfamethoxazole / trimethoprim)

MONITOR: Two cases have been reported in which patients on sulfamethoxazole-trimethoprim therapy, after consuming beer, reported flushing, heart palpitations, dyspnea, headache, and nausea (disulfiram - alcohol type reactions). First-generation sulfonylureas have been reported to cause facial flushing when administered with alcohol by inhibiting acetaldehyde dehydrogenase and subsequently causing acetaldehyde accumulation. Since sulfamethoxazole is chemically related to first-generation sulfonylureas, a disulfiram-like reaction with products containing sulfamethoxazole is theoretically possible. However, pharmacokinetic/pharmacodynamic data are lacking and in addition, the two reported cases cannot be clearly attributed to the concomitant use of sulfamethoxazole-trimethoprim and alcohol.

MANAGEMENT: Patients should be alerted to the potential for this interaction and although the risk for this interaction is minimal, caution is recommended while taking sulfamethoxazole-trimethoprim concomitantly with alcohol.

References (2)
  1. Heelon MW, White M (1998) "Disulfiram-cotrimoxazole reaction." Pharmacotherapy, 18, p. 869-70
  2. Mergenhagen KA, Wattengel BA, Skelly MK, Clark CM, Russo TA (2020) "Fact versus fiction: a review of the evidence behind alcohol and antibiotic interactions." Antimicrob Agents Chemother, 64, e02167-19

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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