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Drug Interactions between abacavir / lamivudine / zidovudine and Uroplus

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

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Interactions between your drugs

Minor

zidovudine sulfamethoxazole

Applies to: abacavir / lamivudine / zidovudine and Uroplus (sulfamethoxazole / trimethoprim)

Limited data indicate that zidovudine may significantly increase the serum half-life of both trimethoprim (TMP) and sulfamethoxazole (SMX). The mechanism is not known, but may be related to an increase in the volume of distribution of each drug. In addition, trimethoprim can decrease the renal clearance of zidovudine and its glucuronide metabolite by inhibiting their tubular secretion. However, net clearance is not affected because zidovudine is mostly metabolized and the glucuronide may be eliminated via biliary excretion. This interaction is not likely to be clinically important except when hepatic glucuronidation is also impaired by liver disease or drug inhibition.
Recommended management consists of monitoring for side effects of each drug and reducing dosages as necessary.

References

  1. Chatton JY, Munafo A, Chave JP, et al. "Trimethoprim, alone or in combination with sulphamethoxazole, decreases the renal excretion of zidovudine and its glucuronide." Br J Clin Pharmacol 34 (1992): 551-4
  2. Canas E, Pachon J, Garciapesquera F, Castillo JR, Viciana P, Cisneros JM, Jimenezmejias ME "Absence of effect of trimethoprim-sulfamethoxazole on pharmacokinetics of zidovudine in patients infected with human immunodeficiency virus." Antimicrob Agents Chemother 40 (1996): 230-3
  3. Lee BL, Safrin S, Makrides V, Gambertoglio JG "Zidovudine, trimethoprim, and dapsone pharmacokinetic interactions in patients with human immunodeficiency virus infection." Antimicrob Agents Chemother 40 (1996): 1231-6

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Minor

zidovudine trimethoprim

Applies to: abacavir / lamivudine / zidovudine and Uroplus (sulfamethoxazole / trimethoprim)

Limited data indicate that zidovudine may significantly increase the serum half-life of both trimethoprim (TMP) and sulfamethoxazole (SMX). The mechanism is not known, but may be related to an increase in the volume of distribution of each drug. In addition, trimethoprim can decrease the renal clearance of zidovudine and its glucuronide metabolite by inhibiting their tubular secretion. However, net clearance is not affected because zidovudine is mostly metabolized and the glucuronide may be eliminated via biliary excretion. This interaction is not likely to be clinically important except when hepatic glucuronidation is also impaired by liver disease or drug inhibition.
Recommended management consists of monitoring for side effects of each drug and reducing dosages as necessary.

References

  1. Chatton JY, Munafo A, Chave JP, et al. "Trimethoprim, alone or in combination with sulphamethoxazole, decreases the renal excretion of zidovudine and its glucuronide." Br J Clin Pharmacol 34 (1992): 551-4
  2. Canas E, Pachon J, Garciapesquera F, Castillo JR, Viciana P, Cisneros JM, Jimenezmejias ME "Absence of effect of trimethoprim-sulfamethoxazole on pharmacokinetics of zidovudine in patients infected with human immunodeficiency virus." Antimicrob Agents Chemother 40 (1996): 230-3
  3. Lee BL, Safrin S, Makrides V, Gambertoglio JG "Zidovudine, trimethoprim, and dapsone pharmacokinetic interactions in patients with human immunodeficiency virus infection." Antimicrob Agents Chemother 40 (1996): 1231-6

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Minor

trimethoprim lamiVUDine

Applies to: Uroplus (sulfamethoxazole / trimethoprim) and abacavir / lamivudine / zidovudine

In a study with 14 HIV-positive patients, coadministration of trimethoprim/sulfamethoxazole (trimethoprim/sulfamethoxazole DS once a day for 5 days) and lamivudine (300 mg single dose on day 5) resulted in a mean decrease of 35% in lamivudine renal clearance and a mean increase of 43% in lamivudine area under the plasma concentration-time curve. The mechanism of interaction is thought to be competitive inhibition of tubular secretion by trimethoprim. Lamivudine did not affect the pharmacokinetic profile of trimethoprim/sulfamethoxazole. Given the favorable safety profile of lamivudine, this interaction is unlikely to be of clinical significance. However, patients with renal dysfunction should be monitored carefully and the lamivudine dose adjusted if necessary. In addition, it should be noted that the effect of higher dosages of trimethoprim/sulfamethoxazole on lamivudine pharmacokinetics has not been investigated.

References

  1. "Product Information. Epivir (lamivudine)." Glaxo Wellcome PROD (2001):
  2. Moore KHP, Yuen GJ, Raasch RH, Eron JJ, Martin D, Mydlow PK, Hussey EK "Pharmacokinetics of lamivudine administered alone and with trimethoprim-sulfamethoxazole." Clin Pharmacol Ther 59 (1996): 550-8
  3. Cerner Multum, Inc. "Australian Product Information." O 0

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Drug and food interactions

Moderate

sulfamethoxazole food

Applies to: Uroplus (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

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

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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

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

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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.

See also

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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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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