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Drug Interactions between amprenavir and Antabuse

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

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Interactions between your drugs

Major

disulfiram amprenavir

Applies to: Antabuse (disulfiram) and amprenavir

CONTRAINDICATED: Amprenavir oral solution contains a large amount of propylene glycol, which may produce a toxic reaction when coadministered with disulfiram or other drugs that may be capable of inhibiting aldehyde dehydrogenase (ALDH) such as metronidazole. Inhibition of ALDH results in accumulation of acetaldehyde during the metabolism of propylene glycol. High levels of acetaldehyde can produce an unpleasant physiologic response referred to as the 'disulfiram reaction'. Symptoms include flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, weakness, vertigo, blurred vision, and confusion. Severe reactions may result in respiratory depression, cardiovascular collapse, arrhythmia, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death. The interaction is well established for disulfiram. However, data for metronidazole and other nitroimidazoles are limited and conflicting.

MANAGEMENT: The use of amprenavir oral solution with disulfiram or metronidazole (oral, intravenous, and probably vaginal preparations) is considered contraindicated. Given their structural similarities to metronidazole, the same precaution may be applicable to other nitroimidazoles such as benznidazole and tinidazole, although clinical data are lacking.

References (4)
  1. (2001) "Product Information. Flagyl (metronidazole)." Searle
  2. (2022) "Product Information. MetroGel-Vaginal (metroNIDAZOLE topical)." Curatek Pharmaceuticals Ltd
  3. (2001) "Product Information. Agenerase (amprenavir)." Glaxo Wellcome
  4. (2004) "Product Information. Tindamax (tinidazole)." Presutti Laboratories Inc

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Drug and food interactions

Major

disulfiram food

Applies to: Antabuse (disulfiram)

CONTRAINDICATED: Consumption of ethanol during treatment with disulfiram may cause flushing, nausea, blurred vision, dyspnea, tachypnea, tachycardia, and hypotension. Death has been reported. The mechanism is probably related to inhibition of aldehyde dehydrogenase, the enzyme responsible for the oxidation of acetaldehyde to acetyl CoA. Accumulation of acetaldehyde probably results.

MANAGEMENT: Ethanol should be avoided in patients receiving disulfiram.

References (3)
  1. Jones RO (1949) "Death following the ingestion of alcohol in an antabuse treated patient." Can Med Assoc J, 60, p. 609-12
  2. Stoll D, King LE (1980) "Disulfiram-alcohol skin reaction to beer-containing shampoo." JAMA, 244, p. 2045
  3. van Ieperen L (1984) "Sudden death during disulfiram-ethanol reaction." S Afr Med J, 66, p. 165

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Moderate

amprenavir food

Applies to: amprenavir

GENERALLY AVOID: Administration with a high-fat meal may decrease the oral bioavailability of amprenavir. The mechanism is unknown. In healthy volunteers, consumption of a standardized high-fat meal decreased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of amprenavir (1200 mg single oral dose) by 36% and 21%, respectively, compared to administration in the fasted state. The time to reach Cmax (Tmax) was increased 44% following a high-fat meal.

Grapefruit juice does not appear to significantly affect the pharmacokinetics of amprenavir. In 12 healthy volunteers, administration with grapefruit juice (200 mL) decreased the mean peak plasma concentration (Cmax) of amprenavir (1200 mg single oral dose) by 22% compared to water. The median time to reach Cmax (Tmax) was prolonged from 0.75 to 1.13 hours. These pharmacokinetic changes are not thought to be clinically significant, since antiretroviral response is more closely associated with systemic exposure (AUC) and trough plasma concentration (Cmin), which were not affected in the study.

MANAGEMENT: Amprenavir may be taken with or without food, but should not be taken with a high-fat meal.

References (2)
  1. (2001) "Product Information. Agenerase (amprenavir)." Glaxo Wellcome
  2. Demarles D, Gillotin C, Bonaventure-Paci S, Vincent I, Fosse S, Taburet AM (2002) "Single-dose pharmacokinetics of amprenavir coadministered with grapefruit juice." Antimicrob Agents Chemother, 46, p. 1589-1590

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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.

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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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