Do amitriptyline, levothyroxine, methenamine hippurate, estriol (estrogen) cream, pivmecillinam, propranolol, or fluconazole cause a disulfiram‑like reaction?

Disulfiram-Like Reactions with Listed Medications

Among the medications listed, only fluconazole has documented potential to cause a disulfiram-like reaction when combined with alcohol, though this risk is primarily related to its class (imidazole antifungals) rather than fluconazole specifically.

Fluconazole and Imidazole Antifungals

• Fluconazole belongs to the imidazole antifungal class, and imidazole derivatives as a group have been implicated in disulfiram-like reactions 1
• The mechanism involves inhibition of aldehyde dehydrogenase, leading to acetaldehyde accumulation when alcohol is consumed, resulting in flushing, nausea, tachycardia, headache, and potentially hypotension 1, 2
• While metronidazole (another imidazole) is well-documented to cause this reaction, caution has been advised with use of all imidazoles including fluconazole 1
• Ketoconazole, another imidazole antifungal, is specifically noted for cardiotoxic risks through cytochrome P450 interactions, though the disulfiram-like reaction mechanism differs 3

Medications WITHOUT Disulfiram-Like Reaction Risk

Amitriptyline:

• No disulfiram-like reaction documented 3
• Primary concerns are QT prolongation and drug interactions via cytochrome P450 metabolism 3
• Can cause weight gain and worsen obstructive sleep apnea 3

Levothyroxine:

• No disulfiram-like reaction documented
• No relevant interactions with alcohol metabolism identified in the evidence

Methenamine hippurate:

• No disulfiram-like reaction documented
• No relevant interactions with alcohol metabolism identified in the evidence

Estriol (estrogen) cream:

• No disulfiram-like reaction documented
• Topical estrogen preparations have minimal systemic effects relevant to alcohol metabolism

Pivmecillinam:

• No disulfiram-like reaction documented
• This is a penicillin derivative, not a cephalosporin (cephalosporins like cefoperazone and cefmetazole can cause disulfiram-like reactions) 4

Propranolol:

• Interestingly, propranolol has been studied for its ability to inhibit acetaldehyde oxidation and increase blood acetaldehyde levels, potentially producing a deterrent effect on alcohol consumption 5
• However, this is an experimental finding and propranolol is not clinically recognized as causing disulfiram-like reactions in standard practice 5
• Primary concerns with propranolol are cardiovascular effects and potential to worsen obstructive sleep apnea 3

Clinical Recommendations

• Advise patients taking fluconazole to avoid alcohol consumption during treatment and for several days after completion 1
• If a patient on fluconazole develops flushing, tachycardia, nausea, headache, or hypotension after alcohol intake, manage supportively with volume resuscitation; severe hypotension may require noradrenaline rather than dopamine 6
• The other medications listed (amitriptyline, levothyroxine, methenamine hippurate, estriol cream, pivmecillinam, propranolol) do not require specific alcohol avoidance counseling related to disulfiram-like reactions 3