Infectious Disease Compendium

Metronidazole (Flagyl®)

Dosing

CrCl Formula

CrCl > 80: 125- 500 mg po/iv q 6 to 12 (usually q 12).

CrCl 80-50: 125- 500 mg po/iv q 6 to 12 (usually q 12).

CrCl 50-10: 125- 500 mg po/iv q 6 to 12 (usually q 12).

CrCl < 10: 125- 500 mg po/iv q 6 to 12 (usually q 12).

Hemodialysis: 125- 500 mg po/iv q 6 to 12 (usually q 12).

Peritoneal dialysis: 125- 500 mg po/iv q 6 to 12 (usually q 12).

Important side effects

Ataxia, dizziness, headache, peripheral neuropathy (higher incidence of peripheral neuropathy in patients receiving >42 total grams (>4 weeks (PubMed)) of metronidazole), seizures, anorexia, gi discomfort, metallic taste, n/v, disulfiram-like (antabuse) reaction with puke central.

"The syndrome frequently involves cerebellar dysfunction and more rarely involves seizures or EEG abnormalities. The metronidazole toxicity results in "characteristic reversible MRI signal abnormalities in the cerebellar dentate nuclei, dorsal brainstem, or splenium of the corpus callosum (PubMed).

Important drug interactions

Acenocoumarol, amprenavir, anisindione, carbamazepine, cholestyramine, cyclosporine, dicumarol, disulfiram, ergot derivatives, fluorouracil, fosphenytoin, lithium, phenindione, phenobarbital, phenprocoumon, phenytoin, tacrolimus, warfarin.

Rants and Screeds

To quote me, and why not, (Medscape)

They, whoever they are, have long asserted that half of all that is learned in medical school will be found later to not be true. Sure. We learn, things change, medicine advances. Except in the world of alternative medicine, of course, which is as resistant to change as it is data.

One of the interesting variations on the theme is medical myths; ideas that everyone thinks are true but either are disproven or have almost no data to support it. Like alternative medicine, only based in reality.

I thought I knew all the important myths: normal temperature is 98.6, atelectasis causes fevers, gotta double cover Pseudomonas, anaerobes are important in acute aspiration to name a few. I added one this week.

I had a relative with acute diverticulitis who was bemoaning having to forego her nightly glass of wine for fear of the a disulfiram reaction with the metronidazole.

I learned that as a medical student: metronidazole plus alcohol could lead to a degree of vomiting that, if pointed in the right direction, might allow one to levitate.

Like may factoids learned early in my career, I never went back to look at the original literature, and so out of curiosity I went looking to see what the risk really was, mostly since I wanted to have cocktail with my wife, and oh, and I oversharing?

And that literature is a sorry sack of garbage.

The warning against simultaneous use of alcohol and metronidazole appear to be based on laboratory experiments and individual case histories in which the reported reactions are equally likely to have been caused by ethanol alone or by adverse effects of metronidazole. Recent research does not confirm a clinically relevant interaction between ethanol and metronidazole.

The warning is evidently based on animal studies and on a whopping 10 human case reports. On review of these case reprots they found

…no convincing evidence that this reaction exists. Six case reports involving eight patients were evaluated. CONCLUSIONS: Four of the eight cases were serious, including one death, but the authors of all the reports presumed the metronidazole-ethanol reaction to be an established pharmacologic fact. None provided evidence that could justify their conclusions.

And one challege trial found

Metronidazole did not raise blood acetaldehyde or have any objective or subjective adverse effects when used together with ethanol.

“Beer is proof God loves us and wants us to be happy.” Ben Franklin. That’s a myth as well. Franklin never wrote it about beer but wine:

We hear of the conversion of water into wine at the marriage in Cana, as of a miracle. But this conversion is, through the goodness of God, made every day before our eyes. Behold the rain which descends from heaven upon our vineyards, and which incorporates itself with the grapes to be changed into WINE; a constant proof that God loves us, and loves to see us happy!

But the concept is true. For 50 years we have been denying patients a dram happiness while on metronidazole based on virtually nothing.

It is time to stop. Quit telling patients alternative facts unless, of course, you get them from a phone call from the leader of the Boy Scouts. Who, BTW, called me today to say this was the greatest blog ever.

Did I convince my wife? Of course not. Duh.

Je vous renvoie à ce que disoit madame Cornuel, qu’il n’y avoit point de héros pour les valets de chambre, et point de pères de l’Église parmi ses contemporains.

But I did mention this to a colleague who was eventually on metronidazole and he had a drink with no ill consequences.

That’s my N of 1 and I am sticking to it.

Cheers.

Rationalization

In honor of Betteridge's law of headlines: "Any headline that ends in a question mark can be answered by the word 'no'.

Tidsskr Nor Laegeforen. 2014 Sep 16;134(17):1661-3. doi: 10.4045/tidsskr.14.0081. eCollection 2014 Sep 16. [Is combining metronidazole and alcohol really hazardous?]. https://www.ncbi.nlm.nih.gov/pubmed/25223673.

Ann Pharmacother. 2000 Feb;34(2):255-7. Do ethanol and metronidazole interact to produce a disulfiram-like reaction? https://www.ncbi.nlm.nih.gov/pubmed/10676835

Ann Pharmacother. 2002 Jun;36(6):971-4. Lack of disulfiram-like reaction with metronidazole and ethanol. https://www.ncbi.nlm.nih.gov/pubmed/12022894

Pearls

Treatment of choice

Anaerobes, there ain't better. But only strict anaerobes. Treat the microaerophilic organisms with a beta lactam.

Use for

Amebiasis, anaerobic infections, Arthritis, Bacterial vaginosis, Cellulitis, Clostridium difficile-associated colitis, Clostridium infections, crohn's disease, dermatitis - seborrheic, diarrhea, Diverticulosis/itis, Dracunculus medinesis infections, Endocarditis - bacteroides, Endometritis, post-cesarean, E. histolytica, entamoeba polecki, Fasciola hepatica, fistula prophylaxis, Giardia lamblia, gynecological infections, Helicobacter pylori infections, hepatic encephalopathy, inflammatory bowel disease, Intra abdominal infections, Meningitis, ocular rosacea, Osteomyelitis, periodontal disease, pneumatosis coli, Pneumonia, pouchitis, preterm labor - prevention, rheumatoid arthritis, rosacea, Sepsis - anaerobic, surgical prophylaxis, Sweets Syndrome, tonsillitis, Trichomonas vaginalis.

Don't use for

Pregnancy. In pregnancy I mean. Not for pregnancy.

Class

By itself. See. In a class by itself. Humor.