The two main concerns are:
- Increases in liver enzymes
- Increase in methotrexate concentrations
I discuss each of these in more detail below.
Both azithromycin and methotrexate are metabolized through the liver and both have been reported to cause increases in certain liver enzymes.
The prescribing information for azithromycin states the following:
Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure have been reported, some of which have resulted in death. Discontinue azithromycin immediately if signs and symptoms of hepatitis occur.
Side effects involving the liver with azithromycin use are uncommon, however.
In clinical trials for the drug, elevated liver enzymes occurred in 4—6% of individuals receiving intravenous therapy. In those taking the drug orally, only 1—2% experienced an increase in liver enzymes. Severe side effects, like liver failure, are thought to be exceedingly uncommon and there are generally other predisposing factors in play.
Methotrexate is more often associated with impaired liver function than azithromycin. Per the prescribing information:
Transient liver function test abnormalities are observed frequently after methotrexate administration and are usually not cause for modification of methotrexate therapy. Persistent liver function test abnormalities, and/or depression of serum albumin may be indicators of serious liver toxicity and require evaluation.
In those taking methotrexate for extended periods of time, periodic liver function tests are recommended (about every one or two months).
Since both azithromycin and methotrexate could potentially cause liver dysfunction, caution is recommended when using them together.
Nevertheless, the concern here is generally in those who already have some sort of liver problem, or are taking additional drugs that may affect liver function.
Some sources state that azithromycin can increase concentrations of methotrexate in the body if taken together.
The serum concentration of Methotrexate can be increased when it is combined with Azithromycin.
This is based on the fact that both methotrexate and azithromycin are metabolized through the liver. Therefore, if used together, the liver may not be able to process them as efficiently. Additionally, if azithromycin alone causes liver dysfunction, methotrexate metabolism may be compromised.
Increases in methotrexate concentrations could theoretically increase the incidence of side effects.
Although azithromycin increasing methotrexate concentrations is possible, it hasn't been seen in clinical studies.
While there is a concern with using azithromycin and methotrexate together, it is mostly based on whether or not either affects liver function.
Use of both in those with normal liver function generally shouldn't cause significant problems, but your liver function should be monitored periodically, especially if you are taking one or both on a long term basis.
Be sure to speak with your doctor regarding any concerns you have regarding the use of methotrexate and azithromycin together. You shouldn't alter your medication regimen at all without first talking with your doctor.
SummaryAzithromycin and methotrexate can cause increases in liver enzymes and potentially decrease overall liver function. Caution is recommended if using both together. In those with normal liver function, the combination has been used safely.
- ^ Azithromycin Prescribing Information. AccessFDA
- ClinicalKey Elsevier ClinicalKey: Azithromycin Monograph.
- AccessFDA Methotrexate Prescribing Information.
- PharmacistAnswers PharmacistAnswers Drug Interaction Checker.
- PubMed Drug interactions with azithromycin and the macrolides: an overview.
- PubMed Pharmacokinetic drug-drug interactions with methotrexate in oncology.