School Lady asked
Hello, I stopped taking my Atorvastatin Tabs 80Mg after being prescribed to take Azithromycin Tablets 250 mg at a Walk-In Clinic. I took my last antibiotic tablet on Friday, July 13, 2018. So it has now been 24 days. So is it safe to go back to taking the 80Mg Atorvastatin Tabs without being worried about a drug interaction? Or, should I wait longer? Thank you for your answer and help!
Answer
There is a potentially significant interaction between azithromycin, the antibiotic in the Z-Pak, and Lipitor (atorvastatin), a 'statin' cholesterol drug. However, data is conflicting in regard to just how risky the combination is. Nevertheless, they generally shouldn't be taken together unless both are prescribed by your doctor so you can be appropriately monitored.
What Is The Interaction?
Azithromycin is in a family of antibiotics known as macrolides. Many macrolides (which also includes clarithromycin and erythromycin) are known to strongly inhibit a liver metabolizing enzyme known as CYP3A4, a major metabolizing enzyme in the body (1).
Lipitor (atorvastatin) is metabolized in our bodies by this enzyme (CYP3A4). If this enzyme is inhibited, it won't metabolize Lipitor as quickly, potentially increasing levels in the body. With higher levels of the drug, the risk of side effects goes up.
The side effect we are most concerned about is a rare but serious condition known as rhabdomyolysis, which is characterized by accelerated breakdown, often painful, of skeletal muscle (2).
The prescribing information for Lipitor warns of co-administration with CYP3A4 inhibitors (3):
"LIPITOR is metabolized by cytochrome P450 3A4. Concomitant administration of LIPITOR with strong inhibitors of CYP 3A4 can lead to increases in plasma concentrations of atorvastatin. The extent of interaction and potentiation of effects depend on the variability of effect on CYP 3A4."
It goes on to give an example study of co-administration with Lipitor and clarithromycin, a strong CYP3A4 inhibitor (and a macrolide incidentally):
"Clarithromycin: Atorvastatin AUC [area under the curve] was significantly increased with concomitant administration of LIPITOR 80 mg with clarithromycin (500 mg twice daily) compared to that of LIPITOR alone. Therefore, in patients taking clarithromycin, caution should be used when the LIPITOR dose exceeds 20 mg."
To avoid potential interactions, it is often recommended to "hold" or not take Lipitor during the entire duration of therapy with a strong CYP3A4 inhibitor (4).
Data Between Lipitor And Azithromycin
We know there is a definitive interaction between Lipitor and CYP3A4 inhibitors, but a specific interaction with azithromycin is less clear.
Although azithromycin is a 'macrolide', it is not extensively metabolized by CYP3A4 and is not known to be a strong inhibitor (5). There are numerous studies that suggest that azithromycin administration is safe with Lipitor due to this. One study concluded the following:
"These data suggest that while azithromycin appears to be safe to coadminister with [Lipitor] atorvastatin, clarithromycin should be avoided in patients taking this and similarly metabolized HMG‐CoA inhibitors."
Conflicting with this data is a report from the World Health Organization that produced results indicating that azithromycin does increase the risk of rhabdomyolysis with statin drugs like Lipitor (6). Therefore, individuals on the combination should be appropriately monitored, just to be safe.
How Long To Wait Between Lipitor And Azithromycin?
There is no definitive time table that has been reported in regard to how long to wait between doses of Lipitor and azithromycin to avoid or reduce the risk of a potential interaction.
Unfortunately, in this case, the half-life (time it takes our bodies to metabolize 50% of a drug) of azithromycin is long, around 60-70 hours. It will take nearly 10-14 days for azithromycin to completely be eliminated from the system. To avoid both in your system at the same time, you would need to wait that amount of time.
As mentioned earlier in this article, it is relatively common to take a short "break" on a "statin" drug like Lipitor if it is prescribed with a strong CYP3A4 inhibitor or other interacting medication. There are many additional factors to consider however when determining if you should, or for how long, 'hold' your Lipitor, such as:
- Medical history
- Cardiovascular risk
- Age (>65 at higher risk)
- Kidney and liver function
- Thyroid levels
As there are many considerations, you should speak with your doctor regarding the best course of action for your medical situation.
