Why Do You Take Two Tablets Of Azithromycin On Day One?
The pharmacist discusses why it is necessary to take a "loading dose" of two tablets of azithromycin on day one of therapy with the Z-Pak.

Question
Is my Z-pack less effective if I only took tablet one at the start? I know the directions tell me to take two tablets for my first dose, but I don't understand why I would need to.

Answered by Dr. Brian Staiger, PharmD
Medical Content Reviewed By HelloPharmacist
Staff
Last updated Apr 03, 2025
Key points
- A Z-Pak contains 5 daily doses of azithromycin. Two tablets are taken at the same time on 'day 1' for your first dose, then one tablet is taken daily for the next four days.
- Taking two tablets on 'day 1' acts as a loading dose, and allows the drug to reach high enough concentrations in your body to work against the bacteria causing your infection.
- Only taking one tablet, instead of two, on your first day, may make the medication less effective, as it may not reach high enough concentrations in your body to be effective.
The Z-Pak (azithromycin 250mg tablets) is one of the most commonly prescribed antibiotics and is used for a variety of infections, including:
- Bronchitis
- Sinusitis (e.g sinus infection)
- Ear infections
Unlike the dosing for many other antibiotics, if you've been prescribed a Z-Pak, you'll notice that the directions state to take two tablets by mouth at the same time for your first dose.
It is important you follow these directions to get the best effects of the medicine as it allows the drug to reach concentrations high enough in your body to adequately fight your infection. I discuss this more in the sections below.
Z-Pak Dosing
The dosing of the Z-Pak is as follows:
- Take two tablets (500 mg), at the same time, on the first day of therapy
- Take one tablet (250 mg) once daily for 4 days thereafter
The total duration of therapy is 5 days.
Why The Z-Pak Has A 'Loading Dose'
It is very important that you take two tablets (500 mg) at the same time, for your first dose of your Z-Pak.
This 500 mg dose acts as a "loading dose" and allows the medication to reach high enough concentrations in your body to kill the infection-causing bacteria.
Well, quick side note here.
I do want to point out that azithromycin, for the most part, is 'bacteriostatic', meaning it works by inhibiting the replication of the bacteria, so it doesn't directly destroy them. Only at very high doses does it 'kill' bacteria (i.e. 'bacteriocidal').
Now, azithromycin has a somewhat unusual characteristic relative to other antibiotics in that it has an extremely long-half life (around 68 hours), meaning that each dose lasts for days in the body.
That loading dose you take quickly gets you to the sufficiently high azithromycin levels you need in your body to be effective, and that high concentration is maintained with the 250 mg daily doses for the next four days.
Per the prescribing information for azithromycin:
"With a regimen of 500 mg on Day 1 and 250 mg/day on Days 2-5, Cmin [miniumum concentrations] and Cmax [maximum concentrations] remained essentially unchanged from Day 2 through Day 5 of therapy. However, without a loading dose, azithromycin Cmin concentrations required 5 to 7 days to reach steady-state."
Overall, if you do not take a loading dose, the concentrations of azithromycin may not reach high enough levels during your course of therapy to be effective. That is why the loading dose is so important.
Final Words
Thanks again for reaching out.
As I hope I've answered here, it's important to emphasize that the loading dose of azithromycin is important.
If you don't take a loading dose, you will experience lower concentrations of the drug, which may not be effective, and therapy will most likely need to be lengthened to eliminate your infection.
If you accidentally took one tablet (250 mg) instead of two (500 mg), you should talk to your doctor as they may alter your therapy to ensure effectiveness.
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Dr. Brian Staiger, PharmD
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