Azithromycin vs. Cephalexin
See how Azithromycin and Cephalexin compare on approved uses, dosing, side effects, and cost.
Key Takeaways
Azithromycin is a macrolide antibiotic typically taken for 3 to 5 days, while cephalexin is a first-generation cephalosporin usually taken for 7 to 14 days with multiple daily doses.
Azithromycin carries FDA warnings for QT interval prolongation and liver toxicity that cephalexin does not share.
Cephalexin is often chosen for skin, bone, and urinary infections, while azithromycin is more commonly used for respiratory infections and certain sexually transmitted infections.
Azithromycin vs. Cephalexin Drug Summary
Azithromycin
Azithromycin is a macrolide antibiotic used to treat respiratory infections, skin infections, and certain sexually transmitted infections. It is usually taken as a short 3 to 5 day oral course, though single-dose regimens exist for some conditions. Its long tissue half-life allows for fewer doses than many other antibiotics.
Cephalexin
Cephalexin is a first-generation cephalosporin antibiotic used to treat respiratory, skin, bone, and urinary tract infections. It is taken orally, usually every 6 to 12 hours for 7 to 14 days depending on the infection. It has been used safely since the early 1970s and remains a common first-choice antibiotic for many outpatient infections.
Azithromycin vs. Cephalexin Side Effects
Azithromycin
Cephalexin
Azithromycin vs. Cephalexin Dosage
Azithromycin
Cephalexin
| STAGE | DOSE | WHEN |
| Starting dose | 500 mg once | Day 1 |
| Maximum dose | 5 mg/kg once daily | Days 2-5 |
| Dose changes | 4 increases | As tolerated |
| STAGE | DOSE | WHEN |
| Starting dose | 25-50 mg/kg/day divided | At the start |
| Maximum dose | 25-50 mg/kg/day divided | Same as starting |
| Dose changes | None | Fixed dose |
Azithromycin
| STAGE | DOSE | WHEN |
| Starting dose | 500 mg once | Day 1 |
| Maximum dose | 5 mg/kg once daily | Days 2-5 |
| Dose changes | 4 increases | As tolerated |
Cephalexin
| STAGE | DOSE | WHEN |
| Starting dose | 25-50 mg/kg/day divided | At the start |
| Maximum dose | 25-50 mg/kg/day divided | Same as starting |
| Dose changes | None | Fixed dose |
Azithromycin vs. Cephalexin Indications
Azithromycin
Azithromycin is FDA-approved to treat a range of bacterial infections including pneumonia, bronchitis, sinusitis, pharyngitis, skin infections, and certain sexually transmitted infections like chlamydia and chancroid. It is also used off-label for traveler's diarrhea and as prophylaxis in select populations exposed to chlamydia. It is not effective against viral infections such as colds or flu.
Community-acquired pneumonia
Acute bacterial sinusitis and bronchitis
Pharyngitis and tonsillitis
Urethritis, cervicitis, and chancroid
Pelvic inflammatory disease and otitis media
Cephalexin
Cephalexin is FDA-approved to treat respiratory tract infections, otitis media, skin and skin structure infections, bone infections, and genitourinary infections including prostatitis. It is also used off-label as an adjunct for acne and for surgical site infection prevention. It is not effective against viral infections such as colds, flu, or COVID-19.
Respiratory tract infections
Otitis media
Skin and skin structure infections
Bone infections
Genitourinary infections including prostatitis
Azithromycin vs. Cephalexin Pros and Cons
Azithromycin
Azithromycin's long tissue half-life allows for very short treatment courses, sometimes just a single dose, which can improve adherence. It also covers atypical respiratory pathogens and several sexually transmitted infections that cephalexin does not treat. It carries FDA warnings for QT prolongation and liver toxicity that require caution in certain patients.
Pros
Short 3 to 5 day or single-dose regimens
Covers atypical respiratory pathogens
Effective against chlamydia and chancroid
Convenient once-daily dosing
Cons
Risk of QT prolongation and heart rhythm effects
Rare but serious liver toxicity warning
More drug interactions via macrolide metabolism
Not indicated for bone infections
Cephalexin
Cephalexin has a long history of safe use since the early 1970s and does not carry a QT prolongation warning. It works well for skin, bone, and urinary infections but requires more frequent dosing over a longer 7 to 14 day course. Patients with penicillin allergy may have some risk of cross-reactivity with this cephalosporin.
Pros
No QT prolongation warning
Long track record of safety since the 1970s
Effective for bone and urinary infections
Fewer major drug interactions
Cons
Requires dosing multiple times daily
Longer 7 to 14 day treatment course
Possible cross-reactivity in penicillin allergy
Not effective against atypical respiratory pathogens
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