Cefixime for Gonorrhea: When an Oral Antibiotic Can Replace the Ceftriaxone Shot

Cefixime for gonorrhea is a fallback, not a substitute for ceftriaxone. The CDC lists cefixime 800 mg taken orally as a single dose as an alternative when ceftriaxone is not available or not feasible. It can be used for uncomplicated urogenital or rectal gonorrhea, but it is not recommended as a reliable alternative for gonorrhea of the throat.

TL;DR: Key takeaways

• Ceftriaxone 500 mg given by intramuscular injection is the CDC's recommended first-line treatment for uncomplicated gonorrhea.
• The current oral alternative is cefixime 800 mg as a single dose when ceftriaxone is not available or feasible, including for uncomplicated urogenital or rectal infection.
• Older pages may still list cefixime 400 mg, but that dose is no longer the current CDC alternative regimen.
• Cefixime is less reliable for gonorrhea of the throat, so it is important to tell a clinician about oral sexual exposure before treatment is chosen.
• Additional treatment depends on your situation: doxycycline may be needed if chlamydia has not been excluded, and follow-up testing recommendations depend on the site of infection and treatment used. Retesting after treatment is recommended because reinfection is common.

Need Help Getting the Right Gonorrhea Treatment? The right treatment depends on where the infection is located, whether you may also have chlamydia, and whether an injection is available or appropriate. An oral antibiotic is not always a substitute for the recommended treatment.

If you have symptoms or think you may have been exposed, try August AI's free symptom checker to evaluate your symptoms in under 2 minutes, or book a $39 online urgent care visit with a US-licensed clinician to discuss your symptoms and next steps.

Cefixime for gonorrhea is a fallback, not a pill version of the shot

Cefixime for gonorrhea is CDC's alternative regimen: 800 mg by mouth, one dose. It is reserved for the situation where ceftriaxone cannot be given, and it covers only urogenital and rectal infection. Ceftriaxone 500 mg as a single intramuscular dose (1 g if you weigh 150 kg or more) remains the only first-line treatment for uncomplicated gonorrhea of the cervix, urethra and rectum.

That hierarchy is pharmacology, not bureaucracy. CDC's 2021 STI Treatment Guidelines are explicit that oral cefixime does not achieve blood levels as high or as sustained as a 500 mg intramuscular dose of ceftriaxone. Same drug family, weaker exposure at the site of infection.

So when people search for oral gonorrhea treatment hoping to trade the needle for a tablet, the honest answer is that the trade is available but it is not neutral. Cefixime is what you use when the injection is genuinely off the table, not what you request because you would rather swallow something.

Cefixime Lost Its First-Line Status in 2012, and That History Still Controls How It's Prescribed

Cefixime is a third-generation oral cephalosporin, the same antibiotic generation as injectable ceftriaxone. It was once a first-line gonorrhea treatment. Then, in 2012, CDC removed oral cephalosporins from its recommended first-line regimens because cefixime susceptibility was declining and treatment failures were being reported. It later returned as a limited alternative when ceftriaxone is not available or feasible.

That history explains its place today. Rising cefixime minimum inhibitory concentrations (MICs) can signal emerging resistance, and CDC has warned that continued reliance on cefixime could add pressure to ceftriaxone susceptibility. That is part of the concern behind super gonorrhea.

A 1991 NEJM comparison reported cure rates of roughly 95% to 98% for single-dose cefixime. Those results were real, but they came from an earlier resistance era and do not mean cefixime is equally reliable against today's circulating gonorrhea strains.

Only four situations really justify gonorrhea treatment without an injection

Gonorrhea treatment without an injection is reserved, not chosen. CDC's phrase "not available or not feasible" resolves to a short list:

1. A ceftriaxone shortage or supply disruption at the treating site.
2. You cannot tolerate or will not accept an intramuscular injection, including needle phobia and bleeding disorder considerations.
3. No clinical setting is available to administer an injection, such as telehealth, express care, or pharmacy-only access.
4. Expedited partner therapy, where CDC clinical care guidance allows a single 800 mg cefixime dose for a partner who cannot be promptly evaluated in clinic. If chlamydial infection has not been excluded, that partner also needs doxycycline 100 mg orally twice daily for 7 days alongside the cefixime.

Three of those four are logistics, not clinical preference. The fourth reason people offer, reported ceftriaxone or penicillin allergy, is the weakest of the set: about 10% of the US population reports penicillin allergy while fewer than 1% have true confirmed allergy, and cross-reactivity with third-generation cephalosporins is rare.

Here is what most pages will not tell you: the appeal of oral gonorrhea treatment is usually convenience, and convenience is the one justification the guidelines do not accept. If you are trying to get gonorrhea treatment online, expect most paths to still end at an in-person injection.

The throat is where cefixime and ceftriaxone stop being interchangeable

Any honest cefixime vs ceftriaxone comparison ends at the throat. CDC puts the cefixime cure rate for pharyngeal gonorrhea at 92.3% (95% CI 74.9% to 99.1%), and that confidence interval is wide enough to include failure rates no one would accept. Ceftriaxone, not cefixime, must be used whenever pharyngeal infection is diagnosed or cannot be ruled out.

This one is partly on you. Pharyngeal gonorrhea is frequently asymptomatic, so "my throat feels fine" rules out nothing at all. Before you agree to the oral option, tell the clinician about any oral sex exposure and ask directly whether a throat swab was collected. If the answer is no, the pill is not an appropriate choice yet.

If a source tells you 400 mg, it is quoting a guideline that changed

Pages quoting cefixime 400 mg for gonorrhea are repeating pre-2012 CDC guidance, not current guidance. The current alternative regimen is cefixime 800 mg orally as a single dose, per the 2021 STI Treatment Guidelines.

The 400 mg figure was the older first-line single dose and the dose used in the foundational 1991 trial literature, which is why it survives in archived pages, older studies and some non-US guidance. It is not a second valid option. It is a fossil.

Separately, cefixime 400 mg once or twice daily belongs to entirely different infections, including respiratory and urinary indications. Never reconstruct a gonorrhea dose from a leftover prescription, and never split, repeat or self-adjust a dose. Confirm the exact number written on your prescription with the prescriber or pharmacist, and read the full drug details for cefixime if the label and the guidance seem to disagree.

A single dose is not the whole treatment, and two more steps are mandatory

If you have read that cefixime plus azithromycin is the gonorrhea regimen, that combination expired. Dual therapy was standard from 2015 to 2020, and CDC dropped it in the 2020 and 2021 update over rising azithromycin resistance and antimicrobial stewardship. What replaces it is narrower: doxycycline 100 mg orally twice daily for 7 days, and only when chlamydial infection has not been excluded. Azithromycin 2 g orally now appears mainly with gentamicin 240 mg IM for true cephalosporin allergy, a regimen that cures only about 80% of pharyngeal infections.

Then two steps that are not optional. A test of cure roughly 7 to 14 days after treatment is expected when an alternative regimen such as cefixime is used, precisely because second-line drugs fail more often. Abstain from sex for 7 days after treatment and until partners have been treated, and plan on retesting for reinfection at about 3 months.

Those dates are easy to lose. A health companion app like August AI can help you log the treatment date, the 7-day mark and the test-of-cure appointment, and ask plain-language questions between visits. It is an adjunct to care, never a clinical decision-maker. August AI does not replace the clinic that ordered the test.

Some symptoms mean a pill is not the right next step at all

Call 911 or your local emergency line, go to an emergency room now if:

• Facial or throat swelling, difficulty breathing, or widespread hives after cefixime or ceftriaxone.
• Fever with joint pain, joint swelling or a spreading rash, which can mean disseminated gonococcal infection.
• Severe lower abdominal or pelvic pain with fever, which can mean pelvic inflammatory disease.

Book a visit within the next week if:

• New testicular pain or swelling, possible epididymitis, and sooner is better.
• Discharge or pain is still present 3 to 5 days after treatment, which needs retesting and a different regimen rather than a repeat dose.
• No test-of-cure appointment has been scheduled.

Talk to a clinician before you start if:

• You have had oral sex since your last test, or your throat was not swabbed.
• You were told you are allergic to penicillin or cephalosporins but were never formally tested.
• You are pregnant.
• You are being offered cefixime only because the clinic is out of ceftriaxone.

The bottom line on choosing the pill over the shot

Cefixime for gonorrhea is a fallback, not a preference. It is 800 mg orally as a single dose, for urogenital and rectal infection only, and only when ceftriaxone truly cannot be given. Confirm three things with your clinician before you accept it: which sites were tested, including the throat; the exact dose and whether any partner drug goes with it; and the date of your test of cure.