Cephalexin vs. Amoxicillin: Differences, similarities, and which is better for you

Drug overview & main differences | Conditions treated | Efficacy | Insurance coverage and cost comparison | Side effects | Drug interactions | Warnings | Dosages | FAQ

A bacterial infection is caused by an opportunistic overgrowth of bacterial organisms in the body’s tissue or organs. A common condition known as “strep throat” is actually an overgrowth of the bacteria streptococcus pyogenes, sometimes referred to as group A streptococcus, in the throat or on the tonsils. Earaches may be caused by bacteria in the inner or outer ear, and they may lead to fluid build-up and pressure. A toothache could be an abscess of bacteria below the gums. Bacterial infections come in many forms.

Antibiotics are the pinnacle of treatment against bacterial infections. The first antibiotic discovered was penicillin, and it belongs to a group of antibiotics known as beta-lactam antibiotics. Beta-lactams attack the cell wall of bacteria, rendering the bacteria powerless and allowing the body to resolve the infection. Since the discovery of penicillin, there have been many classes and types of beta-lactam antibiotics developed. Cephalexin and amoxicillin are two commonly used beta-lactam antibiotics which have both similarities and differences between them. 

What are the main differences between cephalexin and amoxicillin?

Cephalexin is a prescription medication used to treat a variety of bacterial infections. It is a first-generation cephalosporin antibiotic, which belongs under the larger classification of beta-lactam antibiotics. Cephalexin interferes with cell wall synthesis by binding penicillin-binding proteins inside the cellular wall. Ultimately, when cephalexin is dosed appropriately, it causes lysis, or destruction, or the bacterial cell. Different bacterial types contain different bacterial binding proteins, so cephalexin’s effectiveness varies with different types of bacteria.

Cephalexin is available as an oral tablet or capsule, as well as an oral suspension. The brand name of cephalexin is Keflex. It is used by infants, children, and adults.

Amoxicillin is a prescription medication also used to treat a variety of bacterial infections. It is a penicillin antibiotic but also falls under the larger classification of beta-lactam antibiotics. Amoxicillin, like cephalexin, interferes with cell wall synthesis by binding penicillin-binding proteins inside the cellular wall leading to the destruction of the bacterial cell.

Amoxicillin is available as an oral tablet or capsule, chewable tablet, as well as an oral suspension. The brand name of amoxicillin is Amoxil or Polymox. It is used by infants, children, and adults.

Main differences between cephalexin and amoxicillin
	Cephalexin	Amoxicillin
Drug class	Cephalosporin/ Beta-lactam antibiotic	Penicillin/ Beta-lactam antibiotic
Brand/generic status	Brand and generic available	Brand and generic available
What is the brand name?	Keflex	Amoxil, Polymox
What form(s) does the drug come in?	Tablet, capsule, suspension	Tablet, capsule, chewable tablet, suspension
What is the standard dosage?	500 mg four times daily	500 mg two to three times daily
How long is the typical treatment?	7-14 days	7-14 days
Who typically uses the medication?	Infants, children, adults	Infants, children, adults

Related: Cefdinir vs amoxicillin, Ampicillin vs. amoxicillin

Conditions treated by cephalexin and amoxicillin

Cephalexin has been shown to be active against a variety of bacterial organisms including Escherichia coli, Haemophilus influenzae (beta-lactamase negative), Klebsiella pneumoniae, Moraxella catarrhalis, Proteus mirabilis, Staphylococcus aureus (MSSA), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes. The sensitivity of these organisms allows cephalexin to also be effective in treating many common types of infections including upper respiratory infections such as sinusitis, pharyngitis, and tonsillitis. Amoxicillin is also effective against lower respiratory infections such as community-acquired pneumonia. Other uses of cephalexin include skin infections (cellulitis), bone and joint infections, otitis media, and urinary tract infections (UTI)

Amoxicillin has been shown to be active against a variety of bacterial organisms including Enterococcus faecalis, Escherichia coli, Haemophilus influenzae (beta-lactamase negative), Helicobacter pylori, Proteus mirabilis, Staphylococcus sp., Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes. The sensitivity of these organisms allows amoxicillin to also be effective in treating many common types of infections including upper and lower respiratory infections. Other uses include skin tissue infections, otitis media, and urinary tract infections. 

Both cephalexin and amoxicillin have commonly been used off-label for endocarditis prophylaxis. Patients with congenital heart defects or prosthetic heart valves are at an increased risk of developing an infection in the lining of their heart after dental procedures. Prophylactic doses of antibiotics such as amoxicillin and cephalexin given prior to these procedures have been shown to decrease the risk of such infections.

Conditions treated by cephalexin and amoxicillin
Condition	Cephalexin	Amoxicillin
Upper respiratory infections	Yes	Yes
Pharyngitis	Yes	Yes
Tonsillitis	Yes	Yes
Sinusitis	No	Yes
Community-acquired pneumonia	Yes	Yes
Non-specific lower respiratory infections	Yes	Yes
Cellulitis	Yes	Yes
Impetigo	Yes	No
Otitis media	Yes	Yes
Osteomyelitis	Yes	No
Infectious osteoarthritis	Yes	No
Urinary tract infections	Yes	Yes
Mastitis	Yes	No
Bacterial endocarditis	Off-label	Off-label
Lyme disease	No	Off-label
Dental infections	No	Off-label
H. pylori duodenal ulcer	No	Off-label

Is cephalexin or amoxicillin more effective?

The effectiveness of cephalexin or amoxicillin will vary with each bacteria type and each patient. With any sensitive bacteria, each drug may be effective so long as it is dosed appropriately at the correct intervals. The effectiveness of beta-lactam antibiotics are dependent upon the amount of time that free, non-protein bound drug is above the minimum inhibitory concentration (MIC) of the bacteria.

Another factor in antibiotic therapy is antibiotic resistance. Antibiotic resistance occurs when bacteria changes in response to an exposure to an antibiotic. The change is adaptive to allow it to survive in spite of the antibiotic. In the case of beta-lactam antibiotics, the bacteria produce beta-lactamase enzymes which render the antibiotic ineffective. Repeated or overuse of antibiotics, as well as suboptimal dosing, may contribute to antibiotic resistance.

One study sought to compare the symptomatic relapse in pediatric patients with streptococcal tonsillopharyngitis. This was done by comparing return visits and symptomatic complaints following each type of treatment. The study compared four treatment groups, including amoxicillin and first-generation cephalosporins, including cephalexin. The study found that the incidence of symptomatic relapse was higher in the amoxicillin group than in the first-generation cephalosporin group.

The Infectious Disease Society maintains in its guidelines that amoxicillin is the first choice for group A streptococcal pharyngitis. Cephalexin is an acceptable alternative for patients with a penicillin-related allergy.

Only your doctor can determine which treatment is appropriate for your bacterial infection.

Coverage and cost comparison of cephalexin vs. amoxicillin

Cephalexin is a prescription medication that is covered by both commercial and Medicare drug insurance plans. A typical prescription for cephalexin would be written for 28 capsules of the 500mg strength. The average cash price for this prescription without insurance can be close to $50 or higher. With a coupon from SingleCare, you can get it for less than $9.

Amoxicillin is a prescription medication which is also covered by both commercial and Medicare drug insurance plans. The cash price for a prescription written for 21 capsules of the 500mg strength of amoxicillin is over $20, but with a coupon from SingleCare, you can get this prescription starting around $5.

Cephalexin vs. amoxicillin efficacy
	Cephalexin	Amoxicillin
Typically covered by insurance?	Yes	Yes
Typically covered by Medicare?	Yes	Yes
Standard dosage	28, 500 mg capsules	21, 500 mg capsules
Typical Medicare copay	Typically less than $10, but varies by plan	Typically less than $10, but varies by plan
SingleCare cost	$9-$17	$5-$10

Get the SingleCare prescription discount card

Common side effects of cephalexin vs. amoxicillin

Cephalexin and amoxicillin have a similar list of side effects. The most common side effect of both medications is diarrhea. Other gastrointestinal side effects include nausea, vomiting, and gastritis. In rare instances, cases of pseudomembranous colitis have been reported.

Anaphylactic reactions may happen with both cephalexin and amoxicillin. Anaphylactic reactions are a severe allergic reaction that may present with hives, swelling of the tongue or lips, and/or a restrictive airway. Anaphylactic reactions require immediate medical attention.

The following list is not intended to be a complete list of possible side effects. Please consult a pharmacist, doctor, or another medical professional for a complete list of possible side effects.

Side effects of cephalexin vs. amoxicillin
	Cephalexin		Amoxicillin
Side effect	Applicable?	Frequency	Applicable?	Frequency
Diarrhea	Yes	Not defined	Yes	Not defined
Dyspepsia	Yes	Not defined	Yes	Not defined
Gastritis	Yes	Not defined	Yes	Not defined
Abdominal pain	Yes	Not defined	Yes	Not defined
Nausea	Yes	Not defined	Yes	Not defined
Vomiting	Yes	Not defined	Yes	Not defined
Pseudomembranous colitis	Yes	Not defined	Yes	Not defined
Rash	Yes	Not defined	Yes	Not defined
Urticaria	Yes	Not defined	Yes	Not defined
Dizziness	Yes	Not defined	Yes	Not defined
Headache	Yes	Not defined	Yes	Not defined
Jaundice	Yes	Not defined	Yes	Not defined
Anaphylaxis	Yes	Not defined	Yes	Not defined
Mucocutaneous candidiasis	No	Not defined	Yes	Not defined
Black hairy tongue	No	Not defined	Yes	Not defined

Source: Cephalexin (DailyMed) Amoxicillin (DailyMed)

Clostridium difficile-associated diarrhea

Clostridium difficile-associated diarrhea, referred to as CDAD, is a risk in all antibiotic therapy, including cephalexin and amoxicillin. Patients who present with diarrhea following antibiotic therapy should be evaluated for CDAD, and antibiotic therapy should be discontinued immediately if it is suspected. The severity of CDAD can range from mild diarrhea to severe or fatal colitis. It can happen up to two months after antibiotic therapy is initiated, so it is important to talk to your physician about all recent treatments, even if they are completed.

Clostridium difficile (C. diff) is a component of your gut flora, or the set of microorganisms living in your bowels. Normal bacterial balance keeps C. diff at a safe level, but antibiotic therapy can throw that balance off, leading to an overgrowth of C. diff. The overgrowth leads to inflammation of the gut lining and, typically, diarrhea. In some cases, this can be severe and life-threatening. If you begin to experience unexplained diarrhea and have recently had a course of antibiotics such as cephalexin and amoxicillin, consult with your healthcare provider immediately.

Hypersensitivity reactions and anaphylaxis

Cephalexin and Amoxicillin are both beta-lactam antibiotics and are related to penicillins. Penicillin allergies are among the most common antibiotic allergies, affecting up to 10% of the population. If a patient reports an allergy to penicillins, caution should be used with amoxicillin and cephalexin as well. While most sensitivity, or allergic, reactions are mild and limited to a mild skin rash, there are some who can experience a severe anaphylactic response to beta-lactam antibiotics. A severe reaction would include swelling of the lips, tongue, and throat, and difficulty breathing or swallowing. If you begin to experience any of these symptoms after taking cephalexin or amoxicillin, you should seek medical attention immediately.

Drug interactions of cephalexin vs. amoxicillin

Cephalexin may increase the serum concentrations of the common antidiabetic agent metformin. Most courses of cephalexin are a short duration, so the drugs may be used concurrently as long as the patient is monitored.

Amoxicillin may interfere with the serum concentrations of important immunosuppressants. Serum concentrations of methotrexate have been shown to be increased with concurrent use with amoxicillin, while mycophenolate concentrations may be decreased. These immunosuppressant drugs are used in patients with serious conditions, and therefore patients who require the use of amoxicillin while on these drugs should be monitored closely.

Probenecid, when given with cephalexin or amoxicillin, may increase the serum concentrations of either antibiotic. While the use of both at the same time is not contraindicated, patients should be monitored.

Cephalexin vs. amoxicillin drug interactions
Drug	Drug Class	Cephalexin	Amoxicillin
Metformin	Biguanide, Antidiabetic	Yes	No
Methotrexate	Antifolate, Immunosuppressant	No	Yes
Mycophenolate	Immunosuppressant	No	Yes
Probenecid	Uricosuric	Yes	Yes
Tetracyclines	Antibiotic	No	Yes
Vitamin K	Coagulant	Yes	Yes

Warnings of Cephalexin and amoxicillin

Patients with a penicillin allergy should not take amoxicillin. There is evidence to suggest that patients with a penicillin allergy may also have a cross-sensitivity to cephalosporins, including cephalexin. Caution should be used when prescribing cephalexin in penicillin-allergic patients with no prior use of cephalosporins.

Pseudomembranous colitis is a rare but serious condition. It involves the swelling and inflammation of the colon due to an overgrowth of clostridium difficile. Pseudomembranous colitis can occur with a variety of antibiotics, including cephalexin and amoxicillin.

Cephalexin and amoxicillin are renally excreted. Patients with decreased or impaired renal function must have their doses adjusted accordingly.

Cephalexin is considered pregnancy category B, meaning that animal studies have not shown any teratogenic effects. It is considered generally safe in pregnancy. Cephalexin crosses into breast milk but is generally considered safe while breastfeeding. 

Amoxicillin is also considered pregnancy category B. It is considered generally safe in pregnancy. Amoxicillin crosses into breast milk but is also considered safe while breastfeeding. 

Cephalexin and amoxicillin dosages

Cephalexin and amoxicillin dosing can vary based on several factors. These include the patient’s age, weight, microorganism suspected of infection, and the location of the infection, among other things. As discussed previously, it is important for the serum concentrations of the antibiotic to remain above a specified level for an appropriate period of time to adequately treat an infection. Many clinical trials have been done to form treatment guidelines for various infections in certain populations. Below, we have provided a chart with common dosing for common indications for both cephalexin and amoxicillin. Please note that children’s dosing is weight-based. This is not intended as medical advice. Your prescriber will recommend the appropriate drug and dose based on their assessment. 

Cephalexin and amoxicillin dosages
	Cephalexin		Amoxicillin
Indication	Pediatric dose	Adult dose	Pediatric dose	Adult dose
Upper respiratory infection	25 to 50 mg/kg/day divided in 2 to 4 doses for 7 to 14 days	250 mg every 6 hours or 500 mg every 12 hours for 7 to 14 days	Not indicated	Not indicated
Group A strep pharyngitis and tonsillitis	20 mg/kg/dose every 12 hours for 10 days	500 mg every 12 hours for 10 days	50 mg/kg/dose once daily or 25 mg/kg/dose every 12 hours for 10 days	1000 mg once daily or 500 mg every 12 hours for 10 days
Lower respiratory infections (LRI)	25 to 50 mg/kg/day divided in 2 to 4 doses for 7 to 14 days (mild/moderate) or 50 to 100   mg/kg/day divided in 2 to 4 doses for 7 to 14 days (severe)	250 mg every 6 hours or 500 mg every 12 hours for 7 to 14 days	45 mg/kg/day divided every 12 hours or 40 mg/kg/day divided every 8 hours	500 mg every 8 hours or 875 mg every 12 hours for 10 days
Skin infections (unspecified)	25 to 50 mg/kg/day divided in 2 to 4 doses for 7 to 14 days	250 mg every 6 hours or 500 mg every 12 hours for 7 to 14 days	Not indicated	Not indicated
Cellulitis (nonpurulent)	25 to 50 mg/kg/day divided in 4 doses for 5 to 14 days	500 mg  every 6 hours for 5 to 14 days	20 mg/kg/day in divided doses every 8 hours or 25 mg/kg/day in divided doses every 12 hours for 5 to 14 days	250 mg every 8 hours or 500 mg every 12 hours for 5 to 14 days (mild/moderate) or 500 mg every 8 hours or 875 mg every 12 hours for 5 to 14 days (severe)
Skin abscess (purulent)	25 to 50 mg/kg/day divided in 4 doses for 5 to 10 days	500 mg  every 6 hours for 5 to 14 days (plus incision and drainage)	Not indicated	Not indicated
Urinary tract infection (UTI)	25 to 50 mg/kg/day divided in 2 to 4 doses for 7 to 14 day	250 mg every 6 hours or 500 mg every 12 hours for 7 to 14 days	20 mg/kg/day in divided doses every 8 hours or 25 mg/kg/day in divided doses every 12 hours	500 mg every 12 hours or 250 mg every 8 hours

Frequently asked questions about cephalexin vs. amoxicillin

What is cephalexin?

Cephalexin is a first-generation, cephalosporin antibiotic. It belongs to a bigger classification of antibiotics known as beta-lactam antibiotics. It is generally effective against bacteria involved in upper and lower respiratory tract infections, otitis media, mastitis, and skin, bone, and joint infections.

What is amoxicillin?

Amoxicillin is a penicillin-derivative antibiotic. It belongs to a bigger classification of antibiotics known as beta-lactam antibiotics. It is generally effective against bacteria involved in upper and lower respiratory tract infections, otitis, media, and skin infections.

Are Cephalexin and amoxicillin the same?

While cephalexin and amoxicillin are beta-lactam antibiotics, they are not the same. Cephalexin is a cephalosporin antibiotic, and amoxicillin is a penicillin derivative. While they cover some of the same bacterial organisms, they each cover unique organisms.

Is cephalexin or amoxicillin better?

There are many factors to choosing the most effective antibiotic for any infection. While one study showed that amoxicillin may be associated with more relapses of strep pharyngitis versus cephalexin, it remains in the treatment guidelines as the first-line treatment.

Can I use cephalexin or amoxicillin while pregnant or breastfeeding?

Cephalexin and amoxicillin are considered safe during pregnancy. There is no known harm to the fetus despite the fact that both drugs cross the placenta. Cephalexin is excreted into breast milk. Breastfed infants experienced diarrhea and discomfort. Amoxicillin has also been shown to be excreted into breast milk. Incidences of diarrhea, rash, and somnolence in breastfed infants have been reported with amoxicillin. With either drug, the benefit of treatment in the mother must be weighed against the risk of adverse events in the infant.

Can I use cephalexin or amoxicillin with alcohol?

While there is no contraindication to taking these antibiotics while consuming alcohol, patients should be aware that alcohol consumption may increase the risk of gastrointestinal side effects. 

Is cephalexin or amoxicillin stronger?

When dosed appropriately, both antibiotics are effective against their covered organisms. The organism coverage of cephalexin makes it effective in some conditions that amoxicillin is not, including mastitis and bone and joint infections.

How quickly does cephalexin work?

Antibiotics begin working against the organism as soon as you begin therapy. It may take several days before a patient begins to experience symptomatic relief depending on the type of infection.

Is amoxicillin or cephalexin better for ear infections?

The American Academy of Family Physicians (AFP) maintains in its guidelines that amoxicillin is the treatment of choice for otitis media. Other antibiotics, like cephalosporin, may be used when there is an allergy or if resistance is suspected.

What infections does cephalexin treat? / What is cephalexin most commonly used for?

Cephalexin is useful in a wide variety of infection types. At the appropriate dose, cephalexin is effective in treating many respiratory infections. Group A streptococcal pharyngitis, tonsillitis, lower respiratory tract infections, and community-acquired pneumonia are among the respiratory infections which respond to cephalexin. Cephalexin is also very useful in skin and soft tissue infections such as cellulitis, impetigo, incision site infections, and abscesses. Cephalexin has a relevant place in therapy amongst other infection types such as urinary tract infections and mastitis. Your healthcare provider can help determine if cephalexin is the appropriate antibiotic for you.