Amoxicillin vs. Penicillin: What’s the Difference?

Amoxicillin and penicillin (also known as penicillin V potassium or penicillin G) are two of the most widely-prescribed antibiotics across the globe.

And from their inception, it’s estimated that millions of lives have been saved due to their effective treatment of bacterial infections, including respiratory tract infections like pneumonia or bronchitis.

Amoxicillin and penicillin share a similar chemical structure and work the same way to kill bacteria, so they help treat some of the same types of diseases.

However, there are a few differences in their indications—the specific infections each drug is approved by the Food and Drug Administration (FDA) to treat.

Penicillin generally treats mild to moderate conditions, whereas amoxicillin may treat certain severe infections.

Read on for an in-depth comparison of amoxicillin versus penicillin, including an overview of their uses, dosing, side effects, potential for interaction, and more.

Primary Differences: Amoxicillin vs. Penicillin

The FDA has approved amoxicillin and penicillin to treat similar types of bacterial infections. Both drugs are prescribed to treat certain bacterial infections of the ears, nose, throat, urinary tract, skin, and lower respiratory tract.

Examples of bacteria considered susceptible to either amoxicillin or penicillin include certain Streptococcus and Staphylococcus species.

In addition, amoxicillin is prescribed as part of a combination drug regimen to treat a stomach infection called pylori Helicobacter (H. pylori) and duodenal ulcer disease. Penicillin is not approved to treat H. pylori.

Due to widespread use and overuse, many bacterial infections that were previously treatable with penicillin are now resistant to its effects.

In general, fewer bacteria are resistant to amoxicillin compared to penicillin. However, some bacteria historically treated with amoxicillin may no longer respond to this drug.

Considering recent trends in your area, a healthcare provider can determine which antibiotics may be suitable for treating your infection.

Amoxicillin

Amoxicillin is an antibiotic that belongs to the beta-lactam drug class. It is considered an amino-penicillin, meaning it was synthetically developed by making slight chemical alterations to penicillin.

Amoxicillin is a generic prescription drug. Brand-name versions include Amoxil and Larotid.

Like penicillin, the FDA has approved amoxicillin to treat infections caused by certain types of bacteria in the ears, nose, throat, urinary tract, skin, and lower respiratory tract.

Additionally, amoxicillin is prescribed to treat H. pylori and duodenal ulcer disease as part of a combination drug regimen.

It is also commonly prescribed to prevent bacterial endocarditis associated with dental procedures.

Finally, used with other drugs, amoxicillin is one of the two active ingredients in the brand-name antibiotic Augmentin, which contains amoxicillin and clavulanate acid and can be used for hard-to-treat sinus and ear infections.

Penicillin

Penicillin is also classified as a beta-lactam antibiotic.

It is also the first and only naturally-occurring antibiotic. Scientists later developed other antibiotics by making minor changes to the chemical structure of penicillin.

Penicillin is a generic prescription drug. There currently isn’t a brand-name version of penicillin V potassium available.

Penicillin works to treat many of the same infections as amoxicillin. Specifically, the FDA has approved penicillin to:

• Treat mild to moderate Streptococcal infections of the respiratory tract, such as strep throat
• Treat mild to moderate Pneumococcal infections of the respiratory tract, such as pneumonia
• Treat mild to moderate Staphylococcal infections of the skin
• Treat certain infections of the mouth or throat, such as gingivitis and pharyngitis
• Prevent the recurrence of rheumatic fever

Conversely, penicillin G (an injected form of penicillin that contains potassium and sodium) can be used to treat the following infections:

• Endocarditis: Infection of the inner lining of the heart chambers or valves. 
• Pericarditis: Infection of the tissues around the heart. 
• Haverhill fever: Infection caused by bites or scratches from rats.
• Sepsis: A condition where bacteria enter the bloodstream. 

Before choosing penicillin as an antibiotic to treat a specific infection, healthcare providers typically order lab tests to identify the bacteria responsible for the condition.

Tests can also help determine if penicillin or another antibiotic will be effective against the bacteria.

Which Is More Effective?

Given the similar nature of amoxicillin and penicillin, only some clinical studies have directly compared the two medications. 

An older study investigated the difference between oral amoxicillin and injectable penicillin for pneumonia in children.

The research showed that a similar percentage of participants (81%) in both the penicillin and amoxicillin groups were successfully cured of infection, suggesting similar effectiveness of the two drugs.

Another study compared the effectiveness of amoxicillin vs. penicillin for tonsillitis.

After a 10-day course of either medication, 76% of the participants who took amoxicillin achieved treatment success, compared to 64% of those who took penicillin.

In this study, researchers found amoxicillin more effective than penicillin for tonsillitis.

Overall, these studies suggest relative efficacy between the two products. However, amoxicillin may provide better outcomes for certain infections or strains of bacteria.

Dosage

Both amoxicillin and penicillin are available in a variety of dosage forms and strengths.

When selecting a dosage form, healthcare providers consider several factors, such as personal preferences and the ability to swallow pills or liquids.

No differences in effectiveness exist between the various dosage forms of the same medication.

A healthcare provider may prescribe amoxicillin in the following forms and strengths:

• Amoxicillin oral capsule: 250 milligrams (mg) or 500 mg
• Amoxicillin oral tablet: 500 mg or 875 mg
• Amoxicillin chewable tablet: 125 mg or 250 mg
• Amoxicillin oral liquid suspension: 50 milligrams per milliliter (mg/mL), 125 mg/5 mL, 200 mg/5 mL, 250 mg/5 mL, or 400 mg/5 mL

Penicillin V potassium is available in the following forms and strengths:

• Penicillin oral tablets: 250 mg or 500 mg
• Penicillin oral liquid suspension: 125 mg/5 mL or 250 mg/5 mL

The dosing recommendations for amoxicillin and penicillin vary depending on the person’s age, weight, type of infection, and severity.

These factors also influence the frequency (number of doses per day) and duration (number of days) of treatment with amoxicillin or penicillin.

Typical dosages of amoxicillin and penicillin are:

• Amoxicillin: 250 to 875 mg two or three times daily (every 8 to 12 hours), typically for 10-14 days 
• Penicillin: 125 to 500 mg three or four times daily (every six to eight hours), typically for seven to 14 days

Depending on individual factors, a healthcare provider may prescribe a dosage outside these ranges. Follow the direction of a healthcare provider and take amoxicillin or penicillin exactly as prescribed.

You shouldn’t stop treatment early, even if your symptoms go away. Doing so can increase the risk of the infection returning even worse, making it more challenging to treat.

Storage Requirements

Amoxicillin and penicillin share similar storage requirements. Still, these vary with the dosage form:

Oral capsules and tablets: Keep in a cool, dry area at room temperature in a sealed container.

Oral liquid suspension: Pharmacies store these products in bottles of powder kept at room temperature. After the pharmacist mixes the powder with water, storing the liquid suspension in the refrigerator is recommended. Note the expiration date that your pharmacist adds to the label.

After the product is mixed with water, it usually expires 10 or 14 days later—you should not take the medication after the expiration date.

Side Effects & Safety

Like all drugs, amoxicillin, and penicillin may cause similar side effects. As such, closely monitor yourself or a loved one while taking amoxicillin or penicillin.

If you feel any of the side effects listed below continue to worsen or affect your ability to complete your prescription, contact your healthcare provider immediately.

Common Side Effects

The more common side effects are usually mild and temporary, such as:

Severe Side Effects

In rare instances, treatment with amoxicillin or penicillin leads to severe, longer-lasting diarrhea, known as Clostridioides difficile (C. Diff).

This can occur when antibiotics kill the “good” bacteria in your digestive tract and protect it from harmful overgrowth of “bad” bacteria. In these cases, diarrhea could last up to two months and require treatment.

Taking amoxicillin or penicillin infrequently leads to a severe allergic reaction called anaphylaxis. Symptoms of an allergic reaction include rash, difficulty breathing, and swelling in the face or throat.

Potential for Interaction

Other medications may interact with amoxicillin or penicillin, resulting in side effects or decreased effectiveness.

Some drugs that interact with amoxicillin and penicillin include:

Before starting amoxicillin or penicillin, talk to a healthcare provider about other medications you take.

Sharing this information with your pharmacist can also help prevent interactions that may be dangerous.

Other Safety Considerations

Individuals with a history of amoxicillin or penicillin allergy should not receive either medication.

Before starting penicillin or amoxicillin, talk to a healthcare provider if you have an allergy or a history of a reaction to a similar drug.

Regarding pregnancy, no adequate and well-controlled studies show conclusively that the potentially harmful effects of penicillin or amoxicillin on a fetus can be ruled out.

Therefore, amoxicillin and penicillin should only be used in pregnant people if needed.

Additionally, healthcare providers try to avoid prescribing amoxicillin to people with a history of mononucleosis or “mono” due to a risk of skin reactions.

Summary

Penicillins are a class of antibiotics used against a wide range of bacteria. Both penicillin and amoxicillin are categorized as penicillin-class drugs.

Because of this, the two medications work similarly and are used to treat similar conditions.

Prescribed for conditions such as bacterial infections of the ears, nose, throat, urinary tract, skin, and lower respiratory tract, the varied uses of these two drugs have saved millions of lives since the inception of penicillin in 1941.

Nonetheless, like all drugs, a healthcare provider should decide how and when to use these medications, as their fundamental differences, most notably amoxicillin’s effectiveness against more types of bacteria, may determine which antibiotic a healthcare provider prescribes to treat an infection.