Doxycycline vs Amoxicillin: Everything you need to know!

Although doxycycline and amoxicillin are both antibiotics, they are very different drugs. From having different mechanisms of action, indications, side effects, drug interactions, dosing, and pharmacokinetics, these two antimicrobials are not interchangeable. 

Because doxycycline is a bacteriostatic tetracycline and amoxicillin is a bactericidal beta-lactam, they are each better suited to handle different types of infections. Most notably, doxycycline is the antibiotic of choice to treat Rickettsial infections and amoxicillin is labeled to treat ear, nose, and throat infections. 

Their different drug classes and mechanisms of actions also means that they have different side effects, with doxycycline’s unique side effects including tooth discoloration and photosensitivity and amoxicillin’s hypersensitivity reactions.    

What is doxycycline?

Doxycycline is a second generation tetracycline-class antimicrobial agent approved by the Food and Drug Administration (FDA) to be prescribed for Rickettsial infections, sexually transmitted infections, respiratory tract infections, specific bacterial infections, ophthalmic infections, anthrax exposure, as alternative treatment for selected infections when penicillin cannot be taken, adjunctive therapy in acute intestinal amebiasis and severe acne, and malaria prophylaxis.1 

As a tetracycline, it inhibits protein synthesis by binding to the 30S ribosomal subunit and is bacteriostatic, meaning that this agent prevents the growth of bacteria rather than directly killing bacteria.  

Oral doxycycline is absorbed almost completely and therefore side effects to the lower bowel such as diarrhea are not common.1 However, upper gastrointestinal, skin, and renal side effects have been reported more frequently. Specifically, patients taking medications right before bed are more likely to experience esophagitis and esophageal ulcerations. 

This adverse effect can be mitigated by taking the tablet or capsule with adequate amounts of fluid to wash down the dose.1 Other side effects are nausea, vomiting, diarrhea, rashes, and a rise in blood urea nitrogen.

Notable severe side effects include tooth discoloration, pseudomembrane colitis, and photosensitivity. Using tetracyclines like doxycycline during the period of tooth development such as the latter half of pregnancy, infancy, and childhood up to 8 years old, may lead to permanent yellow-gray discoloration of the teeth.2

 Tooth discoloration is most commonly seen in patients who use doxycycline for an extended period of time, but it has also been seen if patients use it over repeated short-term courses. This is due to the ability of tetracyclines to be incorporated into calcifying tissues, resulting in discoloration depending on the dose or type of drug in relation to body weight. 

Therefore, it is recommended that tetracyclines not be used in the aforementioned age groups unless it is being used to treat post-exposure anthrax. Clostridium difficile is a bacteria known to potentially cause diarrhea or potential fatal colitis after use of antibacterial agents. The use of these agents alters the bacterial composition of the gastrointestinal tract, and therefore may allow pathogenic bacteria such as C. diff to grow. Photosensitivity presents as a burning or painful sunburn reaction in patients exposed to either direct sunlight or ultraviolet light.3         

What is amoxicillin?

Amoxicillin is a semisynthetic bactericidal antibiotic that is an analog of ampicillin and has broad spectrum activity against many gram-positive and gram-negative bacteria. As a beta-lactam, this aminopenicillin functions by competitively inhibiting penicillin binding proteins to prevent bacterial cell wall synthesis. 

This inhibition leads to lysis by autolytic enzymes and eventually bacterial cell death. This antimicrobial is indicated to be used for the infections of the ear, nose, throat, genitourinary tract, skin, lower respiratory tract, and uncomplicated gonorrhea caused by specific organisms. 

Amoxicillin comes in the dosage forms of capsules, tablets, chewable tablets, powder for oral suspension, and pediatric drops for oral suspension. 

Infection locationOrganisms susceptible to amoxicillin
Ear, nose, and throatStreptococcus spp. (α- and β-hemolytic strains only), S. pneumoniae, Staphylococcus spp., or H. influenzae
Genitourinary tractE. coli, P. mirabilis, or E. faecalis
Skin and skin structureStreptococcus spp. (α- and β-hemolyticstrains only), Staphylococcus spp., or E. coli.
Lower respiratory tractStreptococcus spp. (α- and β-hemolyticstrains only), S. pneumoniae, Staphylococcus spp., or H. influenzae
Acute, uncomplicated gonorrheaN. gonorrhoeae

It is important to note that some patients on penicillin therapy may experience severe anaphylactic reactions, which is more frequently seen in patients on parenteral penicillin therapy. 

These reactions are more likely to be experienced by patients with a history of penicillin hypersensitivity. Patients considered to be at low-risk for an anaphylactic reaction include those with only a family history, those with isolated non allergic symptoms like gastrointestinal symptoms, pruritus without a rash, or unknown reactions without features of an IgE-mediated reaction.4 

Moderate-risk patients have had urticaria or other pruritic rashes and reactions including features of an IgE-mediated reaction.4 High-risk patients who have had anaphylaxis, positive penicillin skin testing, or hypersensitivities to multiple other β-lactam antibiotics should avoid receiving amoxicillin.4 Adverse reactions include mucocutaneous candidiasis, nausea, vomiting, diarrhea, a moderate rise in liver enzymes, crystalluria and anemia. 

Doxycycline vs amoxicillin

How are doxycycline and amoxicillin different?

DoxycyclineAmoxicillin
Antimicrobial ClassTetracyclineBeta-lactam
Mechanism of ActionInhibit protein synthesis by binding to bacterial subunitsInhibit bacterial cell wall synthesis by binding to penicillin-binding proteins
IndicationsAnthrax exposure, cholera, respiratory tract infections, Rickettsial infections, zoonotic infectionsEar, nose, and throat infections, H. pylori eradication, lower respiratory tract infections, urinary tract infections
Side effectsBone growth suppression, photosensitivity, dental discolorationHypersensitivity reactions, C. difficile associated diarrhea
Drug InteractionsAnticoagulant therapy, antacids, barbiturates, carbamazepine, phenytoinProbenecid, chloramphenicol, macrolides, sulfonamides, tetracyclines, estrogen/progesterone contraceptives
Dosing100 to 200 mg/day in 1 to 2 divided dosesImmediate release: 500 mg to 1 g every 8 to 12 hours.
Extended release: 775 mg once daily.

Doxycycline vs amoxicillin: Side effects

The more common side effects seen for amoxicillin include diarrhea, headache, skin rash, and vaginal yeast infections. For doxycycline, the most common side effects are headache, nausea, vomiting, and skin sensitivity to sunlight, otherwise known as photosensitivity.

Dosage of doxycycline and amoxicillin

The dosage required to achieve the desired therapeutic effect for doxycycline is lower than that of amoxicillin. The standard dosage for immediate release formulations and most extended-release formulations of doxycycline are 100 to 200 mg/day in 1 to 2 divided doses. 

For amoxicillin, the immediate release dosage is 500 mg to 1 g every 8 to 12 hours while the extended-release dosage is 775 mg once daily. This variation in dosing can be attributed to the different half-lives of each drug. 

Doxycycline has an extended half-life of 18-22 hours whereas amoxicillin has a much shorter half-life of 61.3 minutes for the immediate release formulation and 90 minutes in the extended-release formulation. 

Amoxicillin’s shorter half-life necessitates a higher dose taken more frequently than doxycycline. As amoxicillin is greatly renally excreted, unlike doxycycline, dosing needs to be adjusted according to altered kidney function. 

Warnings of doxycycline and amoxicillin

The main concern in patients taking doxycycline is the permanent teeth discoloration that can occur if taken during the period of tooth development, C. diff-associated diarrhea, photosensitivity, and overgrowth of non-susceptible organisms. 

For amoxicillin, fatal anaphylactic reactions have been reported and required immediate emergency treatment with epinephrine, oxygen, intravenous, steroids, and airway management.

Drug interactions with doxycycline and amoxicillin

Patients taking amoxicillin should be aware that probenecid decreases the renal tubular secretion of amoxicillin and may result in increased and prolonged levels of amoxicillin in the blood. 

Other antibiotics such as chloramphenicol, macrolides, sulfonamides, and tetracyclines may interfere with the bactericidal effects of penicillin. Since amoxicillin may affect the gastrointestinal flora, this may lead to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives. 

Patients taking doxycycline who are also on anticoagulant therapy may need to decrease their anticoagulant dosage, avoid taking penicillin at the same time, and take into consideration that concurrent use of tetracycline may render oral contraceptives less effective. 

The absorption of doxycycline may be impaired by antacids containing aluminum, calcium, magnesium, bismuth subsalicylate and iron. Doxycycline’s half-life is decreased by barbiturates, carbamazepine and phenytoin.

Which is better: doxycycline or amoxicillin?

There is no definitive answer as to whether doxycycline or amoxicillin is better. The preferable antibiotic depends on many factors, but mainly the patient’s personal situation such as allergies or what the patient is infected with. 

For example, if the patient has a severe penicillin allergy, it would be preferable for them to take doxycycline instead of amoxicillin. However, doxycycline and amoxicillin are each first-line therapy for specific conditions. 

Doxycycline is the preferred antibiotic to treat tick borne infections such as Lyme disease and amoxicillin is first-line for children with acute otitis media since it is effective against most Strep. pneumoniae strains, safe for most patients, and is an affordable option.5,6

When should you consult a doctor?

If you experience certain severe side effects when taking either drug, you should call your doctor right away. Specifically for amoxicillin, if you experience signs of an allergic reaction, unexplained bruising or bleeding, fever or chills, or vaginal itching or discharge, you should inform your physician as soon as possible. 

Some of these signs may also be seen in patients taking doxycycline and are of concern. Signs of an allergic reaction, signs of liver problems such as dark urine, feeling tired, or not hungry, signs of pancreas problems such as bad stomach or back pain, or chest pain are all reasons that you should call your doctor.

How can DrHouse help you?

If you have contracted a bacterial infection, and are unsure of the best course of action to take, the clinicians at DrHouse can determine the best antibiotics for you. During treatment, if you experience any unpleasant or worrisome side effects, the online medical professionals at DrHouse can also address your concerns.

Key Takeaways

Doxycycline and amoxicillin are both antimicrobial agents, but are very different in many regards. As seen throughout this article, these antibiotics work through different mechanisms and as a result are each better suited for specific infections. 

Patients can expect to experience different side effects from each drug and certain medications you may be taking concomitantly may be of concern. Therefore, it is important to be transparent with your doctor about all medications, both over-the-counter and prescription, that you are taking. 

As both of these medications are antibiotics, it is important to finish the full course of the medication regardless of whether you feel better to prevent antibiotic resistance.

Sources:

  • 1. Doryx (doxycycline hyclate) package insert. Salisbury South, South Australia. Mayne Pharma International Pty Ltd; 1967. Revised 2008 June.
  • 2. Sánchez, Andrés, et al. “Tetracycline and other tetracycline-derivative staining of the teeth and oral cavity.” Int J Dermatol, vol. 43,10 (2004): 709-715. Doi: https://www.doi.org/10.1111/j.1365-4632.2004.02108.x
  • 3. Drucker, Aaron and Rosen, Cheryl. “Drug-induced photosensitivity: culprit drugs, management and prevention.” Drug Saf, vol. 34,10 (2011): 821-837. Doi: https://www.doi.org/10.2165/11592780-000000000-00000
  • 4. Shenoy, Erica, et al. “Evaluation and Management of Penicillin Allergy: A Review.” JAMA, vol. 21,2 (2019): 188-199. doi: https://www.doi.org/10.1001/jama.2018.19283
  • 5. Sanchez, Joyce. “Clinical Manifestations and Treatment of Lyme Disease.” Clin. Lab. Med, vol 25,4 (2015): 765-778.
  • 6. Ramakrishnan, Kalyanakrishnan, et al. “Diagnosis and Treatment of Otitis Media.” Am Fam Physician, vol. 76,10 (2007): 1650-1658.

DrHouse articles are written by MDs, NPs, nutritionists and other healthcare professionals. The contents of the DrHouse site are for informational purposes only and are not a substitute for professional medical advice, diagnosis, or treatment. If you are experiencing high fever (>103F/39.4C), shortness of breath, difficulty breathing, chest pain, heart palpitations, abnormal bruising, abnormal bleeding, extreme fatigue, dizziness, new weakness or paralysis, difficulty with speech, confusion, extreme pain in any body part, or inability to remain hydrated or keep down fluids or feel you may have any other life-threatening condition, please go to the emergency department or call 911 immediately.

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