Doxycycline

Tetracyclines

ATC code: J01AA02 (Doxycycline)

Mechanism of action

Binds the 30S ribosomal subunit and blocks aminoacyl-tRNA attachment to the A-site, inhibiting bacterial protein synthesis. Bacteriostatic. Broad spectrum: gram-positive and gram-negative organisms, atypical pathogens – Mycoplasma, Chlamydia, Legionella, and also Rickettsia, Borrelia burgdorferi, Treponema pallidum. Compared to tetracycline, it has better bioavailability and a longer half-life of 18-22 hours.

Indications

Acne vulgaris

First line

First-line systemic antibiotic for moderate-to-severe acne per 2024 guidelines. Dose is 100 mg once or twice daily for 3 months. Sub-antimicrobial dose of 40 mg modified-release (not registered in Russia) reduces inflammation without antibiotic pressure. Always combine with a topical retinoid and/or benzoyl peroxide to prevent resistance.

Sources

Chlamydial infection

First line

First-line for uncomplicated chlamydial infection alongside azithromycin. Doxycycline 100 mg twice daily for 7 days. Recent meta-analyses suggest a slight advantage over single-dose azithromycin in eradication rates. In men with chlamydial proctitis, doxycycline is preferred.

Sources

Community-acquired pneumonia

First line

Alternative to macrolides for atypical community-acquired pneumonia. Active against Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella. Per /ATS 2019, doxycycline is an outpatient CAP monotherapy option in patients without comorbidities when a macrolide is not suitable. Dose is 100 mg twice daily.

Sources

Lyme disease (borreliosis)

First line

Drug of choice for Lyme disease per // 2020. For early localized disease (erythema migrans), prescribe 100 mg twice daily for 10-21 days. For early disseminated disease without CNS involvement, the same regimen for 14-21 days. Doxycycline is the only oral antibiotic effective in neuroborreliosis without meningitis.

Sources

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Acute viral upper respiratory infection

Not recommended

Doxycycline is used for upper respiratory infections, influenza and mild COVID-19 without confirmed bacterial coinfection. 2024 AWaRe and NG191 2020 do not recommend antibiotics in URIs. The PRINCIPLE 2021 (Butler) trial did not show doxycycline benefit in outpatient COVID-19. Teratogenicity ( category D) and photosensitivity in children under 8 add risk.

Sources

Practical notes

Timing and administration

Take with food, swallowed with a full glass of water. Remain upright for at least 30 minutes after the dose – doxycycline causes esophageal erosions on mucosal contact. Taking the evening dose right before bed is a common cause of esophagitis. Avoid milk: although dairy affects doxycycline less than tetracycline, spacing is still advisable.

Special situations

Photosensitivity is the main practical side effect. Patients should avoid direct sunlight and use SPF 50+. Risk is higher in summer months. Antacids, iron, calcium, and magnesium chelate doxycycline and reduce absorption – separate dosing by 2-3 hours. Long courses in children under 8 are restricted due to the historical risk of teeth staining; however, since 2018 the accepts short courses (up to 21 days) at any age for rickettsial diseases, neuroborreliosis, and other life-threatening infections – the meta-analysis by Cross R et al. (Pediatrics. 2016;137(3):e20153447) found no clinically significant tooth discoloration with short courses.

Drug–drug interactions

7 pairs found. Sorted from critical to minor.

Major

Carbamazepine

Antiepileptics. Carboxamide derivatives

Mechanism

Carbamazepine induces CYP3A4 and accelerates hepatic doxycycline metabolism. Doxycycline half-life shortens from 16 to 7 hours; plasma levels fall.

Symptoms

The patient feels nothing. Risk of subtherapeutic antimicrobial concentrations and treatment failure rises – particularly with pathogens at the susceptibility breakpoint.

Management

Increase doxycycline to 200 mg twice daily during the course (instead of standard 100 mg twice daily). Alternative antibiotics without induction-driven loss: a cephalosporin, amoxicillin, azithromycin. Alternative anticonvulsants without induction: levetiracetam, lamotrigine.

Sources

FDA: Vibramycin (doxycycline) prescribing information (2008)

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Major

isotretinoin

Systemic retinoid (vitamin A derivative)

Mechanism

Both drugs cause benign intracranial hypertension (pseudotumor cerebri). Additive risk with classic presentation: headache, diplopia, visual disturbance, optic disc oedema.

Symptoms

Persistent pressing headache (not relieved by analgesics), diplopia, transient visual disturbances, tinnitus. Examination: optic disc oedema, blind spot enlargement. Symptoms appear several weeks into combination.

Management

The combination is not prescribed. Alternative antibiotic for acne on isotretinoin: azithromycin (short course) or topical retinoids. If headache with diplopia appears, stop both drugs immediately and refer to ophthalmology.

Sources

FDA: Accutane (isotretinoin) boxed warning (2010)

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Moderate

Amoxicillin

Penicillins with extended spectrum

Mechanism

A bacteriostatic agent (doxycycline) suppresses the bactericidal action of a beta-lactam (amoxicillin), which requires active bacterial division. Antibacterial efficacy drops.

Symptoms

Persistent fever, infection symptoms, and inflammation markers 48–72 hours after starting therapy. Resistant strain selection possible.

Management

Avoid the combination — choose a single antibiotic based on pathogen and infection site. For mixed infections (e.g. aspiration pneumonia), prefer switching to amoxicillin-clavulanate (broader spectrum) or a cephalosporin with metronidazole. For Lyme disease, use doxycycline monotherapy; for respiratory infections with confirmed sensitivity, amoxicillin.

Sources

FDA: Bactrim (sulfamethoxazole and trimethoprim) prescribing information (2013)

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Minor

Calcium carbonate

Mineral supplements. Calcium

Mechanism

Doxycycline forms non-absorbable chelates with calcium in the gut (and with other polyvalent cations — magnesium, iron, aluminium). Doxycycline bioavailability falls by 50–80%.

Symptoms

Persistent infection symptoms 48–72 hours after antibiotic start, risk of clinical failure.

Management

Take doxycycline 2 hours before or 6 hours after calcium carbonate. Apply the same interval for iron, magnesium, zinc, and aluminium-containing antacids. If timing separation is impossible, choose an alternative antibiotic (amoxicillin, a cephalosporin).

Sources

Pair details →

Minor

Estradiol

Estrogens — natural and semisynthetic

Mechanism

Doxycycline does not induce CYP3A4 and does not affect oestradiol metabolism. No clinically significant reduction in menopausal hormone therapy efficacy has been reported.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

No dose adjustment needed. In women on menopausal hormone therapy, doxycycline is used without special precautions for infections requiring it.

Sources

ACOG: Use of Hormonal Contraception in Women With Coexisting Medical Conditions, Practice Bulletin No. 206 (2018)

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Minor

Ethinylestradiol

Estrogens. Natural and semisynthetic estrogens, plain

Mechanism

Doxycycline does not affect hepatic ethinylestradiol metabolism. The historical theory of reduced COC efficacy via suppression of enterohepatic recirculation is rejected by meta-analyses.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

Additional contraception during short doxycycline courses is not needed. For long-term therapy (e.g. acne, Lyme disease), no adjustment either.

Sources

ACOG: Use of Hormonal Contraception in Women With Coexisting Medical Conditions, Practice Bulletin No. 206 (2018)

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Minor

Iron oral (salts: sulfate, bisglycinate, fumarate, gluconate, polymaltose; heme iron polypeptide, lactoferrin)

Oral iron preparations; antianaemic agents

Mechanism

Iron forms non-absorbable chelates with tetracyclines in the gut (as with the doxycycline-calcium pair). Doxycycline bioavailability falls by 50–80%.

Symptoms

Persistent infection symptoms 48–72 hours after antibiotic start, risk of clinical failure.

Management

Take doxycycline 2 hours before or 6 hours after iron supplements. Same interval applies to calcium, magnesium, zinc, and aluminium-containing antacids. If timing separation is impossible (e.g. severe iron deficiency), choose an alternative antibiotic (amoxicillin, a cephalosporin).

Sources

FDA: Vibramycin (doxycycline) prescribing information (2014)

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Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMA

Spanish Medicines Information Centre (CIMA)

Label dated: 12/12/2025

FDA / DailyMed

FDA — DailyMed Drug Labels

Label dated: 05/01/2026

Safety

Contraindications

Long courses in children under 8 (short courses up to 21 days for rickettsial disease or neuroborreliosis are acceptable per AAP 2018)
Pregnancy
Hypersensitivity to tetracyclines
Severe hepatic impairment

Serious adverse effects

Benign intracranial hypertension (pseudotumor cerebri) – rare
Clostridioides difficile-associated diarrhea
Hepatotoxicity (at high doses)
Teeth discoloration in children – irreversible

Common adverse effects

Nausea, diarrhea
Photosensitivity
Esophagitis, esophageal ulceration (with improper administration)
Vaginal candidiasis

PregnancyFDA D

FDA pregnancy categories were retired in 2015 under PLLR (historically category D). Tetracyclines cross the placenta and accumulate in fetal bones and teeth in the second and third trimesters. Avoided during pregnancy. In life-threatening rickettsial disease, doxycycline may be used in pregnancy after specialist consultation – benefit outweighs the theoretical risk.

Breastfeeding

Passes into breast milk in small amounts. Calcium in milk binds doxycycline, reducing its bioavailability to the infant. Per LactMed, short-term use is acceptable, but prolonged courses during breastfeeding are not recommended.

Peak milk concentration: 0.96 mg/L

Calculate RID Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Frequently asked

What is Doxycycline used for?

Doxycycline is evaluated for the following indications with varying evidence strength: Community-acquired pneumonia (evidence tier A), Acne vulgaris (evidence tier A), Lyme disease (borreliosis) (evidence tier A). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Doxycycline?

Common side effects of Doxycycline (≥ 1 in 100): Nausea, diarrhea, Photosensitivity, Esophagitis, esophageal ulceration (with improper administration), Vaginal candidiasis. See the Safety section for uncommon and serious reactions.

Is Doxycycline safe during pregnancy?

FDA category D. FDA pregnancy categories were retired in 2015 under PLLR (historically category D). Tetracyclines cross the placenta and accumulate in fetal bones and teeth in the second and third trimesters. Avoided during pregnancy. In life-threatening rickettsial disease, doxycycline may be used in pregnancy after specialist consultation – benefit outweighs the theoretical risk.

Is Doxycycline compatible with breastfeeding?

Who should not take Doxycycline?

Doxycycline is contraindicated in: Long courses in children under 8 (short courses up to 21 days for rickettsial disease or neuroborreliosis are acceptable per AAP 2018); Pregnancy; Hypersensitivity to tetracyclines; Severe hepatic impairment. Full list in the Safety section.

Mechanism of action

Practical notes

Timing and administration

Special situations

Drug–drug interactions

7 pairs found. Sorted from critical to minor.

Major

Carbamazepine

Antiepileptics. Carboxamide derivatives

Mechanism

Carbamazepine induces CYP3A4 and accelerates hepatic doxycycline metabolism. Doxycycline half-life shortens from 16 to 7 hours; plasma levels fall.

Symptoms

The patient feels nothing. Risk of subtherapeutic antimicrobial concentrations and treatment failure rises – particularly with pathogens at the susceptibility breakpoint.

Management

Sources

FDA: Vibramycin (doxycycline) prescribing information (2008)

Pair details →

Major

isotretinoin

Systemic retinoid (vitamin A derivative)

Mechanism

Both drugs cause benign intracranial hypertension (pseudotumor cerebri). Additive risk with classic presentation: headache, diplopia, visual disturbance, optic disc oedema.

Symptoms

Management

Sources

FDA: Accutane (isotretinoin) boxed warning (2010)

Pair details →

Moderate

Amoxicillin

Penicillins with extended spectrum

Mechanism

A bacteriostatic agent (doxycycline) suppresses the bactericidal action of a beta-lactam (amoxicillin), which requires active bacterial division. Antibacterial efficacy drops.

Symptoms

Persistent fever, infection symptoms, and inflammation markers 48–72 hours after starting therapy. Resistant strain selection possible.

Management

Sources

FDA: Bactrim (sulfamethoxazole and trimethoprim) prescribing information (2013)

Pair details →

Minor

Calcium carbonate

Mineral supplements. Calcium

Mechanism

Doxycycline forms non-absorbable chelates with calcium in the gut (and with other polyvalent cations — magnesium, iron, aluminium). Doxycycline bioavailability falls by 50–80%.

Symptoms

Persistent infection symptoms 48–72 hours after antibiotic start, risk of clinical failure.

Management

Sources

Pair details →

Minor

Estradiol

Estrogens — natural and semisynthetic

Mechanism

Doxycycline does not induce CYP3A4 and does not affect oestradiol metabolism. No clinically significant reduction in menopausal hormone therapy efficacy has been reported.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

No dose adjustment needed. In women on menopausal hormone therapy, doxycycline is used without special precautions for infections requiring it.

Sources

ACOG: Use of Hormonal Contraception in Women With Coexisting Medical Conditions, Practice Bulletin No. 206 (2018)

Pair details →

Minor

Ethinylestradiol

Estrogens. Natural and semisynthetic estrogens, plain

Mechanism

Doxycycline does not affect hepatic ethinylestradiol metabolism. The historical theory of reduced COC efficacy via suppression of enterohepatic recirculation is rejected by meta-analyses.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

Additional contraception during short doxycycline courses is not needed. For long-term therapy (e.g. acne, Lyme disease), no adjustment either.

Sources

ACOG: Use of Hormonal Contraception in Women With Coexisting Medical Conditions, Practice Bulletin No. 206 (2018)

Pair details →

Minor

Iron oral (salts: sulfate, bisglycinate, fumarate, gluconate, polymaltose; heme iron polypeptide, lactoferrin)

Oral iron preparations; antianaemic agents

Mechanism

Iron forms non-absorbable chelates with tetracyclines in the gut (as with the doxycycline-calcium pair). Doxycycline bioavailability falls by 50–80%.

Symptoms

Persistent infection symptoms 48–72 hours after antibiotic start, risk of clinical failure.

Management

Sources

FDA: Vibramycin (doxycycline) prescribing information (2014)

Pair details →

Safety

Contraindications

Long courses in children under 8 (short courses up to 21 days for rickettsial disease or neuroborreliosis are acceptable per AAP 2018)
Pregnancy
Hypersensitivity to tetracyclines
Severe hepatic impairment

Serious adverse effects

Benign intracranial hypertension (pseudotumor cerebri) – rare
Clostridioides difficile-associated diarrhea
Hepatotoxicity (at high doses)
Teeth discoloration in children – irreversible

Common adverse effects

Nausea, diarrhea
Photosensitivity
Esophagitis, esophageal ulceration (with improper administration)
Vaginal candidiasis

PregnancyFDA D

Breastfeeding

Peak milk concentration: 0.96 mg/L

Calculate RID Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Frequently asked

What is Doxycycline used for?

What are the side effects of Doxycycline?

Is Doxycycline safe during pregnancy?

Is Doxycycline compatible with breastfeeding?

Who should not take Doxycycline?