Tetracyclines
ATC code: J01AA02 (Doxycycline)
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.
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.
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.
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.
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.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
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.
7 pairs found. Sorted from critical to minor.
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.
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.
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.
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
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.
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.
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).
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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.
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.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
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.
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.
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.
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.
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.