Doxycycline
Broad-spectrum tetracycline antibiotic for bacterial and atypical infections
Doxycycline is a second-generation semisynthetic tetracycline antibiotic that has been in clinical use since the 1960s. It is characterised by superior pharmacokinetics compared with earlier tetracyclines: nearly complete oral bioavailability, a long half-life of 18 to 22 hours allowing once or twice daily dosing, and excellent tissue penetration. Doxycycline is among the most versatile antibiotics available and covers a uniquely broad spectrum including atypical bacteria, intracellular pathogens, rickettsiae, and several protozoal parasites.
Doxycycline is available as tablets, capsules, and as an intravenous formulation. It is the drug of choice for conditions including Lyme disease, chlamydial infections, rickettsiosis, brucellosis, and malaria prophylaxis. In dermatology, low-dose doxycycline is widely used for acne and rosacea. It is also an important alternative antibiotic for patients with penicillin allergy.
Mechanism of Action
Doxycycline inhibits bacterial protein synthesis by binding reversibly to the 30S ribosomal subunit, specifically to the 16S rRNA component. This binding blocks the attachment of aminoacyl-tRNA to the mRNA-ribosome complex, preventing the addition of new amino acids to the growing polypeptide chain. The result is inhibition of protein synthesis and bacteriostatic activity. Doxycycline enters gram-negative bacteria via outer membrane porins and is actively concentrated inside susceptible cells by an energy-dependent transport system.
Doxycycline's effectiveness against intracellular bacteria such as Chlamydia, Rickettsia, Coxiella, and Anaplasma relates to its ability to penetrate eukaryotic host cells and reach intracellular compartments where these pathogens reside. This property, combined with its excellent oral bioavailability and tissue distribution, makes it particularly valuable for these infections.
Indications
- Lyme disease (Borrelia burgdorferi): Drug of choice for early localised and early disseminated disease in adults; erythema migrans, early neuroborreliosis
- Sexually transmitted infections: Chlamydia trachomatis (urogenital chlamydiosis, lymphogranuloma venereum), Mycoplasma genitalium (second-line)
- Rickettsioses: Rocky Mountain spotted fever, Mediterranean spotted fever, epidemic typhus — doxycycline is the drug of choice including in children when benefits outweigh risks
- Respiratory tract infections: Community-acquired pneumonia caused by atypical pathogens (Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella); alternative in penicillin allergy
- Acne and rosacea: Low-dose doxycycline (subantimicrobial dose 40 mg daily or standard 50 to 100 mg) for moderate to severe inflammatory acne and rosacea
- Malaria prophylaxis: In areas with chloroquine-resistant Plasmodium falciparum
- Brucellosis: In combination with rifampicin
- Pelvic inflammatory disease: Component of combination regimens per guideline recommendations
Dosage and Administration
Standard infections: 200 mg loading dose on day 1, then 100 mg once daily (or 100 mg twice daily for severe infections). Severe infections: 100 mg twice daily throughout. Acne: 50 to 100 mg once daily; subantimicrobial dose (40 mg once daily modified-release) for rosacea. Malaria prophylaxis: 100 mg once daily starting 1 to 2 days before travel, during stay, and for 4 weeks after return.
Doxycycline should be taken with a full glass of water and in an upright position to prevent oesophageal irritation and pill-induced oesophagitis. It can be taken with food or milk to reduce nausea — unlike other tetracyclines, doxycycline's absorption is only minimally affected by food. It should not be taken with dairy products, antacids, or iron supplements within 2 hours due to chelation-mediated reduced absorption.
Side Effects
Common: Nausea and gastrointestinal discomfort, oesophageal irritation if not taken correctly with sufficient fluid. Photosensitivity — increased sensitivity to UV radiation causing sunburn-like reactions; sunscreen and protective clothing essential.
Occasional: Vaginal candidiasis and oral candidiasis (superinfection due to disruption of normal flora), skin rash, headache, visual disturbances including benign intracranial hypertension (pseudotumour cerebri) — rare but requires discontinuation.
Permanent dental and bone effects in children: Doxycycline causes yellow-grey-brown discolouration of developing teeth and impairs bone development. It is generally contraindicated in children under 8 years and in pregnancy, though current guidelines allow short courses in younger children when the benefit outweighs the risk (e.g. rickettsiosis).
Interactions
- Antacids (aluminium, magnesium, calcium), iron supplements, bismuth, and zinc: Form insoluble chelates with doxycycline, markedly reducing absorption; administer doxycycline at least 2 hours before or 4 hours after these agents
- Anticoagulants (warfarin): Doxycycline may enhance anticoagulant effects by affecting gut flora; INR monitoring recommended
- Retinoids (isotretinoin, acitretin): Combination with systemic retinoids increases the risk of benign intracranial hypertension; avoid combination
- Rifampicin, carbamazepine, phenytoin, barbiturates: Enzyme inducers accelerate doxycycline metabolism, reducing plasma levels and efficacy
- Oral contraceptives: As with other antibiotics, possible minor reduction in efficacy through altered gut flora; additional contraceptive measures recommended
- Sucralfate: Reduces doxycycline absorption; avoid concurrent use
Special Notes
Photosensitivity: This is one of the most clinically relevant side effects. Patients should use sunscreen with SPF 30 or higher, wear protective clothing, and avoid prolonged sun exposure during treatment and for 5 days after the last dose. The risk is higher in fair-skinned individuals and increases with dose.
Oesophageal irritation: Doxycycline tablets and capsules must be swallowed with at least 200 ml of water while sitting upright or standing. Never taken immediately before lying down or at bedtime without adequate fluid. Pill-induced oesophagitis can be severe and requires medical attention.
Use in children: Traditionally contraindicated under 8 years; however, doxycycline is recommended as the first-line agent for Rocky Mountain spotted fever and other rickettsial infections in children of all ages when the clinical situation warrants, as the risk of permanent dental staining from a short course is significantly lower than the mortality risk of untreated rickettsial disease.
Pregnancy: Contraindicated due to risk of dental discolouration and effects on foetal bone development. Alternative agents should be used for infections in pregnancy.
Related Topics
- Amoxicillin — Broad-spectrum penicillin antibiotic
- Azithromycin — Macrolide antibiotic for atypical and respiratory infections
- Ciprofloxacin — Fluoroquinolone antibiotic for complex infections
- All active ingredients overview
Frequently Asked Questions
Can doxycycline be taken with milk or food?
Doxycycline can be taken with food or milk to reduce stomach discomfort, and absorption is only minimally reduced compared with other tetracyclines. However, large quantities of dairy products, calcium-rich foods, or antacids should be avoided within 2 hours of dosing as calcium chelation reduces absorption significantly.
Why should you not lie down after taking doxycycline?
If a doxycycline capsule or tablet lodges in the oesophagus, it dissolves in contact with the oesophageal mucosa and causes chemical irritation that can lead to painful oesophageal ulcers. To prevent this, doxycycline should always be taken with a full glass of water while sitting upright, and the patient should remain upright for at least 30 minutes after taking it.
How long should doxycycline be taken for Lyme disease?
For early Lyme disease (erythema migrans without neurological involvement), guidelines generally recommend 10 to 14 days of doxycycline. For early neurological Lyme disease, 14 to 21 days is typical. Longer courses are sometimes used for late-stage disease, but evidence for courses beyond 28 days is limited and guidelines recommend against prolonged antibiotic therapy for post-Lyme syndrome.