Doxycycline

Doxycycline is a broad-spectrum tetracycline given orally or intravenously, used for atypical pneumonia, rickettsial disease, brucellosis, chlamydia, syphilis in penicillin allergy, leptospirosis, cholera, malaria prophylaxis and filarial infection. It is the first-line drug for rickettsial disease at any age.

Classification. Tetracycline, second generation.

Mechanism. Binds the 30S ribosomal subunit and blocks aminoacyl-tRNA attachment; bacteriostatic. It also has anti-inflammatory and anti-Wolbachia activity.

Spectrum. Rickettsia, Orientia, Coxiella, Chlamydia, Mycoplasma, Legionella, Brucella, Borrelia, Leptospira, Vibrio cholerae, Treponema pallidum, Bacillus anthracis, Yersinia pestis, MRSA (many strains), Wolbachia and Plasmodium (as adjunct). Pneumococcal and streptococcal resistance is common. Not reliable against Enterobacterales or Pseudomonas.

Pharmacokinetics. Oral bioavailability over 90%, slightly reduced by dairy. Half-life 16 to 22 hours. Protein binding 80 to 90%. Eliminated by non-renal routes (gut and bile), so no adjustment in renal failure.

Maximum 300 mg daily in adults in usual indications.

Adults, oral or IV (loading 200 mg on day 1 in most infections, then 100 mg every 12 hours).

• Community-acquired pneumonia, atypical cover: 100 mg every 12 hours for 5 to 7 days.
• Rickettsial infection (scrub typhus, tick typhus, murine typhus): 100 mg every 12 hours until afebrile for at least 3 days (usually 5 to 7 days); Q fever 14 days.
• Brucellosis: 100 mg every 12 hours for 6 weeks with rifampicin 600 to 900 mg daily, or with streptomycin 1 g IM daily for 14 to 21 days.
• Leptospirosis: 100 mg every 12 hours for 7 days; prophylaxis 200 mg once weekly.
• Urogenital chlamydia, non-gonococcal urethritis: 100 mg every 12 hours for 7 days; lymphogranuloma venereum 21 days.
• Pelvic inflammatory disease: 100 mg every 12 hours for 14 days, with ceftriaxone and metronidazole.
• Syphilis in penicillin allergy outside pregnancy: 100 mg every 12 hours for 14 days (early) or 28 days (late latent).
• Cholera: 300 mg as a single dose.
• Early Lyme disease: 100 mg every 12 hours for 10 to 21 days.
• Malaria prophylaxis: 100 mg once daily, starting 1 to 2 days before travel, continued during and for 4 weeks after leaving the area.
• Malaria treatment adjunct: 100 mg every 12 hours for 7 days with quinine or artesunate.
• Lymphatic filariasis and onchocerciasis (anti-Wolbachia): 200 mg once daily for 4 to 6 weeks.
• MRSA skin and soft tissue infection: 100 mg every 12 hours for 5 to 10 days.
• Post-exposure prophylaxis after condomless sex in selected groups: 200 mg as a single dose within 72 hours.

Children 8 years and over. 2.2 mg/kg every 12 hours (maximum 100 mg a dose), with 4.4 mg/kg (maximum 200 mg) on day 1. In rickettsial disease it is used at any age because the benefit outweighs dental risk in short courses (21 days or less).

Alternatives. Azithromycin, macrolides, chloramphenicol (rickettsial disease in pregnancy), fluoroquinolones.

Contraindications. Tetracycline hypersensitivity; severe hepatic failure.

Adverse effects. Nausea, vomiting, photosensitivity, oesophagitis and oesophageal ulcer, candidiasis, diarrhoea. Serious: benign intracranial hypertension, hepatotoxicity, pancreatitis, DRESS, Stevens-Johnson syndrome, Clostridioides difficile infection, thrombophlebitis with IV use, permanent tooth staining and enamel hypoplasia in young children with repeated courses.

Interactions.

• Aluminium, magnesium, calcium, iron, zinc and bismuth products and sucralfate reduce absorption: take doxycycline at least 2 hours before or 4 hours after them.
• Rifampicin, carbamazepine, phenytoin and barbiturates shorten the half-life.
• Warfarin (INR rise), isotretinoin and other retinoids (intracranial hypertension), methotrexate, ciclosporin, oral typhoid vaccine.

Common prescribing errors. Taking tablets lying down or without a full glass of water, giving with iron or antacids, omitting the loading dose in severe infection, and withholding it in suspected rickettsial disease in children.

Special groups.

• Pregnancy: avoid (foetal tooth and bone effects). Use only in life-threatening rickettsial disease, anthrax or plague when no alternative exists.
• Breastfeeding: short courses of 21 days or less are acceptable.
• Older adults: usual dose.
• Kidney impairment: no adjustment.
• Liver impairment: use with caution; avoid in severe disease.
• Region: in East Africa it is central to rickettsial and brucella treatment, cholera outbreaks, malaria prophylaxis and filarial programmes. Pneumococcal resistance is common, so it is not used alone for pneumonia.

Preparation. Oral: swallow upright with a full glass of water, not at bedtime; with food if nausea. IV: reconstitute and dilute to 0.1 to 1 mg/mL and infuse over 1 to 4 hours, protected from light; not for IM or rapid IV use.

Baseline and monitoring. - Baseline: pregnancy test, medication review for cations and retinoids, liver tests in prolonged courses. - During treatment: sun protection; headache and visual symptoms (intracranial hypertension); liver tests in courses over 4 weeks.

Stop rules. Stop for severe skin reaction, papilloedema or visual change, jaundice, or persistent oesophageal pain.

Referral and escalation. Refer for suspected rickettsial disease with organ failure, neurobrucellosis, endocarditis and treatment failure.