Tetracycline

Tetracycline is the original oral tetracycline, used for bismuth quadruple Helicobacter pylori therapy, brucellosis, cholera, acne, rickettsial disease and chlamydial infection. It is taken four times daily and has been largely replaced by doxycycline.

Classification. Tetracycline, first generation.

Mechanism. Binds the 30S ribosomal subunit and blocks aminoacyl-tRNA attachment; bacteriostatic.

Spectrum. Rickettsia, Chlamydia, Mycoplasma, Brucella, Vibrio cholerae, Helicobacter pylori, Treponema pallidum, Borrelia and Bacillus anthracis. Resistance is common in staphylococci, streptococci, pneumococci and Enterobacterales.

Pharmacokinetics. Oral bioavailability 60 to 80%, reduced by food and dairy. Half-life 6 to 12 hours. Excreted by kidneys, so it accumulates in renal failure.

Maximum 2 g daily.

Adults, oral. 500 mg every 6 hours (or 500 mg to 1 g every 12 hours in acne).

• Helicobacter pylori bismuth quadruple therapy: tetracycline 500 mg every 6 hours with bismuth subsalicylate or subcitrate, metronidazole 500 mg every 8 hours and a proton pump inhibitor twice daily, for 14 days.
• Brucellosis: 500 mg every 6 hours for 6 weeks with streptomycin 1 g IM daily for 14 to 21 days.
• Cholera: 500 mg every 6 hours for 3 days.
• Rickettsial disease: 500 mg every 6 hours for 5 to 7 days.
• Chlamydial infection: 500 mg every 6 hours for 7 days.
• Syphilis in penicillin allergy outside pregnancy: 500 mg every 6 hours for 14 days (early) or 28 days (late).
• Acne: 500 mg every 12 hours for at least 12 weeks.

Children 8 years and over. 25 to 50 mg/kg/day divided every 6 hours; maximum 2 g daily. Cholera 12.5 mg/kg every 6 hours for 3 days.

Alternatives. Doxycycline (preferred in most settings), azithromycin, macrolides.

Contraindications. Tetracycline hypersensitivity; pregnancy; children under 8 years except in life-threatening disease; significant renal impairment.

Adverse effects. Nausea, vomiting, diarrhoea, photosensitivity, oesophagitis, candidiasis. Serious: hepatotoxicity, pancreatitis, benign intracranial hypertension, tooth discolouration and enamel hypoplasia, anti-anabolic effect worsening azotaemia, Fanconi-type syndrome with degraded (outdated) tablets, Stevens-Johnson syndrome, Clostridioides difficile infection.

Interactions. Aluminium, magnesium, calcium, iron, zinc and bismuth products reduce absorption (take tetracycline 2 hours before or 3 hours after); warfarin (INR rise); methotrexate; retinoids (intracranial hypertension); digoxin; oral typhoid vaccine; penicillins (antagonism in severe infection).

Common prescribing errors. Taking with food or dairy, using it in renal failure, prescribing outdated tablets and using it in pregnancy.

Special groups. - Pregnancy: contraindicated (maternal hepatotoxicity and foetal tooth and bone effects). Breastfeeding: avoid. - Older adults: reduce by kidney function. - Kidney impairment: avoid where possible and use doxycycline. If unavoidable: creatinine clearance 50 to 80 mL/min every 8 to 12 hours; 10 to 50 mL/min every 12 to 24 hours; under 10 mL/min every 24 hours. - Liver impairment: avoid.

Administration. Take on an empty stomach, 1 hour before or 2 hours after food, with a full glass of water, upright; avoid dairy.

Baseline and monitoring. - Baseline: pregnancy test, creatinine, liver tests, medication review. - During treatment: creatinine and liver tests in courses over 2 weeks; headache and visual symptoms.

Stop rules. Stop for jaundice, severe skin reaction, papilloedema or worsening kidney function.

Referral and escalation. Refer for treatment failure in brucellosis or H. pylori, and for hepatic or renal complications.