What are the side effects of doxycycline?

Doxycycline Side Effects

Doxycycline causes common gastrointestinal side effects (nausea, vomiting, diarrhea) and photosensitivity in most patients, with rare but serious complications including esophageal ulceration, severe skin reactions, and hepatotoxicity that require immediate recognition and management.

Common Side Effects

Gastrointestinal Effects

• Nausea, vomiting, and diarrhea are the most frequent adverse effects, occurring in approximately 15.7% of patients compared to 5.9% with placebo 1
• Dysphagia and abdominal discomfort occur commonly, particularly with standard formulations 2
• Anorexia and glossitis may develop during treatment 3
• Enteric-coated formulations significantly reduce upper GI symptoms compared to standard preparations 4

Dermatological Effects

• Photosensitivity and rash are the most common skin reactions 2
• Photosensitivity is dose-dependent and requires strict sun protection during therapy 5
• Maculopapular and erythematous rashes can occur 2, 3

Serious Side Effects Requiring Immediate Attention

Gastrointestinal Complications

• Esophagitis and esophageal ulcerations occur in approximately 1.6% of patients on long-term therapy, particularly when taken without adequate water or before lying down 6, 3
• Pseudomembranous colitis (C. difficile infection) can develop 2
• Hepatotoxicity including hepatitis, jaundice, and hepatic failure (rare but potentially fatal) 2
• Pancreatitis has been reported 2

Severe Dermatological Reactions

• Stevens-Johnson syndrome and toxic epidermal necrolysis are life-threatening conditions 2, 3
• Erythema multiforme and exfoliative dermatitis 2, 3
• Photo-onycholysis (nail separation due to photosensitivity) 2
• Dual cutaneous reactions (simultaneous phototoxicity and morbilliform eruption) can occur 7

Hematological Effects

• Hemolytic anemia 2, 3
• Thrombocytopenia and neutropenia 2, 3
• Eosinophilia 2, 3
• Porphyria 2

Neurological Complications

• Benign intracranial hypertension (pseudotumor cerebri) presents with headache and visual changes 2, 3
• Bulging fontanels in infants 2, 3

Other Serious Effects

• Anaphylaxis and anaphylactoid reactions (including shock and fatalities) 2, 3
• Pericarditis and exacerbation of systemic lupus erythematosus 2, 3
• Renal dysfunction (though lower risk than other tetracyclines) 2
• Serum sickness 2, 3

Risk Factors for Increased Adverse Effects

• Age ≥50 years significantly increases GI adverse effects (8/50 vs. 4/139 in younger patients, p=0.003) 6
• Higher doses (200 mg/day vs. 100 mg/day) substantially increase GI complications (12/93 vs. 0/96, p<0.001) 6
• Long-term use (>1 month) increases risk of esophagitis and other GI effects 6

Critical Prevention Strategies

Administration Guidelines

• Take with a full glass of water (at least 200ml) while sitting or standing to prevent esophageal ulceration 2
• Take during meals to reduce GI upset 2
• Never take immediately before lying down or bedtime 3
• Remain upright for at least 1 hour after administration 4

Drug Interactions Affecting Absorption

• Separate from antacids containing aluminum, calcium, or magnesium by 2-3 hours 2
• Avoid concurrent iron-containing preparations 2
• Separate from caffeine and vitamin C by 1-2 hours as they reduce bioavailability 8

Sun Protection

• Avoid extensive sunlight or UV irradiation throughout treatment 2
• Use broad-spectrum sunscreen and protective clothing 1

Monitoring Requirements

• Intermittent monitoring of CBC, renal function (U&Es), and liver function tests (LFTs) throughout treatment 2
• Drug levels do not require routine measurement 2

Absolute Contraindications

• Hypersensitivity to doxycycline or other tetracyclines 2
• Children under 12 years of age due to permanent tooth discoloration and enamel hypoplasia 2
• Pregnancy (Category D) and breastfeeding 2, 5

Special Cautions

• Hepatic impairment or concurrent hepatotoxic drugs 2
• Myasthenia gravis (risk of neuromuscular blockade) 2
• Systemic lupus erythematosus (risk of exacerbation) 2
• Porphyria 2

Common Pitfall to Avoid

The most preventable serious complication is esophageal ulceration, which occurs when patients take doxycycline capsules/tablets with insufficient water or immediately before bed. Always emphasize proper administration technique with adequate hydration and upright positioning 3, 6.