What are the adverse effects of Doxycycline?

Adverse Effects of Doxycycline

Doxycycline has numerous adverse effects, with gastrointestinal disturbances being most common, followed by photosensitivity reactions, and less frequently serious effects including hepatotoxicity, hypersensitivity reactions, and esophageal ulcerations. 1, 2

Common Adverse Effects

Gastrointestinal Effects

• Nausea, vomiting, diarrhea, dysphagia
• Anorexia, epigastric distress
• Glossitis, black hairy tongue
• Enterocolitis
• Inflammatory lesions with Candidal overgrowth in anogenital region 1, 2

Gastrointestinal side effects are significantly more common:

• In patients ≥50 years old (16% vs 2.9% in younger patients) 3
• With higher doses (200 mg/day vs 100 mg/day) 3
• When taken without adequate fluid or immediately before lying down 4

Dermatological Effects

• Photosensitivity (increased risk of sunburn and skin reactions)
• Maculopapular and erythematous rashes
• Exfoliative dermatitis
• Onycholysis and nail discoloration 1

Serious Adverse Effects

Severe Dermatological Reactions

• Toxic epidermal necrolysis
• Stevens-Johnson syndrome
• Erythema multiforme 1, 2

Gastrointestinal Complications

• Esophagitis and esophageal ulcerations (especially when taken with insufficient water or before lying down) 2, 4
• Hepatotoxicity (rare but serious): hepatitis, jaundice, hepatic failure 1, 5

Hypersensitivity Reactions

• Urticaria, angioneurotic edema
• Anaphylaxis, anaphylactoid purpura
• Serum sickness-like reactions (fever, rash, arthralgia)
• Pericarditis
• Exacerbation of systemic lupus erythematosus 1, 2

Hematological Effects

• Hemolytic anemia
• Thrombocytopenia, thrombocytopenic purpura
• Neutropenia, eosinophilia 1, 2

Neurological Effects

• Benign intracranial hypertension (pseudotumor cerebri)
• Bulging fontanels in infants
• Headache, dizziness 1, 2

Renal Effects

• Rise in blood urea nitrogen (dose-related)
• Renal dysfunction (lower risk with doxycycline than with other tetracyclines) 1

Special Considerations

Pregnancy and Pediatric Use

• Pregnancy Category D: contraindicated in pregnancy 1, 2
• Contraindicated in children under 8 years due to permanent teeth discoloration and enamel hypoplasia 1
• Distributed into breast milk; discontinue nursing or the drug 1, 2

Drug Interactions

• Reduced absorption with antacids containing aluminum, calcium, or magnesium
• Reduced absorption with iron-containing preparations
• Reduced effectiveness of oral contraceptives
• Interaction with oral anticoagulants (may require downward adjustment)
• Reduced serum levels in alcoholic patients 1, 2

Minimizing Adverse Effects

Strategies to Reduce GI Side Effects

• Take with food and adequate fluids
• Remain upright for at least 1 hour after taking the medication
• Consider enteric-coated formulations, which have shown lower rates of GI side effects (43% vs 66% with standard formulations) 6

Monitoring Recommendations

• Routine toxicity monitoring tests (FBC, U&Es, LFTs) should be performed intermittently throughout treatment 1, 5
• In long-term therapy, periodic laboratory evaluation of hematopoietic, renal, and hepatic systems 2

Discontinuation Rates

• Overall discontinuation rate due to adverse effects is relatively low (2.6%) in long-term use 3
• Meta-analysis shows participants were more likely to be unenrolled from clinical trials due to adverse events in the doxycycline group compared to placebo 1, 7

Despite these potential adverse effects, doxycycline is generally considered safe, with most side effects being mild to moderate in severity, and serious adverse events are rare 7, 8.