What are the potential adverse effects of tetracycline, especially in patients with pre-existing medical conditions, such as impaired renal function or in pregnant women, or in children under 8 years old?

Tetracycline Adverse Effects

Tetracycline causes permanent tooth discoloration and enamel hypoplasia during tooth development, is contraindicated in pregnancy (Category D), and should not be used in children under 8 years of age unless other drugs are ineffective or contraindicated. 1, 2

Critical Contraindications and High-Risk Populations

Children Under 8 Years

• Permanent tooth discoloration (yellow-gray-brown) occurs during tooth development (last half of pregnancy through age 8), with this adverse reaction more common during long-term use but observed even with repeated short-term courses 1, 3
• Enamel hypoplasia has been documented 1, 4
• Skeletal development impairment: tetracyclines form stable calcium complexes in bone-forming tissue, causing decreased fibula growth rate in premature infants (reversible upon discontinuation) 4, 3
• Should not be used unless benefits clearly outweigh risks and other appropriate drugs are ineffective or contraindicated 1

Pregnancy and Lactation

• Pregnancy Category D: tetracyclines cross the placenta, are found in fetal tissues, and cause fetal harm including retardation of skeletal development and embryotoxicity 1, 4
• Fatal hepatotoxicity has occurred in pregnant women receiving tetracyclines 3, 5
• Distributed into breast milk: discontinue nursing or the drug 1
• For life-threatening infections (e.g., Rocky Mountain spotted fever, anthrax), short-term use (7-14 days) before six months of gestation may be considered as adverse effects on teeth and bones are dose-related 1

Renal Impairment

• Dose-related rise in blood urea nitrogen (BUN) occurs due to anti-anabolic action 1, 4
• In significantly impaired renal function, higher serum levels lead to azotemia, hyperphosphatemia, and acidosis 4, 3
• Total daily dosage should not exceed 200 mg in 24 hours when renal impairment exists 4
• Monitor creatinine and BUN; even usual doses may lead to systemic accumulation and possible liver toxicity 4, 3

Common Adverse Effects

Gastrointestinal (Most Frequent)

• Anorexia, nausea, epigastric distress, vomiting, diarrhea 1, 6, 5
• Glossitis, black hairy tongue, dysphagia 1
• Esophagitis and esophageal ulceration: take with full glass of water to reduce risk 1, 7
• Inflammatory lesions with Candidal overgrowth in oral and anogenital regions 1
• Clostridium difficile-associated diarrhea (CDAD): ranges from mild diarrhea to fatal colitis; must be considered in all patients with diarrhea following tetracycline use 4, 3

Dermatologic

• Photosensitivity (exaggerated sunburn reaction) is well-recognized and occurs throughout entire treatment duration 1, 8, 3, 6
• Patients should avoid prolonged sun exposure, use broad-spectrum sunscreens, and consider taking medication in evening to minimize peak drug levels during daytime 8
• Discontinue treatment at first evidence of skin erythema 3
• Maculopapular and erythematous rashes, exfoliative dermatitis 1
• Onycholysis and nail discoloration 1

Hepatotoxicity

• Hepatotoxicity and liver failure can occur 1, 6
• Fatal hepatic failure has been reported, particularly in pregnant women receiving high-dose intravenous tetracycline 1, 5
• Periodic liver function tests recommended for long-term therapy 7, 3

Serious and Life-Threatening Adverse Effects

Intracranial Hypertension (Pseudotumor Cerebri)

• Clinical manifestations: headache, blurred vision, diplopia, vision loss; papilledema on fundoscopy 4, 3
• Women of childbearing age who are overweight or have history of intracranial hypertension are at greater risk 4, 3
• Avoid concomitant use with isotretinoin as it also causes pseudotumor cerebri 4, 3
• Although typically resolves after discontinuation, permanent visual loss is possible 4, 3
• Prompt ophthalmologic evaluation warranted if visual disturbance occurs 4, 3
• Intracranial pressure can remain elevated for weeks after drug cessation; monitor until stabilized 4, 3

Hypersensitivity Reactions

• Urticaria, angioneurotic edema, anaphylaxis/anaphylactoid reaction (including shock and fatalities) 1
• Anaphylactoid purpura, serum sickness-like reactions 1, 3
• Pericarditis, myocarditis 1
• Exacerbation of systemic lupus erythematosus, transient lupus-like syndrome 1

Hematologic

• Hemolytic anemia, thrombocytopenia, neutropenia, eosinophilia 1
• Agranulocytosis, leukopenia, pancytopenia 1
• Bone marrow suppression (dose-related) 6

Central Nervous System

• Light-headedness, dizziness, vertigo: caution patients about driving vehicles or using hazardous machinery 4
• Symptoms may disappear during therapy and usually resolve rapidly when drug discontinued 4
• Convulsions, hypesthesia, paresthesia, sedation 1
• Bulging fontanels in infants and benign intracranial hypertension in adults 1

Respiratory

• Bronchospasm, exacerbation of asthma, pneumonitis 1

Musculoskeletal

• Arthralgia, arthritis, bone discoloration, myalgia, joint stiffness and swelling 1
• May cause myasthenia gravis exacerbation due to potential for weak neuromuscular blockade 7

Drug Interactions

Major Interactions

• Antacids (aluminum, calcium, magnesium-containing): reduce absorption 1
• Oral anticoagulants: tetracyclines potentiate warfarin effect 1, 2, 6
• Hormonal contraceptives: may decrease effectiveness 1, 2
• Iron-containing preparations: reduce tetracycline absorption 1
• Methoxyflurane: increased risk of nephrotoxicity 1
• Penicillins: tetracyclines may interfere with bactericidal action 1

Monitoring Recommendations

Long-Term Therapy

• Perform periodic laboratory evaluation: complete blood count, renal function (creatinine, BUN), liver function tests 7, 3
• Monitor for signs of superinfection, particularly oral and anogenital candidiasis 6
• Baseline and periodic liver function tests essential, especially in patients with underlying liver disease 7

Clinical Pitfalls to Avoid

• Do not use as monotherapy for acne treatment 1
• Never prescribe to children under 8 years unless absolutely necessary and other drugs ineffective 1, 2
• Avoid in pregnancy unless life-threatening infection where benefits outweigh risks 1
• Do not combine with isotretinoin due to additive risk of intracranial hypertension 4, 3
• Counsel all patients about photosensitivity before initiating therapy 8, 3
• Reduce dose in renal impairment to avoid accumulation and hepatotoxicity 4, 3